bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of TRAF6 in a large multiancestral lupus cohort
Authors: Namjou Bahram , Choi Chan‐Bum , Harley Isaac T. W. , Alarcón‐Riquelme Marta E. ,   BIOLUPUS Network, Kelly Jennifer A. , Glenn Stuart B. , Ojwang Joshua O. , Adler Adam , Kim Kwangwoo , Gallant Caroline J. , Boackle Susan A. , Criswell Lindsey A. , Kimberly Robert P. , Brown Elizabeth E. , Edberg Jeffrey , Alarcón Graciela S. , Stevens Anne M. , Jacob Chaim O. , Gilkeson Gary S. , Kamen Diane L. , Tsao Betty P. , Anaya Juan‐Manuel , Kim Eun‐Mi , Park So‐Yeon , Sung Yoon‐Kyoung , Guthridge Joel M. , Merrill Joan T. , Petri Michelle , Ramsey‐Goldman Rosalind , Vilá Luis M. , Niewold Timothy B. , Martin Javier , Pons‐Estel Bernardo A. ,   Genoma en Lupus Network, Vyse Timothy J. , Freedman Barry I. , Moser Kathy L. , Gaffney Patrick M. , Williams Adrienne H. , Comeau Mary E. , Reveille John D. , Kang Changwon , James Judith A. , Scofield R. Hal , Langefeld Carl D. , Kaufman Kenneth M. , Harley John B. , Bae Sang‐Cheol 
Published: January 2012

AbstractObjectiveSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well as environmental factors. We undertook to study the role of TRAF6 as a candidate gene for SLE, since it plays a major role in several signaling pathways that are important for immunity and organ development.MethodsFifteen single‐nucleotide polymorphisms (SNPs) across TRAF6 were evaluated in 7,490 SLE patients and 6,780 control subjects from different ancestries. Population‐based case–control association analyses and meta‐analyses were performed. P values, false discovery rate q values, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.ResultsEvidence of associations was detected in multiple SNPs. The best overall P values were obtained for SNPs rs5030437 and rs4755453 (P = 7.85 × 10−5 and P = 4.73 × 10−5, respectively) without significant heterogeneity among populations (P = 0.67 and P = 0.50, respectively, in Q statistic). In addition, SNP rs540386, which was previously reported to be associated with rheumatoid arthritis (RA), was found to be in linkage disequilibrium with these 2 SNPs (r2 = 0.95) and demonstrated evidence of association with SLE in the same direction (meta‐analysis P = 9.15 × 10−4, OR 0.89 [95% CI 0.83–0.95]). The presence of thrombocytopenia improved the overall results in different populations (meta‐analysis P = 1.99 × 10−6, OR 0.57 [95% CI 0.45–0.72], for rs5030470). Finally, evidence of family‐based association in 34 African American pedigrees with the presence of thrombocytopenia was detected in 1 available SNP (rs5030437) with a Z score magnitude of 2.28 (P = 0.02) under a dominant model.ConclusionOur data indicate the presence of association of TRAF6 with SLE, consistent with the previous report of association with RA. These data provide further support for the involvement of TRAF6 in the pathogenesis of autoimmunity.
Inhibiting calcineurin activity under physiologic tonicity elevates anabolic but suppresses catabolic chondrocyte markers
Authors: van der Windt Anna E. , Haak Esther , Kops Nicole , Verhaar Jan A. N. , Weinans Harrie , Jahr Holger 
Published: January 2012

AbstractObjectiveThe physiologic interstitial tonicity of healthy articular cartilage (350–480 mOsm) is lowered to 280–350 mOsm in osteoarthritis (OA). This results in loss of tissue prestress, altered compressive behavior, and, thus, inferior tissue properties. This study was undertaken to determine whether physiologic tonicity in combination with the inhibition of calcineurin (Cn) activity by FK‐506 has synergistic effects on human articular chondrocytes and explants in vitro.MethodsOA chondrocytes and explants and non‐OA chondrocytes were cultured in cytokine‐free medium of 280 mOsm or 380 mOsm with or without Cn inhibition by FK‐506. Chondrogenic, hypertrophic, and catabolic marker expression was evaluated at the messenger RNA (mRNA), protein, and activity levels.ResultsCompared to OA chondrocytes cultured at 280 mOsm, those cultured at 380 mOsm had increased expression of mRNA for chondrogenic markers (e.g., ∼13 fold for COL2; P < 0.001), and decreased COL1 expression (∼0.5 fold, P < 0.01). Inhibiting Cn activity under physiologic tonicity further enhanced the expression of anabolic markers at the mRNA level (∼50 fold for COL2; P < 0.001, ∼2 fold for AGC1; P < 0.001, and ∼3.5 fold for SOX9; P < 0.001) and at the protein level (∼6 fold for type II collagen; P < 0.001). Cn inhibition suppressed relevant collagenases as well as hypertropic and mineralization markers at the mRNA and activity levels. Expression of aggrecanase 1 and aggrecanase 2 was not influenced by tonicity or FK‐506 alone, but the combination suppressed both, by ∼50% (P < 0.05) and ∼40% (P < 0.001), respectively. Generally, similar anabolic and antihypertrophic effects were observed in ex vivo cartilage explant cultures and non‐OA chondrocytes.ConclusionOur findings indicate that Cn at physiologic tonicity exerts a superior effect compared to physiologic tonicity or FK‐506 alone, increasing anabolic markers while suppressing hypertrophic and catabolic markers. Our data may aid in the development of improved cell‐based chondral repair and OA treatment strategies.
DNA demethylation of CD40L in CD4+ T cells from women with systemic sclerosis: A possible explanation for female susceptibility
Authors: Lian XiaoRi , Xiao Rong , Hu Xinhong , Kanekura Takuro , Jiang HongYan , Li YaPing , Wang YaoYao , Yang Yan , Zhao Ming , Lu QianJin 
Published: January 2012

AbstractObjectiveSystemic sclerosis (SSc) is an autoimmune disease with a predilection for women. The interaction between CD40 and CD154 (CD40L) is known to be involved in the development of SSc. Although CD40L is overexpressed in patients with SSc, the mechanisms leading to this overexpression are not well understood. We previously demonstrated that DNA demethylation reactivates the silent X chromosome, resulting in CD40L overexpression in healthy women. We hypothesized that CD40L up‐regulation by DNA demethylation and subsequent reactivation of the silent X chromosome in female patients with SSc explain the susceptibility of women to SSc. The aim of this study was to investigate the effect of DNA demethylation on CD40L expression in CD4+ T cells from female patients with SSc.MethodsCD40L expression in CD4+ T cells from patients with SSc and healthy control subjects was measured by flow cytometry and real‐time reverse transcription–polymerase chain reaction. Bisulfite sequencing was performed to determine the methylation status of the CD40L regulatory region.ResultsCD40L expression was significantly elevated in female patients with SSc. The methylation levels of the DNA regulatory sequences were reduced in female patients with SSc compared with healthy women, and there was a significant inverse correlation between the average methylation level and CD40L mRNA expression in female patients with SSc. In contrast, no significant difference was observed in the expression of CD40L between male patients with SSc and male control subjects. The DNA regulatory regions in both male patients and male control subjects were largely unmethylated.ConclusionDemethylation of CD40L regulatory elements on the inactive X chromosome contributes to CD40L overexpression in CD4+ T cells from female patients with SSc.
Anatomists provide the foundation for learning pathophysiology
Authors: McBride Jennifer M. , Bierer S. B. 
Published: January 2012

AbstractThe need for interdisciplinary graduate training programs which prepare students to conceptualize the application of their research in clinical settings continues to grow. Though several programs have been cultivated to address this need, demand still outweighs supply. The following describes a curriculum developed with the intent of incorporating medical knowledge into a PhD graduate training program. Development of this Molecular Medicine program by the Cleveland Clinic Lerner College of Medicine in collaboration with Case Western Reserve University was funded by the Howard Hughes Medical Institute “Med into Grad” initiative. The core curriculum of this program begins with a foundation in Human Physiology and Disease course in which anatomy faculty introduce students to a basic overview of gross anatomy structure and function. This course is followed by five fundamental basic science courses, a composite course focusing on principles of clinical and translation research, a course on laboratory techniques and three, 12‐week research rotations. In the second year of the program, students begin their dissertation research, complete their qualifying examination, and partake in an individually tailored Clinical Experience course. Interdisciplinary graduate programs like this provide another venue for faculty in anatomical sciences to help aspiring translational scientists relate basic science knowledge to human pathophysiology and health. Anat Sci Educ. © 2012 American Association of Anatomists.
Computer visualizations: Factors that influence spatial anatomy comprehension
Authors: Nguyen Ngan , Nelson Andrew J. , Wilson Timothy D. 
Published: January 2012

AbstractComputer visualizations are increasingly common in education across a range of subject disciplines, including anatomy. Despite optimism about their educational potential, students sometime have difficulty learning from these visualizations. The purpose of this study was to explore a range of factors that influence spatial anatomy comprehension before and after instruction with different computer visualizations. Three major factors were considered: (1) visualization ability (VZ) of learners, (2) dynamism of the visual display, and (3) interactivity of the system. Participants (N = 60) of differing VZs (high, low) studied a group of anatomical structures in one of three visual conditions (control, static, dynamic) and one of two interactive conditions (interactive, non‐interactive). Before and after the study phase, participants' comprehension of spatial anatomical information was assessed using a multiple‐choice spatial anatomy task (SAT) involving the mental rotation of the anatomical structures, identification of the structures in 2D cross‐sections, and localization of planes corresponding to given cross‐sections. Results indicate that VZ had a positive influence on SAT performance but instruction with different computer visualizations could modulate the effect of VZ on task performance. Anat Sci Educ. © 2012 American Association of Anatomists.
Risk factors for postoperative bleeding after thyroid surgery
Authors: Promberger R , Ott J , Kober F , Koppitsch C , Seemann R , Freissmuth M , Hermann M 
Published: January 2012

Abstract

Background
Postoperative bleeding after thyroid surgery is a feared and life-threatening complication. The aim of the study was to identify risk factors for postoperative bleeding, with special emphasis on the impact of the individual surgeon and the time to diagnosis of the complication.

Methods
Data on consecutive thyroid operations were collected prospectively in a database over 30 years and analysed retrospectively for potential risk factors for postoperative bleeding.

Results
There were 30 142 operations and postoperative bleeding occurred in 519 patients (1·7 per cent). Risk factors identified were older age (odds ratio (OR) 1·03 per year), male sex (OR 1·64), extent of resection (OR up to 1·41), bilateral procedure (OR 1·99) and operation for recurrent disease (OR 1·54). The risk of complications among individual surgeons differed by up to sevenfold. Postoperative bleeding occurred in 336 (80·6 per cent) of 417 patients within the first 6 h after surgery. Postoperative bleeding was diagnosed after 24 h in ten patients (2·4 per cent), all of whom had bilateral procedures. Nine patients required urgent tracheostomy. Three patients died, giving a mortality rate of 0·01 per cent overall and 0·6 per cent among patients who had surgery for postoperative bleeding.

Conclusion
Observation for up to 24 h is recommended for the majority of patients undergoing bilateral thyroid surgery in an endemic goitre area. Same-day discharge is feasible in selected patients, especially after a unilateral procedure. Quality improvement by continuous outcome monitoring and retraining of individual surgeons is suggested.
Supramolecular cellular filament systems: How and why do they form?
Authors: Popp David , Robinson Robert C. 
Published: January 2012

AbstractAll cells, from simple bacteria to complex human tissues, rely on extensive networks of protein fibers to help maintain their proper form and function. These filament systems usually do not operate as single filaments, but form complex suprastructures, which are essential for specific cellular functions. Here, we describe the progress in determining the architectures of molecular filamentous suprastructures, the principles leading to their formation, and the mechanisms by which they may facilitate function. The complex eukaryotic cytoskeleton is tightly regulated by a large number of actin‐ or microtubule‐associated proteins. In contrast, recently discovered bacterial actins and tubulins have few associated regulatory proteins. Hence, the quest to find basic principles that govern the formation of filamentous suprastructures is simplified in bacteria. Three common principles, which have been probed extensively during evolution, can be identified that lead to suprastructures formation: cationic counterion fluctuations; self‐association into liquid crystals; and molecular crowding. The underlying physics of these processes will be discussed with respect to physiological circumstance. © 2012 Wiley Periodicals, Inc
Towards a Sustainable Coffee Market: Paradoxes Faced by a Multinational Company
Authors: Kolk Ans 
Published: January 2012

ABSTRACTThis paper examines the case of sustainable coffee as faced by Sara Lee's International Coffee and Tea Division (SL), asking which strategic direction the company should take considering its regulatory, competitive, and societal contexts. More than a decade after sustainable coffee became a strategic issue for SL, emerging public purchasing guidelines seem to exclude the ‘mainstream‐market’ policy of the company and instead favour the Fairtrade standard that embodies a niche approach. The case presents the strategic, organisational, and marketing dimensions, in their international supply‐chain and industry dynamics. It raises the question what it means for a large, mainstream, multinational company to move to sustainability when the issues at hand are very complex, when consumer awareness is limited, and when the market for sustainable coffee is not yet mature. Several strategic options are presented, each with their pros and cons, as input for further discussion and research on the paradoxes related to sustainability and international business. Copyright © 2012 John Wiley & Sons, Ltd and ERP Environment.
Catalytic Hydrocarbon Functionalization with Gold Complexes Containing N‐Heterocyclic Carbene Ligands with Pendant Donor Groups
Authors: Delgado‐Rebollo Manuela , Beltrán Álvaro , Prieto Auxiliadora , Mar Díaz‐Requejo M. , Echavarren Antonio M. , Pérez Pedro J. 
Published: January 2012

AbstractA series of silver and gold complexes bearing N‐heterocyclic carbene ligands with a –CH2CO2Et pendant group attached to one N atom of the NHC ligand have been prepared. The catalytic properties of the gold complexes toward the decomposition of ethyl diazoacetate (N2CHCO2Et) and the transfer of the carbene CHCO2Et group to benzene and hexane have been investigated. A somewhat different reaction outcome has been found for this family of gold catalysts compared with the parent IPrAuCl catalyst.
Chiral separation of Huperzine A using CE – Method validation and application in pharmaceutical formulations
Authors: Tsioupi Despina A. , Nicolaou Irene N. , Moore Leonard , Kapnissi‐Christodoulou Constantina P. 
Published: January 2012

AbstractThe aim of this work is the development, validation and application of an MEKC method for the chiral separation of Huperzine A. Huperzine A is an important compound that is used to treat Alzheimer's disease. However, only the (−)‐form of this compound is biologically active and behaves as a potential acetylcholinesterase inhibitor. Therefore, the separation of the (−)‐form from the (+)‐form is of greatest importance. Optimal conditions, regarding resolution and analysis time, were established by altering several experimental parameters, such as temperature, field strength, pH, type and concentration of BGE and chiral selector. A major problem that had to be solved in this study was the low intensity and efficiency of the peaks. More parameters were examined, such as the addition of modifiers, to optimize further the separation, and particularly the efficiency. Baseline enantioseparation was achieved by using a BGE of 50 mM acetate (pH 5.0), supplemented with 0.2% w/v poly(sodium N‐undecanoyl‐ll‐alanyl‐valinate) and 10% v/v tert‐butanol. Finally, the optimum conditions were applied to a pharmaceutical formulation, to demonstrate the ability of the method to control the purity of the (−)‐Huperzine A in pharmaceutical formulations.
Flower and inflorescence development in Salicornia (Chenopodiaceae)
Authors: Beer Svetlana S. , Beer Anton S. , Sokoloff Dmitry D. 
Published: January 2012

AbstractFive species of Salicornia are investigated with respect to flower and inflorescence development. The triad of flowers likely represents a dichasium. Flowers possess three to four tepals, one or two stamens and two or three carpels. In the central flower of a triad, stamen insertion is always in the median plane, which is a major symmetry plane of a flower. Major symmetry planes of lateral flowers are usually parallel to the major symmetry plane of the central flower, whereas they are expected to be perpendicular to that of the central flower according to the dichasium model. This could be explained by strong displacement of positions of ablasted subtending bracts of lateral flowers from the transversal plane towards the subtending bract of the dichasium. This study showed the absence of a clear correlation between presence of one or two stamens and ploidy level in Salicornia. The species S. heterantha exhibits one of most curious combinations of different types of organ fusion in angiosperms. All three flowers of a dichasium have their perianth tube basally congenitally united with the main inflorescence axis. The distal part of the perianth tube of central flowers of S. heterantha is postgentinally fused to the inflorescence main axis. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Relationship of endothelial function and atherosclerosis to treatment response in late‐life depression
Authors: Paranthaman R. , Greenstein A. , Burns A. S. , Heagerty A. M. , Malik R. A. , Baldwin R. C. 
Published: January 2012

ObjectiveTreatment response in late‐life depression has been linked to cerebrovascular disease notably via the vascular depression hypothesis. This study investigated the relationship between endothelial function and atherosclerosis and treatment response to antidepressant monotherapy.MethodsTwenty five patients with late‐life depression were compared with 21 non‐depressed control subjects in a case control study. Nine of the depressed subjects were responders to antidepressant monotherapy and 16 were not. Vascular measures included assessment of carotid intima media thickness (IMT) representing atherosclerosis and biopsied small artery dilatation to acetylcholine to assess endothelial function in a subset of subjects.ResultsThere were no group differences in vascular risks or sociodemographic variables. There was a significant group difference (responders versus non‐responders versus controls) on both IMT and endothelial function (p < 0.01 and p < 0.05, respectively) with a significant difference between controls and non‐responders (p < 0.001) on IMT and between controls and responders (p < 0.05) and control versus non‐responders (p < 0.05) on endothelial function but no significant difference between responders and non‐responders. On both IMT and endothelial function, there was a gradient across groups, with control subjects having best vascular structure or function, non‐responders worse and responders in‐between.ConclusionsThe results are consistent with a hypothesis that poorer antidepressant response in later life depressive disorder may be linked to an underlying vascular dysfunction and pathology. The study is small, and the results require replication but if confirmed, trials with vasoprotective medication aimed at improving vascular function in order to alter the prognosis of late‐life depression would be a rational development. Copyright © 2012 John Wiley & Sons, Ltd.
Effectiveness of cevimeline to improve oral health in patients with postradiation xerostomia
Authors: Witsell David L. , Stinnett Sandra , Chambers Mark S. 
Published: January 2012

AbstractBackgroundWe assessed the effectiveness of cevimeline 30 mg 3 times daily in patient‐reported oral health (Oral Health Impact Profile [OHIP‐49]) and quality of life (QOL) in patients with xerostomia.MethodsIn our investigator‐initiated, multicenter, randomized, double‐blind, placebo‐controlled study, patients who received >40 Gy of radiation therapy to the head and neck including at least 3 major salivary glands were randomized to cevimeline 30 mg or placebo orally 3 times daily for 6 weeks. Patients had to have grade 1 or 2 xerostomia and be >16 weeks posttreatment. Clinical data were collected and questionnaires administered at baseline and week 6. The primary outcome was change in OHIP‐49 total score from baseline to week 6.ResultsNo statistically significant differences in oral health or QOL were observed. During the 6 weeks of the study, the severity of xerostomia decreased from baseline.ConclusionsXerostomia is a significant sequela of treatment of head and neck cancer that may improve with time. The role of oral parasympathetic muscarinic secretogogues in alleviating patient symptoms and complaints remains unclear. © 2012 Wiley Periodicals, Inc. Head Neck, 2012
Is antipsychotic treatment linked to low bone mineral density and osteoporosis? A review of the evidence and the clinical implications
Authors: Crews Matthieu P K , Howes Oliver D 
Published: January 2012

ObjectiveOsteoporosis is increasingly common worldwide and there is a growing concern that the long‐term use of antipsychotic medications increases the risk of this disorder. In this review, we consider whether antipsychotics may contribute to the development of osteoporosis through reductions in bone mineral density, discuss the possible mechanisms involved and consider the clinical implications of such a relationship.MethodsWe searched the literature for studies in this area published between 1966 and 2010 using the Medline and PubMed databases, supplemented by hand searches of retrieved reports.ResultsThe available data indicate that statistically significant reductions in bone mineral density are frequently seen in patients prescribed with antipsychotic medications and suggest that there is a higher incidence of clinically significant reductions compared with the normal population.ConclusionsClinicians should be aware for the potential negative effects of antipsychotic medications on bone mineral density, particularly in patients with additional risk factors for osteoporosis. Recommendations regarding routine monitoring of bone mineral density for patients prescribed antipsychotic medications cannot be made on the basis of existing evidence, and more research is required. Copyright © 2012 John Wiley & Sons, Ltd.