bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population‐based Tay‐Sachs screening among Ashkenazi Jewish young adults in the 21st century: Hexosaminidase a enzyme assay is essential for accurate testing
Authors: Schneider Adele , Nakagawa Sachiko , Keep Rosanne , Dorsainville Darnelle , Charrow Joel , Aleck Kirk , Hoffman Jodi , Minkoff Sherman , Finegold David , Sun Wei , Spencer Andrew , Lebow Johannah , Zhan Jie , Apfelroth Stephen , Schreiber‐Agus Nicole , Gross Susan 
Published: October 2009

AbstractTay‐Sachs disease (TSD) carrier screening, initiated in the 1970s, has reduced the birth‐rate of Ashkenazi Jews with TSD worldwide by 90%. Recently, several nationwide programs have been established that provide carrier screening for the updated panel of Jewish genetic diseases on college campuses and in Jewish community settings. The goals of this study were to determine the performance characteristics of clinical TSD testing in college‐ and community‐based screening programs and to determine if molecular testing alone is adequate in those settings. Clinical data for TSD testing were retrospectively anonymized and subsequently analyzed for 1,036 individuals who participated in these programs. The performance characteristics of the serum and the platelet Hexosaminidase assays were compared, and also correlated with the results of targeted DNA analysis. The serum assay identified 29 carriers and the platelet assay identified 35 carriers for carrier rates of 1/36 and 1/29, respectively. One hundred sixty‐nine samples (16.3%) were inconclusive by serum assay in marked contrast to four inconclusive samples (0.4%) by the platelet assay. Molecular analysis alone would have missed four of the 35 carriers detected by the platelet assay, yielding a false negative rate of 11.4% with a sensitivity of 88.6%. Based on the results of this study, platelet assay was superior to serum with a minimal inconclusive rate. Due to changing demographics of the Ashkenazi Jewish population, molecular testing alone in the setting of broad‐based population screening programs is not sufficient, and biochemical analysis should be the assay of choice. © 2009 Wiley‐Liss, Inc.
The genetics of sleep disorders in humans: Narcolepsy, restless legs syndrome, and obstructive sleep apnea syndrome
Authors: Caylak Emrah 
Published: October 2009

AbstractSleep disorders are a group of neurological disorders known to cause public health problems associated with interference with daily activities including cognitive problems, poor job performance and reduced productivity. There is strong evidence emerging for the presence of genes influencing sleep disorders, such as narcolepsy (NRCLP), restless legs syndrome (RLS), and obstructive sleep apnea syndrome (OSAS). NRCLP is typically characterized by excessive daytime sleepiness, cataplexy, sleep paralysis and hallucinations. RLS is manifested by compelling need to move the legs and usually experienced when trying to sleep. OSAS is major sleep problem characterized by recurrent episodes of upper airway collapse and obstruction during sleep. In the recent years, many research groups have attempted to identify the susceptibility and candidate genes for NRCLP, RLS, and OSAS through the sequential analyses of genetic linkage and association. The purpose of this review is to summarize some of remarkable molecular advances in sleep and sleep disorders, thereby providing a greater understanding of the complex sleep processes, and a platform for future therapeutic interventions. © 2009 Wiley‐Liss, Inc.
Diaryliodoniumsalze – aus dem Nichts ins Rampenlicht
Authors: Merritt Eleanor A. , Olofsson Berit 
Published: October 2009

AbstractDie jüngsten bahnbrechenden Entwicklungen bei der Anwendung von Diaryliodoniumsalzen in Kreuzkupplungsreaktionen haben diese ehemals unterentwickelte Klasse von Reagentien in die vorderste Reihe der organischen Chemie katapultiert. Mit dem Aufkommen neuartiger, einfacher, effizienter Methoden zur Synthese dieser Reagentien lassen sich noch sehr viel mehr Einsatzmöglichkeiten voraussehen. Wir bieten hier einen Überblick über die historischen und neuerlichen Fortschritte bei der Synthese und Anwendung von Diaryliodoniumsalzen.
New and Old Concepts in Thermoelectric Materials
Authors: Sootsman Joseph R. , Chung Duck Young , Kanatzidis Mercouri G. 
Published: October 2009

AbstractHerein we cover the key concepts in the field of thermoelectric materials research, present the current understanding, and show the latest developments. Current research is aimed at increasing the thermoelectric figure of merit (ZT) by maximizing the power factor and/or minimizing the thermal conductivity. Attempts at maximizing the power factor include the development of new materials, optimization of existing materials by doping, and the exploration of nanoscale materials. The minimization of the thermal conductivity can come through solid‐solution alloying, use of materials with intrinsically low thermal conductivity, and nanostructuring. Herein we describe the most promising bulk materials with emphasis on results from the last decade. Single‐phase bulk materials are discussed in terms of chemistry, crystal structure, physical properties, and optimization of thermoelectric performance. The new opportunities for enhanced performance bulk nanostructured composite materials are examined and a look into the not so distant future is attempted.
Magnetic survey in the investigation of sociopolitical change at a Late Bronze age fortress settlement in northwestern Armenia
Authors: Lindsay Ian , Smith Adam T. , Badalyan Ruben 
Published: October 2009

AbstractThe construction of large stone fortresses across much of northern Armenia during the Late Bronze Age (ca. 1500–1150 BC) represented a shift away from centuries of nomadic pastoralism, and also marked a profound transformation in the constitution of political authority and how social orders were mediated through the built environment. To date, however, little archaeological attention has been given to Late Bronze Age (LBA) settlements located outside the fortress citadels, partly due to the difficulty in detecting them from the surface. In this report we highlight results and observations from a magnetic gradiometry survey in northwestern Armenia where we test the hypothesis that an extensive LBA domestic complex existed at the base of the fortified hill at the site of Tsaghkahovit. The study surveyed four grids in the settlement area at the base of fortress. Three test units were excavated in three of the four survey areas to test selected anomalies. Two of the test units confirmed the presence of subsurface LBA deposits, including basalt stone walls, burned features, and a storage pit, appearing in the data as large dipoles. The spatial configurations of buildings revealed by the gradiometry surveys elucidate the extent of the Tsaghkahovit settlement and the formal differentiation of domestic and institutional spaces as new architectural traditions emerge during the Middle to Late Bronze Age transition. However, targeted subsurface tests also hint at the ephemeral nature of the domestic constructions suggesting the retention of mobility among subject populations under the authority of settled fortress elites. Copyright © 2009 John Wiley & Sons, Ltd.
Functional and work outcomes improve in patients with rheumatoid arthritis who receive targeted, comprehensive occupational therapy
Authors: Macedo Alyssa M. , Oakley Stephen P. , Panayi Gabriel S. , Kirkham Bruce W. 
Published: October 2009

AbstractObjectiveWork disability is a serious consequence of rheumatoid arthritis (RA). We conducted a 6‐month, prospective randomized controlled trial comparing assessments of function, work, coping, and disease activity in employed patients with RA receiving occupational therapy intervention versus usual care.MethodsEmployed patients with RA with increased perceived work disability risk were identified by the RA Work Instability Scale (WIS; score ≥10). Patients were stratified into medium‐ (score ≥10 and <17) and high‐risk (≥17) groups, then randomized into occupational therapy or usual care groups. Assessments were conducted at baseline and 6 months. The primary outcome was the Canadian Occupational Performance Measure (COPM), a standardized patient self‐report of function. Other outcomes included the disability index (DI) of the Health Assessment Questionnaire (HAQ); Disease Activity Score in 28 joints (DAS28); RA WIS; EuroQol Index; visual analog scales (VAS) for pain, work satisfaction, and work performance; and days missed/month. Independent sample t‐tests and Mann‐Whitney U tests were used.ResultsWe recruited 32 employed patients with RA. At baseline the groups were well matched. At 6 months the improvement in the occupational therapy group was significantly greater than that in the usual care group for all functional outcomes (COPM performance P < 0.001, COPM satisfaction P < 0.001, HAQ DI P = 0.02) and most work outcomes (RA WIS [P = 0.04], VAS work satisfaction [P < 0.001], VAS work performance [P = 0.01]). Additionally, Arthritis Helplessness Index (P = 0.02), Arthritis Impact Measurement Scales II pain subscale (P = 0.03), VAS pain (P = 0.007), EuroQol Index (P = 0.02), EuroQol global (P = 0.02), and DAS28 (P = 0.03) scores significantly improved.ConclusionTargeted, comprehensive occupational therapy intervention improves functional and work‐related outcomes in employed RA patients at risk of work disability.
The infrapatellar fat pad in knee osteoarthritis: An important source of interleukin‐6 and its soluble receptor
Authors: Distel Emilie , Cadoudal Thomas , Durant Sylvie , Poignard Alexandre , Chevalier Xavier , Benelli Chantal 
Published: October 2009

AbstractObjectiveObesity is a potent risk factor in knee osteoarthritis (OA). It has been suggested that adipokines, secreted by adipose tissue (AT) and largely found in the synovial fluid of OA patients, derive in part from the infrapatellar fat pad (IFP), also known as Hoffa's fat pad. The goal of this study was to characterize IFP tissue in obese OA patients and to compare its features with thigh subcutaneous AT to determine whether the IFP contributes to local inflammation in knee OA via production of specific cytokines.MethodsIFP and subcutaneous AT samples were obtained from 11 obese women (body mass index ≥30 kg/m2) with knee femorotibial OA. Gene expression was measured by real‐time quantitative polymerase chain reaction. Cytokine concentrations in plasma and in conditioned media of cultured AT explants were determined by enzyme‐linked immunosorbent assay or by Luminex xMAP technology.ResultsIn IFP tissue versus subcutaneous AT, there was a decrease in the expression of genes for key enzymes implicated in adipocyte lipid metabolism, whereas the expression levels of genes for AT markers remained similar. A 2‐fold increase in the expression of the gene for interleukin‐6 (IL‐6), a 2‐fold increase in the release of IL‐6, and a 3.6‐fold increase in the release of soluble IL‐6 receptor (sIL‐6R) were observed in IFP samples, compared with subcutaneous AT, but the rates of secretion of other cytokines in IFP samples were similar to the rates in subcutaneous AT. In addition, leptin secretion was decreased by 40%, whereas adiponectin secretion was increased by 70%, in IFP samples versus subcutaneous AT.ConclusionOur results indicate that the IFP cytokine profile typically found in OA patients could play a role in paracrine inflammation via the local production of IL‐6/sIL‐6R and that such a profile might contribute to damage in adjacent cartilage.
BANK1 is a genetic risk factor for diffuse cutaneous systemic sclerosis and has additive effects with IRF5 and STAT4
Authors: Dieudé P. , Wipff J. , Guedj M. , Ruiz B. , Melchers I. , Hachulla E. , Riemekasten G. , Diot E. , Hunzelmann N. , Sibilia J. , Tiev K. , Mouthon L. , Cracowski J. L. , Carpentier P. H. , Distler J. , Amoura Z. , Tarner I. , Avouac J. , Meyer O. , Kahan A. , Boileau C. , Allanore Y. 
Published: October 2009

AbstractObjectiveTo determine whether the functional BANK1 variants rs3733197 and rs10516487 are associated with systemic sclerosis (SSc) in 2 European Caucasian populations and to investigate the putative gene–gene interactions between BANK1 and IRF5 as well as STAT4.MethodsBANK1 single‐nucleotide polymorphisms were genotyped in a total population of 2,432 individuals. The French cohort consisted of 874 SSc patients and 955 controls (previously genotyped for both IRF5 rs2004640 and STAT4 rs7574865). The German cohort consisted of 421 SSc patients and 182 controls.ResultsThe BANK1 variants were found to be associated with diffuse cutaneous SSc (dcSSc) in both cohorts, providing an odds ratio (OR) of 0.77 for the rs10516487 T rare allele in the combined populations of dcSSc patients as compared with the combined populations of controls (95% confidence interval [95% CI] 0.64–0.93) and an OR of 0.73 (95% CI 0.61–0.87) for the rs3733197 A rare allele. BANK1 haplotype analysis found the A‐T haplotype to be protective in dcSSc patients (OR 0.70 [95% CI 0.57–0.86], P = 3.39 × 10−4) and the G‐C haplotype to be a risk factor (OR 1.25 [95% CI 1.06–1.47], P = 0.008). Significant differences were also observed when the limited cutaneous subset of SSc was compared with the dcSSc subset, both for the rare alleles and for the haplotypes. The BANK1, IRF5, and STAT4 risk alleles displayed a multiplicatively increased risk of dcSSc of 1.43‐fold.ConclusionOur results establish BANK1 as a new SSc genetic susceptibility factor and show that BANK1, IRF5, and STAT4 act with additive effects.
Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis
Authors: Appel Heiner , Ruiz‐Heiland Gisela , Listing Joachim , Zwerina Jochen , Herrmann Martin , Mueller Ruediger , Haibel Hildrun , Baraliakos Xenofon , Hempfing Axel , Rudwaleit Martin , Sieper Joachim , Schett Georg 
Published: October 2009

AbstractObjectiveOsteocytes are considered to be sensors of bone damage and regulators of bone mass by specifically expressing sclerostin, an inhibitor of bone formation. The contribution of osteocytes in regulating local bone remodeling in arthritis is unknown. The aim of this study was to investigate the role of osteocytes as contributors to bone remodeling in ankylosing spondylitis (AS).MethodsSclerostin expression and osteocyte death were assessed by immunohistochemistry in joints derived from patients with AS, patients with rheumatoid arthritis (RA), and patients with osteoarthritis (OA), as well as from control subjects. In addition, the serum level of sclerostin was assessed by enzyme‐linked immunosorbent assay in healthy subjects and patients with AS; this assessment included the longitudinal correlation of sclerostin serum levels and radiographic progression in the spine of patients with AS.ResultsSclerostin expression was confined exclusively to osteocytes. Whereas the majority of osteocytes in healthy individuals and patients with RA were sclerostin positive, expression was significantly reduced in patients with OA and was virtually absent in patients with AS. Moreover, serum levels of sclerostin were significantly lower in patients with AS than in healthy individuals. Importantly, low serum sclerostin levels in patients with AS were significantly associated with the formation of new syndesmophytes (P = 0.007).ConclusionSclerostin expression is impaired in patients with AS, suggesting a specific alteration of osteocyte function in this disease. A low serum level of sclerostin in the setting of AS is linked to increased structural damage, emphasizing the role of sclerostin in the suppression of bone formation.
The relationship between synovial lymphocyte aggregates and the clinical response to infliximab in rheumatoid arthritis: A prospective study
Authors: Klaasen Ruth , Thurlings Rogier M. , Wijbrandts Carla A. , van Kuijk Arno W. , Baeten Dominique , Gerlag Danielle M. , Tak Paul P. 
Published: October 2009

AbstractObjectiveSome patients with rheumatoid arthritis (RA) exhibit lymphocyte aggregates in the synovium. This study was undertaken to address whether the presence of lymphocyte aggregates before treatment could serve as a biomarker for the clinical response to tumor necrosis factor (TNF) blockade, and to confirm whether the aggregation of synovial lymphocytes is reversible after anti‐TNF treatment.MethodsSynovial tissue biopsy samples were obtained from 97 patients with active RA before the initiation of infliximab treatment. Lymphocyte aggregates in the synovial tissue were counted and also graded for size. Logistic regression analysis was performed to identify whether the presence of lymphocyte aggregates could be a predictor of the clinical response at week 16. Furthermore, the effects of TNF blockade on lymphocyte aggregates were compared between patients with RA and patients with psoriatic arthritis (PsA).ResultsFifty‐seven percent of RA synovial tissue samples contained lymphocyte aggregates, and 32% of the patients had large aggregates. Aggregates were found in 67% of clinical responders compared with 38% of nonresponders. The presence of aggregates at baseline was a highly significant predictor of the clinical response to anti‐TNF treatment (R2 = 0.10, P = 0.008). Positivity for lymphocyte aggregates increased the power to predict the clinical response (R2 = 0.29), when analyzed in a prediction model that included baseline disease activity evaluated by the Disease Activity Score in 28 joints, anti–cyclic citrullinated peptide antibody positivity, and synovial TNFα expression. There was a reduction in lymphocyte aggregates after anti‐TNF antibody therapy in both RA and PsA.ConclusionRA patients with synovial lymphocyte aggregates have, on average, a better response to infliximab treatment than those with only diffuse leukocyte infiltration. Moreover, the aggregation of synovial lymphocytes is reversible after anti‐TNF antibody treatment.
Tumor necrosis factor α and interleukin‐1β modulate calcium and nitric oxide signaling in mechanically stimulated osteocytes
Authors: Bakker A. D. , da Silva V. C. , Krishnan R. , Bacabac R. G. , Blaauboer M. E. , Lin Y.‐C. , Marcantonio R. A. C. , Cirelli J. A. , Klein‐Nulend J. 
Published: October 2009

AbstractObjectiveInflammatory diseases often coincide with reduced bone mass. Mechanoresponsive osteocytes regulate bone mass by maintaining the balance between bone formation and resorption. Despite its biologic significance, the effect of inflammation on osteocyte mechanoresponsiveness is not understood. To fill this gap, we investigated whether the inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β) modulate the osteocyte response to mechanical loading.MethodsMLO‐Y4 osteocytes were incubated with TNFα (0.5–30 ng/ml) or IL‐1β (0.1–10 ng/ml) for 30 minutes or 24 hours, or with calcium inhibitors for 30 minutes. Cells were subjected to mechanical loading by pulsatile fluid flow (mean ± amplitude 0.7 ± 0.3 Pa, 5 Hz), and the response was quantified by measuring nitric oxide (NO) production using Griess reagent and by measuring intracellular calcium concentration ([Ca2+]i) using Fluo‐4/AM. Focal adhesions and filamentous actin (F‐actin) were visualized by immunostaining, and apoptosis was quantified by measuring caspase 3/7 activity. Cell‐generated tractions were quantified using traction force microscopy, and cytoskeletal stiffness was quantified using optical magnetic twisting cytometry.ResultsPulsatile fluid flow increased [Ca2+]iwithin seconds (in 13% of cells) and NO production within 5 minutes (4.7‐fold). TNFα and IL‐1β inhibited these responses. Calcium inhibitors decreased pulsatile fluid flow–induced NO production. TNFα and IL‐1β affected cytoskeletal stiffness, likely because 24 hours of incubation with TNFα and IL‐1β decreased the amount of F‐actin. Incubation with IL‐1β for 24 hours stimulated osteocyte apoptosis.ConclusionOur results suggest that TNFα and IL‐1β inhibit mechanical loading–induced NO production by osteocytes via abrogation of pulsatile fluid flow–stimulated [Ca2+]i, and that IL‐1β stimulates osteocyte apoptosis. Since both NO and osteocyte apoptosis affect osteoclasts, these findings provide a mechanism by which inflammatory cytokines might contribute to bone loss and consequently affect bone mass in rheumatoid arthritis.
Brain involvement in rheumatoid arthritis: A magnetic resonance spectroscopy study
Authors: Emmer Bart J. , van der Bijl A. Egon , Huizinga Tom W. J. , Breedveld Ferdinand C. , Steens Stefan C. A. , Th. Bosma Gerlof P. , van Buchem Mark A. , van der Grond Jeroen 
Published: October 2009

AbstractObjectiveTumor necrosis factor α was recently implicated as an important mediator of communication between the peripheral and cerebral immune systems in an animal model of chronic inflammation. The purpose of this study was to examine by proton magnetic resonance spectroscopy (1H‐MRS) the influence of inflammation on cerebral metabolism in patients with rheumatoid arthritis (RA).MethodsSingle‐voxel 1H‐MRS of the centrum semiovale was performed on 35 RA patients (6 men and 29 women; mean ± SD age 51.8 ± 14.6 years) and 28 healthy age‐ and sex‐matched control subjects (9 men and 19 women; mean ± SD age 50.2 ± 10.4 years). None of the study subjects had any neurologic signs or symptoms. Clinical markers of disease activity were correlated with the 1H‐MRS findings.ResultsPatients with active RA, as reflected by an elevated erythrocyte sedimentation rate (ESR), had a significantly higher ratio of choline to creatine and a significantly lower ratio of N‐acetylaspartate to choline than did patients with inactive RA, as reflected by a normal ESR. Moreover, the ratios of choline to creatine and NAA to choline were significantly correlated with the ESR after correction for age, sex, smoking status, handedness, alcohol consumption, medication use, and disease duration. Medication use had no additional effect on these associations.ConclusionOur data show that systemic inflammation in RA is associated with metabolic changes in the brain.