bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene Expression Factor Analysis to Differentiate Pathways Linked to Fibromyalgia, Chronic Fatigue Syndrome, and Depression in a Diverse Patient Sample
Authors: Iacob Eli , Light Alan R. , Donaldson Gary W. , Okifuji Akiko , Hughen Ronald W. , White Andrea T. , Light Kathleen C. 
Published: June 2015

ObjectiveTo determine if independent candidate genes can be grouped into meaningful biologic factors, and whether these factors are associated with the diagnosis of chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS), while controlling for comorbid depression, sex, and age.MethodsWe included leukocyte messenger RNA gene expression from a total of 261 individuals, including healthy controls (n = 61), patients with FMS only (n = 15), with CFS only (n = 33), with comorbid CFS and FMS (n = 79), and with medication‐resistant (n = 42) or medication‐responsive (n = 31) depression. We used exploratory factor analysis (EFA) on 34 candidate genes to determine factor scores and regression analysis to examine whether these factors were associated with specific diagnoses.ResultsEFA resulted in 4 independent factors with minimal overlap of genes between factors, explaining 51% of the variance. We labeled these factors by function as 1) purinergic and cellular modulators, 2) neuronal growth and immune function, 3) nociception and stress mediators, and 4) energy and mitochondrial function. Regression analysis predicting these biologic factors using FMS, CFS, depression severity, age, and sex revealed that greater expression in factors 1 and 3 was positively associated with CFS and negatively associated with depression severity (Quick Inventory for Depression Symptomatology score), but not associated with FMS.ConclusionExpression of candidate genes can be grouped into meaningful clusters, and CFS and depression are associated with the same 2 clusters, but in opposite directions, when controlling for comorbid FMS. Given high comorbid disease and interrelationships between biomarkers, EFA may help determine patient subgroups in this population based on gene expression.
Physician Preferences and Variations in Prescription of Biologic Drugs for Rheumatoid Arthritis: A Register‐Based Study of 4,010 Patients in Sweden
Authors: Kalkan Almina , Husberg Magnus , Hallert Eva , Roback Kerstin , Thyberg Ingrid , Skogh Thomas , Carlsson Per 
Published: June 2015

ObjectiveThe prescription of biologic drugs for rheumatoid arthritis (RA) patients has varied considerably across different regions. Previous studies have shown physician preferences to be an important determinant in the decision to select biologic disease‐modifying antirheumatic drugs (bDMARDs) rather than nonbiologic, synthetic DMARDs (sDMARDs) alone. The aim of this study was to test the hypothesis that physician preferences are an important determinant for prescribing bDMARDs for RA patients in Sweden.MethodsUsing data from the Swedish Rheumatology Quality Register, we identified 4,010 RA patients who were not prescribed bDMARDs during the period 2008–2012, but who, on at least 1 occasion, had an sDMARD prescription and changed treatment for the first time to either a new sDMARD or a bDMARD. Physician preference for the use of bDMARDs was calculated using data on each physician's prescriptions during the study period. The relationship between prescription of a bDMARD and physician preference, controlling for patient characteristics, disease activity, and the physician's local context was evaluated using multivariate logistic regression.ResultsWhen adjusting for patient characteristics, disease activity, and the physician's local context, physician preference was an important predictor for prescription of bDMARDs. Compared with patients of a physician in the lowest preference tertile, patients of physicians in the highest and middle tertiles had an odds ratio for receiving bDMARDs of 2.8 (95% confidence interval [95% CI] 2.13–3.68) and 1.28 (95% CI 1.05–1.57), respectively.ConclusionPhysician preference is an important determinant for prescribing bDMARDs.
Annual Incidence of Knee Symptoms and Four Knee Osteoarthritis Outcomes in the Johnston County Osteoarthritis Project
Authors: Murphy Louise B. , Moss Susan , Do Barbara T. , Helmick Charles G. , Schwartz Todd A. , Barbour Kamil E. , Renner Jordan , Kalsbeek William , Jordan Joanne M. 
Published: June 2015

ObjectiveTo estimate annual incidence rates (IRs) of knee symptoms and 4 knee osteoarthritis (OA) outcomes (radiographic, symptomatic, severe radiographic, and severe symptomatic), overall and stratified by sociodemographic characteristics and knee OA risk factors.MethodsWe analyzed baseline (1991–1997) and first followup (1999–2003) data (n = 1,518) from the Johnston County Osteoarthritis Project. Participants were African American and white adults, ages ≥45 years, living in Johnston County, North Carolina, US. Knee symptoms were pain, aching, or stiffness on most days in a knee. Radiographic OA was Kellgren/Lawrence grade ≤2 (severe radiographic ≥3) in at least 1 knee. Symptomatic OA was defined as symptoms in a radiographically affected knee; severe symptomatic OA was defined as severe symptoms and severe radiographic OA.ResultsThe median followup time was 5.5 years. Average annual IRs were 6% for symptoms, 3% for radiographic OA, 2% for symptomatic OA, 2% for severe radiographic OA, and 0.8% for severe symptomatic OA. Across outcomes, IRs were highest among those with the following baseline characteristics: age ≥75 years, obese, a history of knee injury, or an annual household income ≤$15,000.ConclusionThe annual onset of knee symptoms and 4 OA outcomes in Johnston County was high. This may preview the future of knee OA in the US and underscores the urgency of clinical and public health collaborations that reduce risk factors for, and manage the impact of, these outcomes. Inexpensive, convenient, and proven strategies (e.g., physical activity, self‐management education courses) complement clinical care and can reduce pain and improve quality of life for people with arthritis.
Cause‐Specific Mortality in Male US Veterans With Rheumatoid Arthritis
Authors: England Bryant R. , Sayles Harlan , Michaud Kaleb , Caplan Liron , Davis Lisa A. , Cannon Grant W. , Sauer Brian C. , Solow Elizabeth B. , Reimold Andreas M. , Kerr Gail S. , Schwab Pascale , Baker Josh F. , Mikuls Ted R. 
Published: June 2015

ObjectiveThere has been limited investigation into cause‐specific mortality and the associated risk factors in men with rheumatoid arthritis (RA). We investigated all‐cause and cause‐specific mortality in men with RA, examining determinants of survival.MethodsMen from a longitudinal RA registry were followed from enrollment until death or through 2013. Vital status and cause of death were determined using the National Death Index. Crude mortality rates and standardized mortality ratios (SMRs) were calculated for all‐cause, cardiovascular disease (CVD), cancer, and respiratory mortality. Associations with all‐cause and cause‐specific mortality were examined using multivariable Cox proportional hazards and competing‐risks regression.ResultsThere were 1,652 men with RA and 332 deaths. The leading causes of death were CVD (31.6%; SMR 1.77 [95% confidence interval (95% CI) 1.46–2.14]), cancer (22.9%; SMR 1.50 [95% CI 1.20–1.89]), and respiratory disease (15.1%; SMR 2.90 [95% CI 2.20–3.83]). Factors associated with all‐cause mortality included older age, white race, smoking, low body weight, comorbidity, disease activity, and prednisone use. Rheumatoid factor concentration and nodules were associated with CVD mortality. There were no associations of methotrexate or biologic agent use with all‐cause or cause‐specific mortality.ConclusionMen in this RA cohort experienced increased all‐cause and cause‐specific mortality, with a 3‐fold risk of respiratory‐related deaths compared to age‐matched men in the general population. Further studies are needed in order to examine whether interventions targeting potentially modifiable correlates of mortality might lead to improved long‐term survival in men with RA.
Comparison of Care Provided in Practices With Nurse Practitioners and Physician Assistants Versus Subspecialist Physicians Only: A Cohort Study of Rheumatoid Arthritis
Authors: Solomon Daniel H. , Fraenkel Liana , Lu Bing , Brown Erika , Tsao Peter , Losina Elena , Katz Jeffrey N. , Bitton Asaf 
Published: June 2015

ObjectiveThe Affordable Care Act proposes wider use of nurse practitioners (NPs) and physician assistants (PAs), but little is known about outcomes of care provided by them in medical specialties. We compared the outcomes of care for patients with rheumatoid arthritis (RA) seen in practices with NPs or PAs and rheumatologists versus practices with rheumatologists only.MethodsWe enrolled 7 rheumatology practices in the US (4 with NPs or PAs and 3 without). RA disease activity (categorized as in remission, low, moderate, or high, using standardized measures) was abstracted from medical records from the most recent 2 years. We performed a repeated‐measures analysis using generalized linear regression to compare disease activity for visits to practices with NPs or PAs versus rheumatologist‐only practices, adjusting for disease duration, serologic status, RA treatments, and disease activity measures.ResultsRecords from 301 patients, representing 1,982 visits, were reviewed. The patients’ mean age was 61 years and 77% were female. In the primary adjusted analysis, patients seen in practices with NPs or PAs were less likely to have higher disease activity (odds ratio 0.32, 95% confidence interval 0.17–0.60; P = 0.004) than those seen in rheumatologist‐only practices. However, there were no differences in the change in disease activity.ConclusionPatients seen in practices with NPs or PAs had lower RA disease activity over 2 years compared to those seen in rheumatologist‐only practices; no differences were observed in the change in disease activity between visits either within or between the different types of provider practice.
Mini‐Residency in Musculoskeletal Care: An Interprofessional, Mixed‐Methods Educational Initiative for Primary Care Providers
Authors: Battistone Michael J. , Barker Andrea M. , Lawrence Phillip , Grotzke Marissa P. , Cannon Grant W. 
Published: June 2015

ObjectiveA structured educational effort to train primary care providers (PCPs) to perform joint injections has been projected to be cost effective. The US Department of Veterans Affairs (VA) is developing a national continuing professional development program to train PCPs in the evaluation and management of patients with common musculoskeletal conditions. The objective of this pilot project was to confirm initial projections of cost effectiveness and to inform further efforts to develop this program on a national scale.MethodsThe Salt Lake City VA served as the national hub for this pilot project. The initial phase included 19 providers, who participated in a weeklong mixed‐methods course. Evaluation was conducted by the VA Employee Education System. Assessments included anonymous surveys, structured telephone interviews, and a review of de‐identified procedure codes.ResultsThe survey response rate was 100%, with uniformly positive results. All participants recommended the expansion of this program. The mean number of joint injections performed each month increased from 0.3 (precourse) to 3.5 (postcourse), congruent with prior analyses projecting program cost effectiveness.ConclusionThe musculoskeletal mini‐residency is a well‐received program, with early evidence of cost effectiveness and impact aligned with course objectives. This pilot program is a foundation for efforts in the national dissemination of this initiative.
Epidemiology and Treatment of New‐Onset and Established Rheumatoid Arthritis in an Insured US Population
Authors: Crane Martin M. , Juneja Maneesh , Allen Jeffery , Kurrasch Regina H. , Chu Myron E. , Quattrocchi Emilia , Manson Stephanie C. , Chang David J. 
Published: June 2015

ObjectiveTo investigate the epidemiology and treatment of rheumatoid arthritis (RA) in a population broadly representative of employed adults in the US, using a retrospective cohort design.MethodsIncident and prevalent RA cohorts were defined from a sample of 4.66 million adults with complete followup data from the period of January 2005 through September 2008 in the Pharmetrics medical claims database. Demographics, comorbidity, and medical therapies were summarized using descriptive statistics.ResultsMedian duration in the database was 5.7 years. Age‐ and sex‐adjusted incidence in 2006 was 0.71 per 1,000 persons at risk (n = 3,992) and prevalence in 2005 was 0.63% (n = 30,530). Within 12 months after diagnosis, 65%, 64%, and 20% of the incident cohort had been prescribed corticosteroids, nonbiologic disease‐modifying antirheumatic drugs (DMARDs), and tumor necrosis factor (TNF) inhibitors, respectively. Median time to first anti‐TNF prescription was 6 months; 31% switched to a second drug and 15% to a third. An aggressive subcohort (11% of incident patients) received more DMARDs (83%) and TNF inhibitors (43%), and was more likely to switch. Twenty‐eight percent of incident patients received only symptomatic therapy over a minimum of 1.75 years of followup; these patients were older with more comorbidities and contraindications to methotrexate.ConclusionIn this insured population‐based cohort, only two‐thirds of newly diagnosed RA patients were prescribed a DMARD in year 1 and 28% received no antirheumatic therapy. Although limited by lack of clinical information and by left‐censoring, administrative databases capture clinical practice and suggest that gaps exist in treatment options available to a significant number of patients.
Aging Processes in Ultrafine‐Grained Low‐Alloyed Bronzes Subjected to Equal Channel Angular Pressing
Authors: Dobatkin Sergey V. , Bochvar Natalia R. , Shangina Daria V. 
Published: June 2015

AbstractThe aging processes in Cu‐0.7% Cr, Cu‐0.9% Hf, and Cu‐0.7% Cr‐0.9% Hf alloys after equal channel angular pressing have been studied. ECAP leads to strong grain refinement (200 nm for Cu‐0.7% Cr‐0.9% Hf alloy). It was shown that the Cu5Hf particles are more efficient as strengthening phase than the particles of Cr‐based solid solution. Alloying with hafnium also improves the thermal stability of hardening and minimizes recrystallization processes at aging temperatures. Temperature‐time aging regimes of bronzes for achieving optimal combination of strength, ductility, and electrical conductivity were also determined. Ternary alloy after aging at 500 °C for 2.5 h has a tensile strength of 582 MPa, an elongation of 18%, and an electrical conductivity of 75% IACS.
Enhanced Photocurrent Generation in Graphene/Copper Phthalocyanine/Mg–Al‐Layered Double Hydroxide Layer‐by‐Layer Multilayers
Authors: Yang Qinzheng , Yang Jing , Jiang Fujiao , Zhao Huazhang 
Published: June 2015

AbstractIn the paper, we demonstrated the controlled fabrication of nanostructured graphene/copper phthalocyanine/layered double hydroxide (G/TSCuPc/LDH) films by layer‐by‐layer assembly. The G/TSCuPc/LDH‐modified electrodes exhibited remarkable photoelectric performance, and its light absorption and resistance were increased with the increase of the film thickness. The electroactivity of the film was enhanced by the incorporation of graphene into TSCuPc. The 20‐layer film electrode generated higher photocurrent than the G/TSCuPc electrode, suggesting orderly assembled phthalocyanine layer between LDH and graphene layers and the efficient charge separation and electron transfer in the novel system.
Epimerization of the α Stereocenter in d‐Ribose‐Derived Nitrones: Direct Access to Variant Quinolizidines with d‐Ribo and d‐Arabino Configurations
Authors: Rowicki Tomasz , Malinowski Maciej , Łapczyński Sebastian , Gryszel Maciej , Czerwińska Karolina , Madura Izabela , Sas Wojciech 
Published: June 2015

AbstractThe concise synthesis of two polyhydroxyquinolizidines from 2,3‐O‐isopropylidene‐d‐ribofuranose was accomplished. Epimerization of the intermediate N‐(3‐alkenyl)nitrone resulted in exceptionally straightforward access to an iminosugar with a d‐arabino configuration. A plausible mechanism of the epimerization via nitrone‐enehydroxylamine tautomerism explaining the reaction course has been proposed.
Synthesis and the Stimuli‐Responsive Characteristics of Cyclic Cholamide Nicotinamide Adenine Dinucleotide (NAD+) Derivative with Aggregation in Basic Aqueous Solution
Authors: Li Dazhi , Yang Yunxu , Hu Biwei , Yang Chao , Huo Baolong , Wang Aizhi , Yu Feifei , Xue Lingwei , Dong Yajun , Fan Weiping 
Published: June 2015

AbstractA cyclic cholamide nicotinamide adenine dinucleotide (NAD+) derivative (CCN) has been synthesized with high yield. CCN is able to form nanomicelles in basic aqueous solution and emits fluorescence. The emission intensity shows a good linear relation and a good reversibility with pH value (pH 7–11). The mechanism for pH‐mediated changes in optical properties was demonstrated to be the tautomeric equilibriums of CCN/CCN‐OH.
Iodine‐Catalyzed Facile Synthesis of Pyrrolo‐ and Indolo[1,2‐a]quinoxalines
Authors: Wang Chao , Li Yun , Guo Rui , Tian Jingjing , Tao Cheng , Cheng Bin , Wang Hongyu , Zhang Jun , Zhai Hongbin 
Published: June 2015

AbstractA practical and green approach to pyrrolo‐ and indolo[1,2‐a]quinoxalines has been developed based upon an oxidative reaction of 1‐(2‐aminophenyl)pyrroles or 2‐(3‐methyl‐1H‐1‐indolyl)aniline with benzylamines in the presence of O2 as the environmentally friendly oxidant and iodine as an economical and effective catalyst.
Cumyl Hydroperoxide‐Promoted Oxidative Amidation of 2‐Oxoaldehydes with Amines under Metal‐Free Conditions for the Synthesis of Unsymmetrical Oxamides
Authors: Zheng Yang , Zhan Zhen , Cheng Xu , Ma Xiaojun , Li Jie , Hai Li , Wu Yong 
Published: June 2015

AbstractAn efficient cumyl hydroperoxide‐promoted oxidative coupling of 2‐oxoaldehydes and amines to give unsymmetrical oxamides has been developed. The reactions proceeded smoothly at room temperature under metal‐free conditions and generated the corresponding products in good yields. The mild method can tolerate a variety of functional groups, and is operationally simple.
Theoretical Studies on the Mechanism of the Michael Addition Reaction Catalyzed by a Thiourea‐Cinchona‐Amine: Triple Activation
Authors: Zhou Mei‐Juan , Li Yun , Dang Li 
Published: June 2015

AbstractThis paper attempts to illuminate the mechanism of the catalytic Michael addition of 2,4‐pentanedione with acrylaldehyde mediated by a thiourea‐cinchona‐amine catalyst via density functional theory calculations. The calculated results show that the C−C coupling easily occurs once the electronegative and electropositive sites of the reactants are generated by the catalyst. However, the previously proposed mechanism with the formation of an imine from the carbonyl group of reactants and the amine group of catalyst fails due to high reaction barriers for both the formation of the imine and the hydrolysis of the imine with water in order to regenerate the catalyst. Instead, the reaction pathways going through the protonation of the amine in the catalyst and formation of hydrogen bonds between the reactants and catalyst have smaller barriers. Our study will be helpful in designing new catalysts or extending the substrate scope of the reaction.
Modulation of Creutzfeldt‐Jakob disease prion propagation by the A224V mutation
Authors: Watts Joel C. , Giles Kurt , Serban Ana , Patel Smita , Oehler Abby , Bhardwaj Sumita , Guan Shenheng , Greicius Michael D. , Miller Bruce L. , DeArmond Stephen J. , Geschwind Michael D. , Prusiner Stanley B. 
Published: June 2015

ObjectiveMutations in the gene encoding the prion protein (PrP) are responsible for approximately 10 to 15% of cases of prion disease in humans, including Creutzfeldt‐Jakob disease (CJD). Here, we report on the discovery of a previously unreported C‐terminal PrP mutation (A224V) in a CJD patient exhibiting a disease similar to the rare VV1 subtype of sporadic (s) CJD and investigate the role of this mutation in prion replication and transmission.MethodsWe generated transgenic (Tg) mice expressing human PrP with the V129 polymorphism and A224V mutation, denoted Tg(HuPrP,V129,A224V) mice, and inoculated them with different subtypes of sCJD prions.ResultsTransmission of sCJD VV2 or MV2 prions was accelerated in Tg(HuPrP,V129,A224V) mice, compared to Tg(HuPrP,V129) mice, with incubation periods of ∼110 and ∼210 days, respectively. In contrast, sCJD MM1 prions resulted in longer incubation periods in Tg(HuPrP,V129,A224V) mice, compared to Tg(HuPrP,V129) mice (∼320 vs. ∼210 days). Prion strain fidelity was maintained in Tg(HuPrP,V129,A224V) mice inoculated with sCJD VV2 or MM1 prions, despite the altered replication kinetics.InterpretationOur results suggest that A224V is a risk factor for prion disease and modulates the transmission behavior of CJD prions in a strain‐specific manner, arguing that residues near the C‐terminus of PrP are important for controlling the kinetics of prion replication. Ann Neurol 2015;78:540–553
The Higgs boson, supersymmetry and dark matter: Relations and Perspectives
Authors: Arbey Alexandre , Battaglia Marco , Mahmoudi Farvah 
Published: June 2015

The discovery of a light Higgs boson at the LHC opens a broad program of studies and measurements to understand the role of this particle in connection with New Physics and Cosmology. Supersymmetry is the best motivated and most thoroughly formulated and investigated model of New Physics which predicts a light Higgs boson and can explain dark matter. This paper discusses how the study of the Higgs boson connects with the search for supersymmetry and for dark matter at the LHC and at a future collider and with dedicated underground dark matter experiments.
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Faltungszustand des Proteins Tau bei Bindung an Mikrotubuli
Authors: Kadavath Harindranath , Jaremko Mariusz , Jaremko Łukasz , Biernat Jacek , Mandelkow Eckhard , Zweckstetter Markus 
Published: June 2015

AbstractMikrotubuli werden durch so genannte Mikrotubuli‐assoziierte Proteine reguliert. Wenig ist jedoch über die Struktur dieser Proteine im Komplex mit Mikrotubuli bekannt. Hier zeigen wir, dass das Mikrotubuli‐assoziierte Protein Tau, das in Lösung intrinsisch ungeordnet ist, bei Bindung an Mikrotubuli lokal in eine stabile Struktur faltet. Während Tau flexibel in Lösung ist und eine β‐Faltblattstruktur in Amyloidfibrillen annimmt, falten die konservierten Hexapeptide in den Wiederholungssequenzen 2 und 3 in eine Haarnadelschleife im Komplex mit Mikrotubuli. Dies zeigt, dass die Bindung an Mikrotubuli eine spezifische Konformation im Tau‐Protein stabilisiert.
Die radiative Lebensdauer von Ytterbium‐Cryptaten mit Nahinfrarot‐Lumineszenz – Der Schlüssel zu extrem hohen Quantenausbeuten
Authors: Doffek Christine , Seitz Michael 
Published: June 2015

AbstractEine effektive Strategie zur Verbesserung der Lanthanoidenlumineszenz im Nahinfrarot‐Bereich wurde erstmals erfolgreich eingesetzt. Diese involviert die systematische Verkürzung der radiativen Lumineszenzlebensdauer τrad in molekularen Ytterbium‐Komplexen. Der zweizähnige Chelatligand 2,2′‐Bipyridin‐N,N′‐dioxid wurde als entscheidendes Strukturelement für die signifikante Senkung von τrad in makrobicyclischen Yb‐Cryptaten identifiziert. Wird dieser neue Ansatz mit herkömmlichen Strategien kombiniert, so können bisher unerreichte absolute Quantenausbeuten von bis zu 12 % erzielt werden. Diese außergewöhnliche Effizienz stellt den höchsten Wert dar, der jemals für jegliche Art von molekularen Lanthanoidspezies im nahen Infrarot‐Bereich gemessen wurde. Der hier erbrachte Beweis der prinzipiellen Durchführbarkeit dieser Strategie eröffnet neue Perspektiven für das Gebiet der Lanthanoiden‐Lumineszenz.