bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal flood sensitivity to annual precipitation: Evidence for landscape‐climate coevolution
Authors: Perdigão Rui A. P. , Blöschl Günter 
Published: June 2014

AbstractThis study investigates the sensitivity of floods to annual precipitation in space and time and evaluates quantitative signs of landscape‐climate coevolution. For that purpose, a spatiotemporal sensitivity analysis is performed at regional scale using data from 804 catchments in Austria from 1976 to 2008. Results show that flood peaks are more responsive to spatial (regional) than to temporal (decadal) variability. Space‐wise a 10% increase in precipitation leads to a 23% increase in flood peaks in Austria, whereas time‐wise a 10% increase in precipitation leads to an increase of just 6% in flood peaks. Catchments from dry lowlands and high wetlands exhibit similarity between the spatial and temporal sensitivities (spatiotemporal symmetry) and low landscape‐climate codependence. This suggests that such regions are not coevolving significantly. However, intermediate regions show differences between those sensitivities (symmetry breaks) and higher landscape‐climate codependence, suggesting undergoing coevolution. A new coevolution index is then proposed relating spatiotemporal symmetry with relative characteristic celerities. The descriptive assessment of coevolution is complemented by a simple dynamical model of landscape‐climate coevolution, in which landform evolution processes take place at the millennial scale (slow dynamics), and climate adjusts in years to decades (fast dynamics). Coevolution is expressed by the interplay between slow and fast dynamics, represented, respectively, by spatial and temporal characteristics. The model captures key features of the joint landscape‐climate distribution, supporting the descriptive assessment. This paper ultimately brings to light that coevolution needs to be taken into account through characteristic celerities in space‐time trading of regional hydrology.
Use of Oral and Subcutaneous Methotrexate in Rheumatoid Arthritis Patients in the United States
Authors: Curtis Jeffrey R. , Zhang Jie , Xie Fenglong , Beukelman Tim , Chen Lang , Fernandes Joaquim , Ginsberg Seth , Spettell Claire , Yun Huifeng , Saag Kenneth G. , Schiff Michael 
Published: June 2014

ObjectiveTo examine the patterns of methotrexate (MTX) use among rheumatoid arthritis (RA) patients.MethodsUsing data from RA patients enrolled in a US commercial health plan and the US Medicare program, we identified RA patients initiating oral MTX. Persistence with MTX (oral or subcutaneous [SC]) was defined as no gap for ≥90 days.ResultsNew oral MTX users in Medicare (n = 20,431) were 76.9% women, had a mean ± SD age of 69.7 ± 11.7 years, and contributed a median followup of 2.6 years (interquartile range 1.7–3.5 years). Only 38% received dosages ≥20 mg/week at any time. Approximately 50% of patients discontinued MTX at 1 year, although more than one‐third of patients subsequently restarted. New commercially insured oral MTX users (n = 4,048) were similar to Medicare patients, except for age. Among Medicare patients, 19% starting oral MTX subsequently initiated a biologic agent, mostly anti–tumor necrosis factor (85%). Of these, only 50% received MTX at a dosage of ≥20 mg/week, and only 21% of individuals switched to SC MTX (4%) or received hydroxychloroquine (8%), sulfasalazine (5%), or leflunomide (8%) prior to biologic agents. In commercially insured patients, 35% initiated a biologic agent, mostly anti–tumor necrosis factor therapies (90%). Of these, 43% never received MTX ≥20 mg/week.ConclusionTitration to a higher‐dose oral MTX and use of SC MTX among RA patients were infrequent and may have been underutilized. Further work to optimize MTX dosing before patients are switched to a biologic agent may be warranted.
Subcutaneous Tocilizumab Versus Placebo in Combination With Disease‐Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis
Authors: Kivitz Alan , Olech Ewa , Borofsky Michael , Zazueta Beatriz M. , Navarro‐Sarabia Federico , Radominski Sebastião C. , Merrill Joan T. , Rowell Lucy , Nasmyth‐Miller Clare , Bao Min , Wright Stephen , Pope Janet E. 
Published: June 2014

ObjectiveThe efficacy and safety of subcutaneous tocilizumab (TCZ‐SC) versus subcutaneous placebo (PBO‐SC) was evaluated in patients with rheumatoid arthritis who had an inadequate response to disease‐modifying antirheumatic drugs in the BREVACTA study.MethodsPatients (n = 656) were randomized 2:1 to receive TCZ‐SC 162 mg every other week or PBO‐SC every other week for 24 weeks; 20% previously received anti–tumor necrosis factor treatment. Escape therapy with TCZ‐SC 162 mg weekly was offered from week 12 for inadequate response. The primary end point was the American College of Rheumatology 20% improvement (ACR20) response at week 24. The key secondary outcomes were radiographic progression and safety.ResultsTCZ‐SC was superior to PBO‐SC for ACR20 response at week 24 (60.9% versus 31.5%; P < 0.0001). All secondary end points showed TCZ‐SC to be superior to PBO‐SC, including ACR50 and ACR70 response (40% and 20% for TCZ‐SC, respectively, and 12% and 5% for PBO‐SC, respectively; P < 0.0001 for both) and Disease Activity Score in 28 joints (DAS28) remission (DAS28 <2.6; 32% versus 4% [P < 0.0001]). The mean change in modified Sharp/van der Heijde score was significantly lower in the TCZ‐SC group than the PBO‐SC group (0.62 versus 1.23; P = 0.0149). Adverse events (AEs) and serious AEs (SAEs) were comparable between the TCZ‐SC and PBO‐SC groups; 4.6% and 3.7% of patients had at least 1 SAE, respectively, and infection was the most common SAE in 2.1% and 1.8% of patients, respectively. More injection site reactions occurred with TCZ‐SC than PBO‐SC (7.1% versus 4.1%). No anaphylaxis or serious hypersensitivity reactions occurred. There were 3 deaths in the TCZ‐SC group and 0 in the PBO‐SC group.ConclusionTCZ‐SC every other week had significantly greater efficacy, including ACR end points and inhibition of joint damage, compared with PBO‐SC. TCZ‐SC was well tolerated and its safety profile was comparable with that of previous intravenous TCZ studies.
Ein 2,6‐Bis(phenylamino)pyridinato‐Titan‐Katalysator für die hoch regioselektive Hydroaminoalkylierung von Styrolen und 1,3‐Butadienen
Authors: Dörfler Jaika , Preuß Till , Schischko Alexandra , Schmidtmann Marc , Doye Sven 
Published: June 2014

AbstractDie über eine C‐C‐Bindungsknüpfung verlaufende katalytische Hydroaminoalkylierung von terminalen Alkenen, 1,3‐Dienen und Styrolen ermöglicht eine direkte und zu 100 % atomökonomische Synthese von Aminen, bei der zwei Regioisomere (linear und verzweigt) gebildet werden können. Hier berichten wir über einen neuen Titan‐Katalysator mit 2,6‐Bis(phenylamino)pyridinato‐Liganden, in dessen Gegenwart die intermolekulare Hydroaminoalkylierung von Styrolen und 1‐Phenyl‐1,3‐butadienen mit exzellenten Regioselektivitäten zugunsten des linearen Produktes erreicht werden kann.
Brønsted‐Säure‐katalysierte konjugierte Addition von β‐Dicarbonylverbindungen an in situ erzeugte ortho‐Chinomethide – enantioselektive Synthese von 4‐Aryl‐4H‐chromenen
Authors: El‐Sepelgy Osama , Haseloff Stefan , Alamsetti Santosh Kumar , Schneider Christoph 
Published: June 2014

Abstract4H‐Chromene sind wichtige Strukturelemente vieler Naturstoffe und biologisch aktiver Verbindungen. Mithilfe einer enantioselektiven konjugierten Addition von β‐Diketonen an in situ erzeugte ortho‐Chinomethide gelingt nach dehydratisierender Cyclisierung eine breit anwendbare und hochselektive Synthese wertvoller 4‐Aryl‐4H‐chromene. Eine Binol‐basierte chirale Phosphorsäure wird zur In‐situ‐Erzeugung der ortho‐Chinomethide aus ortho‐Hydroxybenzhydrylalkoholen eingesetzt und katalysiert den C‐C‐bindungsbildenden Schritt.
Metallfreie Anellierung von Arenen mit 2‐Aminopyridin‐Derivaten: die Methylgruppe als spurlose nichtchelatisierende dirigierende Gruppe
Authors: Manna Srimanta , Matcha Kiran , Antonchick Andrey P. 
Published: June 2014

AbstractEine neue Anellierungsreaktion zwischen 2‐Aminopyridin‐Derivaten und Arenen unter metallfreien Bedingungen wurde beschrieben. Die intermolekulare Transformation ermöglicht den unkomplizierten Zugang zu dem wichtigen Pyrido[1,2‐a]benzimidazol‐Gerüst unter milden Reaktionsbedingungen. Über die beispiellose Anwendung der Methylgruppe von Methylbenzolen als spurlose nichtchelatisierende und hoch regiodirigierende Gruppe wird berichtet.
Multisite Organic–Inorganic Hybrid Catalysts for the Direct Sustainable Synthesis of GABAergic Drugs
Authors: Leyva‐Pérez Antonio , García‐García Pilar , Corma Avelino 
Published: June 2014

AbstractMultisite organic–inorganic hybrid catalysts have been prepared and applied in a new general, practical, and sustainable synthetic procedure toward industrially relevant GABA derivatives. The domino sequence is composed of seven chemical transformations which are performed in two one‐pot reactions. The method produces both enantiomeric forms of the product in high enantiopurity as well as the racemate in good yields after a single column purification step. This protocol highlights major process intensification, catalyst recyclability, and low waste generation.
Efficacy and Safety of Adalimumab as the First and Second Biologic Agent in Juvenile Idiopathic Arthritis: The German Biologics JIA Registry
Authors: Schmeling Heinrike , Minden Kirsten , Foeldvari Ivan , Ganser Gerd , Hospach Tony , Horneff Gerd 
Published: June 2014

ObjectiveTo evaluate the efficacy and safety of adalimumab in patients with juvenile idiopathic arthritis (JIA).MethodsBaseline demographic and clinical characteristics and disease activity parameters were prospectively documented in the German Biologics JIA Registry. Efficacy was determined using the American College of Rheumatology (ACR) Pediatric (Pedi) response criteria and the Juvenile Arthritis Disease Activity Score based on a 10‐joint count (JADAS‐10). Safety assessments were based on adverse event reports from the responsible physician.ResultsTwo hundred eighty‐nine patients with a total of 1,046 visits were identified (435.7 patient‐years). A high proportion of patients demonstrated a significant response to treatment, with a marked decrease in the JADAS‐10 score in both the biologics‐naive group (which consisted of patients who had not received therapy with a biologic agent prior to initiation of adalimumab) and the biologic‐switcher group (which consisted of patients who had been treated with a different biologic agent prior to initiation of adalimumab). The median JADAS‐10 score at treatment start was significantly higher in the biologics‐naive group than in the biologic‐switcher group (12.9 versus 8.5; P = 0.00044), although the score in the biologics‐naive group was lower over the course of adalimumab treatment. ACR Pedi 30, 50, 70, and 90 scores were achieved in 63.4%, 61.0%, 48.8%, and 34.2% of biologics‐naive patients, respectively, at 6 months of treatment, while ACR Pedi 30, 50, 70, and 90 scores were achieved in 47.6%, 38.1%, 21.9%, and 15.2% of biologic‐switcher patients, respectively. Forty‐eight patients experienced 222 adverse events (50.9 per 100 patient‐years). Eleven were reported as serious (2.5 per 100 patient‐years). No malignancies were observed during adalimumab exposure. There were 16 uveitis flares in 11 patients. Treatment was discontinued in 58 patients for the following reasons: inefficacy 11.1%, adverse events 5.2%, remission 4.5%, patient request 11.8%, and other reasons 7.9%.ConclusionAdalimumab appears to be highly effective in children and adolescents with JIA who have been previously treated with biologic agents and in children and adolescents who switched biologic agents. The treatment is safe and its efficacy is similar to that of other biologic agents used to treat JIA. Few patients discontinued therapy due to intolerance or inefficacy.
Herpes Zoster and Tofacitinib Therapy in Patients With Rheumatoid Arthritis
Authors: Winthrop Kevin L. , Yamanaka Hisashi , Valdez Hernan , Mortensen Eric , Chew Robert , Krishnaswami Sriram , Kawabata Thomas , Riese Richard 
Published: June 2014

ObjectivePatients with rheumatoid arthritis (RA) are at increased risk for herpes zoster (HZ) (i.e., shingles). The aim of this study was to determine whether treatment with tofacitinib increases the risk of HZ in patients with RA.MethodsHZ cases were identified as those reported by trial investigators from the databases of the phase II, phase III, and long‐term extension (LTE) clinical trials in the Tofacitinib RA Development Program. Crude incidence rates (IRs) of HZ per 100 patient‐years (with 95% confidence intervals [95% CIs]) were calculated by exposure group. Logistic regression analyses were performed to evaluate potential risk factors for HZ (e.g., age, prednisone use).ResultsAmong 4,789 participants, 239 were identified as having tofacitinib‐associated HZ during the phase II, phase III, and LTE trials, of whom 208 (87%) were female and whose median age was 57 years (range 21–75 years). One HZ case (0.4%) was multidermatomal; none of the cases involved visceral dissemination or death. Twenty‐four patients with HZ (10%) permanently discontinued treatment with tofacitinib, and 16 (7%) were either hospitalized or received intravenous antiviral drugs. The crude HZ IR across the development program was 4.4 per 100 patient‐years (95% CI 3.8–4.9), but the IR was substantially higher within Asia (7.7 per 100 patient‐years, 95% CI 6.4–9.3). Older age was associated with HZ (odds ratio 1.9, 95% CI 1.5–2.6), and IRs for HZ were similar between patients receiving 5 mg tofacitinib twice daily (4.4 per 100 patient‐years, 95% CI 3.2–6.0) and those receiving 10 mg twice daily (4.2 per 100 patient‐years, 95% CI 3.1–5.8). In the phase III trials among placebo recipients, the incidence of HZ was 1.5 per 100 patient‐years (95% CI 0.5–4.6).ConclusionIn the Tofacitinib RA Development Program, increased rates of HZ were observed in patients treated with tofacitinib compared with those receiving placebo, particularly among patients within Asia. Complicated HZ among tofacitinib‐treated patients was rare.
Das Wissen der Schulden. Recht, Kulturtechnik und Alltagserfahrung im liberalen Kapitalismus
Authors: Suter Mischa 
Published: June 2014

AbstractThe Knowledge of Debt: Law, Media Technique, and Everyday Experience in Liberal Capitalism. Performing an object such as ‘the economy’ hinges on practices of formatting knowledge. The article proposes to look at such instituting moments in connection with social conflicts over the legitimate rules of exchange. This is exemplified by way of recounting the story of the codification of Swiss bankruptcy law in 1889. In order to homogenize the legal procedures of debt collection and bankruptcy, two subject categories were instituted: ‘merchants’ and ‘non‐merchants’. These different categories were thought to account for the diverging temporalities and spaces of credit exchange in everyday economic life. The introduction of the commercial register, a media‐technical apparatus, enabled a formal distinction between ‘merchants’ and ‘non‐merchants’. However, this boundary was contested and proved to be porose.
Hexacyanoferrate‐adapted biofilm enables the development of a microbial fuel cell biosensor to detect trace levels of assimilable organic carbon (AOC) in oxygenated seawater
Authors: Cheng Liang , Quek Soon Bee , Cord‐Ruwisch Ralf 
Published: June 2014

ABSTRACTA marine microbial fuel cell (MFC) type biosensor was developed for the detection of assimilable organic carbon (AOC) in ocean water for the purpose of online water quality monitoring for seawater desalination plants prone to biofouling of reverse osmosis (RO) membranes. The anodophilic biofilm that developed on the graphite tissue anode could detect acetate as the model AOC to concentrations as low as 5 µM (120 µg/L of AOC), which is sufficiently sensitive as an online biofouling risk sensor. Although the sensor was operated at a higher (+200 ± 10 mV) than the usual (‐300 mV) anodic potential, the presence of oxygen completely suppressed the electrical signal. In order to overcome this outcompeting effect of oxygen over the anode as electron acceptor by the bacteria, hexacyanoferrate (HCF(III)) was found to enable the development of an adapted biofilm that transferred electrons to HCF(III) rather than oxygen. As the resultant of the reduced HCF(II) could readily transfer electrons to the anode while being re‐oxidised to HCF(III), the marine MFC biosensor developed could be demonstrated to work in the presence of oxygen unlike traditional MFC. The possibility of operating the marine MFC in batch or continuous (in‐line) mode has been explored by using coulombic or potentiometric interpretation of the signal. Biotechnol. Bioeng. 2014;111: 2412–2420. © 2014 Wiley Periodicals, Inc.
Unrelated solubility‐enhancing fusion partners MBP and NusA utilize a similar mode of action
Authors: Raran‐Kurussi Sreejith , Waugh David S. 
Published: June 2014

ABSTRACTThe tendency of recombinant proteins to accumulate in the form of insoluble aggregates in Escherichia coli is a major hindrance to their overproduction. One of the more effective approaches to circumvent this problem is to use translation fusion partners {solubility‐enhancers (SEs)}. E. coli maltose‐binding protein (MBP) and N‐utilization substance A (NusA) are arguably the most effective solubilizing agents that have been discovered so far. Here, we show that although these two proteins are structurally, functionally, and physicochemically distinct, they influence the solubility and folding of their fusion partners in a very similar manner. These SEs act as “holdases” that prevent the aggregation of their fusion partners. Subsequent folding of the passenger proteins, when it occurs, is either spontaneous or chaperone‐mediated. Biotechnol. Bioeng. 2014;111: 2407–2411. © 2014 Wiley Periodicals, Inc.
Structure‐Based Design of New KSP‐Eg5 Inhibitors Assisted by a Targeted Multicomponent Reaction
Authors: Carbajales Carlos , Prado Miguel Ángel , Gutiérrez‐de‐Terán Hugo , Cores Ángel , Azuaje Jhonny , Novio Silvia , Nuñez María Jesús , Fernández‐García Belén , Sotelo Eddy , García‐Mera Xerardo , Sánchez‐Lazo Pedro , Freire‐Garabal Manuel , Coelho Alberto 
Published: June 2014

AbstractAn integrated multidisciplinary approach that combined structure‐based drug design, multicomponent reaction synthetic approaches and functional characterization in enzymatic and cell assays led to the discovery of new kinesin spindle protein (KSP) inhibitors with antiproliferative activity. A focused library of new benzimidazoles obtained by a Ugi+Boc removal/cyclization reaction sequence generated low‐micromolar‐range KSP inhibitors as promising anticancer prototypes. The design and functional studies of the new chemotypes were assessed by computational modeling and molecular biology techniques. The most active compounds—20 (IC50=1.49 μM, EC50=3.63 μM) and 22 (IC50=1.37 μM, EC50=6.90 μM)—were synthesized with high efficiency by taking advantage of the multicomponent reactions.
Calprotectin induces cell death in human prostate cancer cell (LNCaP) through survivin protein alteration
Authors: Sattari Mina , Pazhang Yaghub , Imani Mehdi 
Published: June 2014

AbstractCalprotectin (CP), an abundant heterodimeric cytosolic protein of neutrophils, conveys a variety of functions such as tumor cell growth arrest and antimicrobial activity. We investigated CP activity and its possible apoptosis‐inducing mechanism of action against an antiandrogen therapy‐resistance prostate cancer cell line LNCaP. Cell viability and Annexin V FITC assays were performed in order to investigate its cell death activity and apoptosis, respectively. In order to address cell death inducing mechanism(s), immunocytochemistry and immunobloting analysis, reactive oxygen species (ROS) and nitric oxide (NO) measurements were performed. The effective concentration of CP against LNCaP promoting LNCaP cell death was 200 µg/mL. ROS and NO levels of cells remarkably were enhanced following treatment with 50 and 100 µg/mL of CP, respectively. Protein expression of anti‐apoptotic protein survivin was significantly decreased after administration of tumor cells with CP. Our data indicate that CP regulates the LNCaP cells viability via survivin‐mediated pathway and ROS and NO enhancement. Thus, inhibition of survivin expression, enhancement of ROS and NO level by CP or other similar pharmaceutical agents might be effective in lowering the malignant proliferation of human prostate cancer cells.
Long‐term recurrence of soft tissue sarcomas: Prognostic factors and implications for prolonged follow‐up
Authors: Toulmonde Maud , Le Cesne Axel , Mendiboure Jean , Blay Jean‐Yves , Piperno‐Neumann Sophie , Chevreau Christine , Delcambre Corinne , Penel Nicolas , Terrier Philippe , Ranchère‐Vince Dominique , Lae Marick , Le Guellec Sophie , Michels Jean‐Jacques , Robin Yves‐Marie , Bellera Carine , Italiano Antoine 
Published: June 2014

BACKGROUNDTo the authors' knowledge, the incidence of late recurrence (> 5 years after initial management) is unknown and no prognostic factors for late events have been characterized in patients with soft tissue sarcomas.METHODSFollow‐up data from patients with localized soft tissue sarcoma who were included in the French Sarcoma Group database from January 1990 to June 2005 were reviewed. The outcomes of interest were the cumulative probabilities of late (> 5 years) local and metastatic disease recurrence with death as a competing event. Estimations and 95% confidence intervals (95% CIs) were computed with the cumulative incidence function.RESULTSA total of 719 patients who were alive and event free > 5 years after their initial diagnosis were included in the current study. Sixty‐seven patients (9.3%) developed a late local recurrence and 42 patients (5.8%) developed a late metastatic recurrence, respectively. On multivariate analysis, internal trunk location (hazard ratio [HR], 3.9; 95% CI, 2.2‐6.7 [P < .001]) and tumor size > 100 mm (HR, 2.1; 95% CI, 1.1‐4 [P = .035]) were the 2 factors found to be independently associated with an increased risk of late local recurrence. Grade > 1 (graded according to the French Federation of Cancer Centers Sarcoma Group) (HR, 4.7; 95% CI 1.1‐21 [P = .04]) was the sole factor found to be independently associated with an increased risk of late metastatic recurrence.CONCLUSIONSLate recurrence of soft tissue sarcoma is relatively uncommon. However, the results of the current study emphasize the critical role of long‐term follow‐up to detect late local disease recurrence in patients with retroperitoneal or very large soft tissue sarcomas, and late metastatic recurrence in patients with high‐grade disease. Conversely, the prolonged follow‐up of patients with grade 1 disease is not needed. Cancer 2014;120:3003–3006. © 2014 American Cancer Society.