bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenicity of Lupus Anti–Ribosomal P Antibodies: Role of Cross‐Reacting Neuronal Surface P Antigen in Glutamatergic Transmission and Plasticity in a Mouse Model
Authors: Segovia‐Miranda Fabián , Serrano Felipe , Dyrda Agnieszka , Ampuero Estibaliz , Retamal Claudio , Bravo‐Zehnder Marcela , Parodi Jorge , Zamorano Pedro , Valenzuela David , Massardo Loreto , van Zundert Brigitte , Inestrosa Nibaldo C. , González Alfonso
Published: February 2015

Objective

To assess whether autoantibodies against ribosomal P (anti‐P), which are possibly pathogenic in neuropsychiatric systemic lupus erythematosus (NPSLE), alter glutamatergic synaptic transmission and to what extent the cross‐reacting neuronal surface P antigen (NSPA) is involved.

Methods

We analyzed glutamatergic transmission and long‐term potentiation (LTP) mediated by AMPA receptor (AMPAR) and N‐methyl‐d‐aspartate receptor (NMDAR) by field excitatory postsynaptic potential (EPSP) at the CA3–CA1 synapse. AMPAR activation by patch‐clamp recordings in primary ventral spinal cord neurons was analyzed. In primary hippocampal neurons, NSPA distribution was assessed by double immunofluorescence, and intracellular calcium changes were evaluated using Fura‐2 AM. NSPA‐LacZ reporter–knockin mice expressing a truncated NSPA were used to assess NSPA expression pattern and function in the brain using β‐galactosidase staining and comparative electrophysiology, calcium responses, and water maze memory tests.

Results

NSPA was expressed in the brain in hippocampal CA1, dentate gyrus and ventral, but not dorsal, CA3 regions, encompassing postsynaptic regions and partial colocalization with NMDAR. Notably, NSPA‐LacZ reporter–knockin mice showed impaired memory, and decreased NMDAR activity and LTP, with neurons insensitive to anti‐P autoantibodies. Anti‐P autoantibodies enhanced CA1 postsynaptic transmission, increasing AMPAR and NMDAR activity and leading to LTP abrogation after prolonged (20‐minute) incubation.

Conclusion

Our findings indicate that the neuronal cell surface target of anti‐P, NSPA, is involved in glutamatergic synaptic transmission and plasticity related to memory in the hippocampus, and mediates the deleterious effects of anti‐P on these processes. Cognitive impairment, as well as other diffuse NPSLE manifestations, may develop when anti‐P autoantibodies have access to brain regions coexpressing NSPA, AMPAR, and NMDAR.
Brief Report: Responses to Rituximab Suggest B Cell–Independent Inflammation in Cutaneous Systemic Lupus Erythematosus
Authors: Vital Edward M. , Wittmann Miriam , Edward Sara , Md Yusof Md Yuzaiful , MacIver Helen , Pease Colin T. , Goodfield M. , Emery Paul
Published: February 2015

Objective

The immunopathogenesis of systemic lupus erythematosus (SLE) is heterogeneous, and responses of skin to rituximab are variable. This study was undertaken to determine the phenotype of rituximab‐responsive disease.

Methods

Eighty‐two patients with SLE who were receiving rituximab were prospectively studied. Of these patients, 32 had significant skin involvement before or after treatment. Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) index 2004. Cutaneous lupus subtype was classified by a dermatologist as acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), chronic cutaneous lupus erythematosus (CCLE), or other skin diseases, with supportive photographs or biopsies where necessary.

Results

Of 26 patients with skin disease at baseline, 9 (35%) had a beneficial mucocutaneous response to rituximab at 6 months, with good responses in ACLE (6 of 14 patients [43%]), and poor responses in CCLE (0 of 8 patients) (P = 0.034). Clinical response was associated with anti‐RNP negativity (P = 0.024) and anti‐Ro negativity (P = 0.031). Flares of SCLE and CCLE occurred in 12 patients who either had no skin disease or had ACLE at baseline (i.e., a switch in subtype). Concomitant antimalarials or conventional immunosuppressants were not associated with response or flare rate. Posttreatment biopsies confirmed typical active SLE histology in lesions occurring during B cell depletion.

Conclusion

Our findings indicate that the clinical response to rituximab in cutaneous manifestations of SLE depends on subtype. None of the CCLE patients responded, and new CCLE lesions were observed during B cell depletion, suggesting that initiation and activity of these lesions is not B cell dependent. Flares of a range of skin diseases after B cell depletion may indicate a change in immune regulation following B cell–targeted therapy.
Pre‐exposure of neuroblastoma cell line to pulsed electromagnetic field prevents H2O2‐induced ROS production by increasing MnSOD activity
Authors: Osera Cecilia , Amadio Marialaura , Falone Stefano , Fassina Lorenzo , Magenes Giovanni , Amicarelli Fernanda , Ricevuti Giovanni , Govoni Stefano , Pascale Alessia
Published: February 2015

Electromagnetic fields (EMFs) have been linked to increased risk of cancers and neurodegenerative diseases; however, EMFs can also elicit positive effects on biological systems, and redox status seems crucially involved in EMF biological effects. This study aimed to assess whether a short and repeated pulsed EMF (PEMF) could trigger adaptive responses against an oxidative insult in a neuronal cellular model. We found that a 40 min overall (four times a week, 10 min each) pre‐exposure to PEMF did not affect major physiological parameters and led to a significant increase of Mn‐dependent superoxide dismutase activity in the human neuroblastoma SH‐SY5Y cell line. In addition, we found PEMF‐pre‐exposed cells exhibited decreased reactive oxygen species production following a 30 min H2O2 challenge, with respect to non pre‐exposed cells. Our findings might provide new insights on the role played by short and repeated PEMF stimulations in the enhancement of cellular defenses against oxidative insults. Although studies in normal neuronal cells would be useful to further confirm our hypothesis, we suggest that specific PEMF treatments may have potential biological repercussions in diseases where oxidative stress is implicated. Bioelectromagnetics. Bioelectromagnetics. 36:219–232, 2015. © 2015 Wiley Periodicals, Inc.
Incidental findings in surgery
Authors: Anderson L , Snelling J , van Rij A
Published: February 2015

Guidance for a complex issue
Orthogonal Translation Meets Electron Transfer: In Vivo Labeling of Cytochrome c for Probing Local Electric Fields
Authors: Völler Jan , Biava Hernan , Koksch Beate , Hildebrandt Peter , Budisa Nediljko
Published: February 2015

Cytochrome c (cyt c), a redox protein involved in diverse fundamental biological processes, is among the most traditional model proteins for analyzing biological electron transfer and protein dynamics both in solution and at membranes. Studying the role of electric fields in energy transduction mediated by cyt c relies upon appropriate reporter groups. Up to now these had to be introduced into cyt c by in vitro chemical modification. Here, we have overcome this restriction by incorporating the noncanonical amino acid p‐cyanophenylalanine (pCNF) into cyt c in vivo. UV and CD spectroscopy indicate preservation of the overall protein fold, stability, and heme coordination, whereas a small shift of the redox potential was observed by cyclic voltammetry. The C≡N stretching mode of the incorporated pCNF detected in the IR spectra reveals a surprising difference, which is related to the oxidation state of the heme iron, thus indicating high sensitivity to changes in the electrostatics of cyt c.
Mental disorder, imprisonment and reduced life expectancy – A nationwide psychiatric inpatient cohort study
Authors: Steingrimsson Steinn , Sigurdsson Martin I. , Gudmundsdottir Hafdis , Aspelund Thor , Magnusson Andres
Published: February 2015

Background

There is a strong correlation between severe mental illness and criminality, but little is known about how these two problem areas together may affect health outcomes.

Aim

The objective of this paper is to compare survival rates of male psychiatric inpatients over a 25‐year period who have and have not been subject to imprisonment, allowing for nature of psychiatric morbidity.

Methods

A nationwide cohort of men who had ever been psychiatric inpatients was identified from Icelandic data‐registers, and their diagnoses after first discharge, cumulative incidence of imprisonment, and mortality established from records. Using a nested case‐control design, survival differences were determined between those ever imprisoned and those never imprisoned.

Results

Between January 1983 and March 2008, 7665 men were admitted to psychiatric wards in Iceland, of whom 812 (10.6%) had served a prison sentence during that time. Cumulative incidence of imprisonment was highest in the youngest age group (21%). Substance use and personality disorders were more common amongst those imprisoned. All‐cause mortality, adjusted for diagnosis, age, and year of admission, was twice as high amongst those imprisoned as those not imprisoned (Hazard ratio = 2.0, 95% CI 1.5–2.6, p < 0.001).

Clinical implications

Our findings indicate that psychiatric inpatients with criminal records should receive special attention with respect to all aspects of their health, not only within psychiatric services but also through more collaboration between the healthcare and judicial systems. Copyright © 2015 John Wiley & Sons, Ltd.
Synthesis and Composition‐Dependent Visible Photocatalysis of Ag/AgBr Necklace‐Like Heterostructures
Authors: Li Xiaoyu , Zhang Xiao , Jia Changchao , Matras‐Postolek Katarzyna , Yang Ping
Published: February 2015

A two‐step synthesis was developed to fabricate Ag/AgBr necklace‐like nano‐heterostructures at room temperature. Multiple crystalline Ag nanowires were used as templates following an oxidation route in situ from CuBr2 to create Ag/AgBr heterostructures. Polyvinylpyrrolidone can govern the formation of one‐dimensional Ag/AgBr necklace‐like nano‐heterostructures. The composition of the heterostructures was adjusted by changing the amount of CuBr2. Experimental conditions were optimized. In particular, the concentration and injection rate of copper bromide solution play an important role in controlling the oxidation of the Ag nanowires for the purpose of adjusting the morphology of the Ag/AgBr heterostructures. As a result, the heterostructures with 40 mol % AgBr displayed a regular necklace‐like morphology. Under visible‐light irradiation, Ag/AgBr necklace‐like heterostructures with AgBr molar ratios of 10 to 50 % exhibited enhanced plasmonic photocatalytic performance for the degradation of organic pollutants (methyl orange, methylene blue, and rhodamine B).
Room Temperature Organocatalyzed Reductive Depolymerization of Waste Polyethers, Polyesters, and Polycarbonates
Authors: Feghali Elias , Cantat Thibault
Published: February 2015

The reductive depolymerization of a variety of polymeric materials based on polyethers, polyesters, and polycarbonates is described using hydrosilanes as reductants and metal‐free catalysts. This strategy enables the selective depolymerization of waste polymers as well as bio‐based polyesters to functional chemicals such as alcohols and phenols at room temperature. Commercially available B(C6F5)3 and [Ph3C+,B(C6F5)4−] catalysts are active hydrosilylation catalysts in this procedure and they are compatible with the use of inexpensive and air‐stable polymethylhydrosiloxane and tetramethyldisiloxane as reductants. A significant advantage of this recycling method is derived from its tolerance to the additives present in waste plastics and its ability to selectively depolymerize mixtures of polymers.
Loss in body weight is an independent prognostic factor for mortality in chronic heart failure: insights from the GISSI‐HF and Val‐HeFT trials
Authors: Rossignol Patrick , Masson Serge , Barlera Simona , Girerd Nicolas , Castelnovo Angelo , Zannad Faiez , Clemenza Francesco , Tognoni Gianni , Anand Inder S. , Cohn Jay N. , Anker Stefan D. , Tavazzi Luigi , Latini Roberto ,   on the behalf of GISSI‐HF and Val‐HeFT Investigators
Published: February 2015

Aims

Uncertainties remain on the biological and prognostic significance and therapeutic implications of loss in body weight (W‐LOSS) in chronic heart failure (HF) patients. We assessed whether W‐LOSS added additional prognostic value to classical clinical risk factors in two separate and large cohorts of patients with chronic HF. The factors associated with W‐LOSS were studied.

Methods and results

W‐LOSS and estimated plasma volume changes were measured serially in the GISSI‐HF (n = 6820) and Val‐HeFT trials (n = 4892). In both studies, experiencing at least one episode of ≥5% W‐LOSS during the first year of follow‐up was considered a sign of wasting. In GISSI‐HF, self‐reported unintentional W‐LOSS ≥2 kg between two consecutive clinical visits within 1 year was also considered a sign of wasting. W‐LOSS occurred in 16.4% and 15.7% of the patients enrolled in GISSI‐HF and Val‐HeFT, respectively (unintentional ≥2 kg W‐LOSS occurred in 18.9% in GISSI‐HF). In multivariable analyses adjusting for a number of baseline covariates as well as for plasma volume changes, W‐LOSS was found to be independently associated with mortality and adverse cardiovascular and non‐cardiovascular outcomes, with a significant net reclassification improvement (cfNRI) and an increase in integrated discrimination improvement (IDI). W‐LOSS was independently associated with several features representing the severity of HF, including baseline NT‐proBNP and high sensitivity C‐reactive protein (hsCRP) in Val‐HeFT.

Conclusions

W‐LOSS was a frequent finding in the GISSI‐HF and Val‐HeFT trials, associated with multiple patient features, and added additional prognostic information beyond clinical variables of HF severity, including estimated plasma volume changes.
Sympathetic nervous system activation and β‐adrenoceptor blockade in right heart failure
Authors: Andersen Stine , Andersen Asger , de Man Frances S. , Nielsen‐Kudsk Jens E.
Published: February 2015

Right heart failure may develop from pulmonary arterial hypertension or various forms of congenital heart disease. Right ventricular adaptation to the increased afterload is the most important prognostic factor in pulmonary hypertension and congenital heart disease, which share important pathophysiological mechanisms, despite having different aetiologies. There is substantial evidence of increased sympathetic nervous system activation in right heart failure related to both pulmonary hypertension and congenital heart disease. It is unknown to which degree this activation is an adaptive response, a maladaptive response, or if it mainly reflects disease progression. Several experimental studies and clinical trials have been conducted to answer these questions. Here, we review the existing knowledge on sympathetic nervous system activation and the effects of β‐adrenoceptor blockade in experimental and clinical right heart failure. This review identifies important gaps in our understanding of the right ventricle and discusses the potential of β‐blockers in the treatment of right heart failure.
Resveratrol‐loaded liposomes: Interaction of resveratrol with phospholipids
Authors: Balanč Bojana D. , Ota Ajda , Djordjević Verica B. , Šentjurc Marjeta , Nedović Viktor A. , Bugarski Branko M. , Ulrih Nataša Poklar
Published: February 2015

The influence of resveratrol encapsulated into liposomes (prepared with a commercial lipid mixture of phospholipids, phospolipon 90NG, using the thin film and proliposome methods) on the structural properties of the liposome membrane was investigated by electron paramagnetic resonance (EPR) spectroscopy, fluorescence spectroscopy, and differential scanning calorimetry. Two fluorophores and two spin probes were used to monitor the characteristics of membranes made from a commercial mixture of phosphatidylcholine. Resveratrol was positioned rather in the inner part of the liposome membranes causing reduction in membrane fluidity. Moreover, resveratrol induced a concentration‐dependent decrease in the gel‐to‐liquid crystalline phase transition temperature (from 41.3 to 38.3°C, for a saturated 1,2‐dipalmitoyl‐sn‐glycero‐3‐phospatidylcholine bilayer). The antioxidant activity of resveratrol was confirmed by its 95% inhibition of lipid peroxidation, compared to liposomes without resveratrol exposed to the same conditions. Similarly, EPR spectroscopy spin trapping showed an 87% reduction in the spectra intensity of the hydroxyethyl radical, which indicates the efficiency of resveratrol for inhibition of OH radical production.

Practical applications: Resveratrol is in the limelight all over the world as a health‐beneficial compound widely investigated as natural antioxidant suitable for prevention of human cardiovascular diseases and inhibition of low‐density lipoproteins oxidation. Public interest in prevention of diseases through enriched staple foods grows each day. Nonetheless, addition of antioxidants to aqueous‐based food can be limited due to their troublesome characteristics. Liposomes are nanocarriers that may be used to overcome the disadvantages and they can be used for food applications. Liposomes could be prepared using only natural components and therefore the new formulations could be quickly implemented. Still, the application of liposomes in food systems is not widespread due to time consuming manufacturing processes and high costs. The presented results provide marks and suggestions to food manufacturers and scientists on how to make broader use of resveratrol‐loaded liposomes which add value and improve the quality of existing food products.

The influence of resveratrol encapsulated into liposomes (prepared using the thin film and proliposome methods) on the structural properties of the liposome membrane was investigated by electron paramagnetic resonance spectroscopy, fluorescence spectroscopy, and differential scanning calorimetry. The antioxidant activity of resveratrol was confirmed by its inhibition of lipid peroxidation and by spin trapping.
Contradiction between the C‐property and mass conservation in adaptive grid based shallow flow models: cause and solution
Authors: Liang Qiuhua , Hou Jingming , Xia Xilin
Published: February 2015

When performing shallow flow simulations on adaptive grids, the C‐property (i.e. conservation property) and the mass conservation may not be simultaneously preserved, that is, either C‐property or mass conservation is likely to be violated following grid refining or coarsening. The cause of such a contradiction is analyzed in detail in this work, which essentially links to the reconstruction of bed and flow information in those newly created cells during grid adaptation. An effective approach is subsequently proposed to resolve the contradiction by locally modifying the bed elevation in certain problematic cells when reconstructing flow information using linear interpolation as part of the grid adaptation procedure. Copyright © 2015 John Wiley & Sons, Ltd.
A robust and well‐balanced scheme for the 2D Saint‐Venant system on unstructured meshes with friction source term
Authors: Duran A.
Published: February 2015

In the following lines, we propose a numerical scheme for the shallow‐water system supplemented by topography and friction source terms, in a 2D unstructured context. This work proposes an improved version of the well‐balanced and robust numerical model recently introduced by Duran et al. (J. Comp. Phys., 235, 565–586, 2013) for the pre‐balanced shallow‐water equations, accounting for varying topography. The present work aims at relaxing the robustness condition and includes a friction term. To this purpose, the scheme is modified using a recent method, entirely based on a modified Riemann solver. This approach preserves the robustness and well‐balanced properties of the original scheme and prevents unstable computations in the presence of low water depths. A series of numerical experiments are devoted to highlighting the performances of the resulting scheme. Simulations involving dry areas, complex geometry and topography are proposed to validate the stability of the numerical model in the neighbourhood of wet/dry transitions. Copyright © 2015 John Wiley & Sons, Ltd.
Sox12, a direct target of FoxQ1, promotes hepatocellular carcinoma metastasis through up‐regulating Twist1 and FGFBP1
Authors: Huang Wenjie , Chen Zhangqian , Shang Xin , Tian Dean , Wang Daowen , Wu Kaichun , Fan Daiming , Xia Limin
Published: February 2015

Metastasis is the main reason for high recurrence and poor survival of hepatocellular carcinoma (HCC) after curative resection. However, the molecular mechanism underlying HCC metastasis remains unclear. Here, we report on a novel function of SRY (sex determining region Y)‐box 12 (Sox12), a member of the SYR‐related high mobility group box family proteins, in promoting HCC metastasis. Overexpression of Sox12 was significantly correlated with loss of tumor encapsulation, microvascular invasion, and a higher tumor‐nodule‐metastasis (TNM) stage and indicated poor prognosis in human HCC patients. Sox12 expression was an independent and significant risk factor for recurrence and reduced survival after curative resection. Overexpression of Sox12 induced epithelial‐mesenchymal transition by transactivating Twist1 expression. Down‐regulation of Twist1 decreased Sox12‐enhanced HCC migration, invasion, and metastasis, whereas up‐regulation of Twist1 rescued the decreased migration, invasion, and metastasis induced by Sox12 knockdown. Additionally, serial deletion, site‐directed mutagenesis, and chromatin immunoprecipitation assays showed that fibroblast growth factor binding protein 1 (FGFBP1) was a direct transcriptional target of Sox12. Knockdown of FGFBP1 decreased Sox12‐mediated HCC invasion and metastasis, whereas overexpression of FGFBP1 rescued the decreased invasion and metastasis induced by Sox12 knockdown. Furthermore, forkhead box Q1 (FoxQ1) directly bound to the Sox12 promoter and transactivated its expression, which contributed to Sox12 overexpression in human HCC. Knockdown of Sox12 dramatically decreased FoxQ1‐mediated HCC metastasis. In two independent cohorts of human HCC tissues, Sox12 expression was positively correlated with Twist1, FGFBP1, and FoxQ1 expression, and patients with positive coexpression of Sox12/Twist1, Sox12/FGFBP1, or FoxQ1/Sox12 were associated with poorer prognosis. Conclusion: Up‐regulated Sox12 induced by FoxQ1 promotes HCC invasion and metastasis by transactivating Twist1 and FGFBP1 expression. Thus, our study implicates Sox12 as a potential prognostic biomarker and a novel therapeutic target for HCC. (Hepatology 2015;61:1920–1933)
Electronic structure and microscopic charge‐transport properties of a new‐type diketopyrrolopyrrole‐based material
Authors: Huang Jin‐Dou , Li Wen‐Liang , Wen Shu‐Hao , Dong Bin
Published: February 2015

Recently, diketopyrrolopyrrole (DPP)‐based materials have attracted much interest due to their promising performance as a subunit in organic field effect transistors. Using density functional theory and charge‐transport models, we investigated the electronic structure and microscopic charge transport properties of the cyanated bithiophene‐functionalized DPP molecule (compound 1). First, we analyzed in detail the partition of the total relaxation (polaron) energy into the contributions from each vibrational mode and the influence of bond‐parameter variations on the local electron–vibration coupling of compound 1, which well explains the effects of different functional groups on internal reorganization energy (λ). Then, we investigated the structural and electronic properties of compound 1 in its isolated molecular state and in the solid state form, and further simulated the angular resolution anisotropic mobility for both electron‐ and hole‐transport using two different simulation methods: (i) the mobility orientation function proposed in our previous studies (method 1); and (ii) the master equation approach (method 2). The calculated electron‐transfer mobility (0.00003–0.784 cm2 V−1 s−1 from method 1 and 0.02–2.26 cm2 V−1 s−1 from method 2) matched reasonably with the experimentally reported value (0.07–0.55 cm2 V−1 s−1). To the best of our knowledge, this is the first time that the transport parameters of compound 1 were calculated in the context of band model and hopping models, and both calculation results suggest that the intrinsic hole mobility is higher than the corresponding intrinsic electron mobility. Our calculation results here will be instructive to further explore the potential of other higher DPP‐containing quinoidal small molecules. © 2015 Wiley Periodicals, Inc.
Assessments of antibody biodistribution
Authors: Glassman Patrick M. , Abuqayyas Lubna , Balthasar Joseph P.
Published: February 2015

Monoclonal antibody (mAb) therapeutics are in use for several disease conditions, and have generally shown excellent clinical benefit, in large part due to their high specificity and affinity for target proteins. As this therapeutic class continues to grow in size, improved understanding of the mechanisms controlling mAb biodistribution and protein binding may be expected to allow better prediction of safety and efficacy. Due to the large size and polarity of antibodies, rates of mAb distribution and elimination are typically much slower than those reported for small molecule drugs. Additionally, high affinity interaction with target proteins will often influence mAb pharmacokinetics, leading to complex, nonlinear tissue distribution and elimination. In this report, we summarize key determinants of mAb disposition, methods for assessing antibody exposure and protein binding, and model‐based approaches that may be utilized to predict mAb pharmacokinetics.
Dashboard systems: Pharmacokinetic/pharmacodynamic mediated dose optimization for monoclonal antibodies
Authors: Mould Diane R. , Dubinsky Marla C.
Published: February 2015

Many marketed drugs exhibit high variability in exposure and response. While these drugs are efficacious in their approved indications, finding appropriate dose regimens for individual patients is not straightforward. Similar dose adjustment problems are also seen with drugs that have a complex relationship between exposure and response and/or a narrow therapeutic window. This is particularly true for monoclonal antibodies, where prolonged dosing at a sub‐therapeutic dose can also elicit anti‐drug antibodies which will further compromise safety and efficacy. Thus, finding appropriate doses quickly would represent a substantial improvement in healthcare. Dashboard systems, which are decision‐support tools, offer an improved, convenient means of tailoring treatment for individual patients. This article reviews the clinical need for this approach, particularly with monoclonal antibodies, the design, development, and testing of such systems, and the likely benefits of dashboard systems in clinical practice. We focus on infliximab for reference.
Pharmacokinetics of anti‐TNF monoclonal antibodies in inflammatory bowel disease: Adding value to current practice
Authors: Vande Casteele Niels , Gils Ann
Published: February 2015

Since anti‐tumor necrosis factor (TNF) antibodies were introduced to treat patients with inflammatory bowel diseases, short‐ and long‐term clinical and endoscopic endpoints can be achieved that were unreachable with conventional anti‐inflammatory agents. Although a large proportion of patients (70–90%) initially respond to the treatment, remission rates after induction are still low (20–50%) and patients are at risk to lose response to the drug over time. This inter‐individual variability in response is likely to be influenced by the observed inter‐individual variability in pharmacokinetics. By extensively reviewing the literature, we evaluated the potential role of therapeutic drug monitoring to optimize dosing of anti‐TNF drugs. Thereby we emphasize some of the pharmacokinetic cornerstones that can help to understand the observed concentration–effect relationship. After discussing some of the most commonly used assays to measure anti‐TNF drug and anti‐drug antibody concentrations, we reviewed the application of those tests and their potential clinical value in retrospective and prospective studies.
Ultrasound diagnosis of serous surface papillary borderline ovarian tumor: A case series with a review of the literature
Authors: Ludovisi Manuela , Foo Xulin , Mainenti Sara , Testa Antonia Carla , Arora Rupali , Jurkovic Davor
Published: February 2015

Serous surface papillary borderline ovarian tumors (SSPBOTs) are a rare morphologic variant of serous ovarian tumors that are typically confined to the ovarian surface, while the ovaries themselves tend to appear normal in size and shape. In this report, we describe the findings from five premenopausal women diagnosed with SSPBOTs, in whom ultrasound showed grossly normal ovaries that were partially or wholly covered with irregular solid tumors. In all five cases, histologic examination showed evidence of borderline serous tumors. These findings demonstrate that SSPBOTs can be diagnosed on a preoperative sonographic examination, which could facilitate conservative, fertility‐sparing surgery in young women affected by this condition. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 43:573–577, 2015
Natural Product‐Mimetic Scaffolds with Privileged Heterocyclic Systems: Design, Synthesis, and Evaluation of Antioxidant Activity of Quinazoquinobenzothiazinones
Authors: Sharma Kshitija , Khandelwal Sarita , Samarth R. M. , Kumar Mahendra
Published: February 2015

Structurally diverse quinazolinoquinolinobenzothiazinones based on rutaecarpine structural framework with hybrid structural features of three medicinally privileged heterocyclic systems has been synthesized as natural product‐mimetic scaffolds involving the use of multi‐step reaction sequences. The synthesized quinazolinoquinolinobenzothiazinones have been evaluated for their antioxidant and radical scavenging activities.
Brain changes associated with thromboxane receptor antagonist SQ 29,548 treatment in a mouse model
Authors: Rebel Andrew A. , Urquhart Siri A. , Puig Kendra L. , Ghatak Atreyi , Brose Stephen A. , Golovko Mikhail Y. , Combs Colin K.
Published: February 2015

The purpose of this study was to characterize behavioral and physiological effects of a selective thromboxane (TP) receptor antagonist, SQ 29,548, in the C57Bl/6 mouse model. At 6 months of age, male mice were given either sham or drug i.p. injections for 3 days at a dose of 2 mg/kg each day. On the day after the final injection, mice were subjected to behavioral testing before brain collection. Left hemisphere hippocampi were collected from all mice for protein analysis via Western blot. Right brain hemispheres were fixed and embedded in gelatin and then serially sectioned. The sections were immunostained with anti‐c‐Fos antibodies. Prostaglandin analysis was performed from remaining homogenized brain samples, minus the hippocampi. Injection of SQ 29,548 decreased selective brain prostaglandin levels compared with sham controls. This correlated with robust increases in limbic‐region c‐Fos immunoreactivity in the SQ 29,548‐injected mice. However, drug‐treated mice demonstrated no significant changes in relevant hippocampal protein levels compared with sham treatments, as determined from Western blots. Surprisingly, injection of SQ 29,548 caused mixed changes in parameters of depression and anxiety‐like behavior in the mice. In conclusion, the results indicate that administration of peripheral TP receptor antagonists alters brain levels of prostanoids and influences neuronal activity, with only minimal alterations of behavior. Whether the drug affects neurons directly or through a secondary pathway involving endothelium or other tissues remains unclear. © 2015 Wiley Periodicals, Inc.
A Primer in Resiliency: Seven Principles for Managing the Unexpected
Authors: Seville Erica , Van Opstal Debra , Vargo John
Published: February 2015

For business organizations, the ability to manage volatility is a crucial strategic competency, one of the pillars of competitiveness. Contrary to conventional perception, resilience is not just about minimizing and managing the impact of natural disasters. It is about creating the agility needed to adapt to unexpected challenges—whatever they may be —and the capacity to seize opportunity from adversity. This analysis of seven principles of resiliency includes practical suggestions for implementing each one, along with examples of companies that have managed to improve their operational effectiveness, even in time of crisis, by putting these precepts into practice. ©2015 Wiley Periodicals, Inc.
The Leader's Role in Managing Change: Five Cases of Technology‐Enabled Business Transformation
Authors: Kumar Basu Kallol
Published: February 2015

Transformation is critical for any organization to succeed, and technology‐enabled change has become a widespread means of improving responsiveness to competition and customer satisfaction. In the current climate of economic uncertainty, the imperatives that are instrumental in pushing organizations to consider transformation include innovation, business agility to adapt to external changes efficiently and effectively, the alignment of information technology (IT) and business strategy, and global demand and support for new ideas and new opportunities. The critical success factor for such initiatives lies in effective leadership to manage the changes associated with both people and processes. A review of the various aspects of leadership and change management and an analysis of five case studies in technology transformation identify the common leadership parameters that can lead to the effective and efficient adoption of change. ©2015 Wiley Periodicals, Inc.
Achieving Contextual Ambidexterity With Communities of Practice at GDF SUEZ
Authors: Barlatier Pierre‐Jean , Dupouët Olivier
Published: February 2015

Exploring paths for new business while exploiting current opportunities is a difficult task to fulfill, as it may make conflicting demands on organizational resources. Ambidextrous firms are able to achieve this goal by either splitting their resources between the two tasks or by allowing sufficient flexibility for employees to move between them within a network of communities of practice (CoPs). An analysis of the experiences of GDF SUEZ, a French multinational firm, show that CoPs at the business unit level serve as platforms from which knowledge is produced and broadcast to the rest of the organization and provide an environment in which individuals are able to move freely between exploration and exploitation activities. The study also offers practical guidance on how managers can best capture and leverage the knowledge that is generated through such collaborative endeavors. ©2015 Wiley Periodicals, Inc.
The meta‐analytic big bang
Authors: Shadish William R. , Lecy Jesse D.
Published: February 2015

This article looks at the impact of meta‐analysis and then explores why meta‐analysis was developed at the time and by the scholars it did in the social sciences in the 1970s. For the first problem, impact, it examines the impact of meta‐analysis using citation network analysis. The impact is seen in the sciences, arts and humanities, and on such contemporaneous developments as multilevel modeling, medical statistics, qualitative methods, program evaluation, and single‐case design. Using a constrained snowball sample of citations, we highlight key articles that are either most highly cited or most central to the systematic review network. Then, the article examines why meta‐analysis came to be in the 1970s in the social sciences through the work of Gene Glass, Robert Rosenthal, and Frank Schmidt, each of whom developed similar theories of meta‐analysis at about the same time. The article ends by explaining how Simonton's chance configuration theory and Campbell's evolutionary epistemology can illuminate why meta‐analysis occurred with these scholars when it did and not in medical sciences. Copyright © 2015 John Wiley & Sons, Ltd.
Surgeon‐performed ultrasound‐guided FNAC with on‐site cytopathology improves adequacy and accuracy
Authors: Witt Robert L. , Sukumar V. Raman , Gerges Fady
Published: February 2015

Objective

To demonstrate that surgeon‐performed fine‐needle aspiration cytology (FNAC) results in a high percent of satisfactory FNAC results; the number of passes to obtain a satisfactory cytological result with on‐site cytopathological interpretation is reduced with ultrasound guidance (comparing FNAC with and without surgeon‐performed ultrasound guidance); and immediate triage for indeterminate thyroid nodules can be performed in one setting for molecular testing, potentially improving selection for surgery.

Study Design

Retrospective cohort comparison.

Methods

A cytopathologist is present for on‐site staining adequacy evaluation and molecular testing triage for indeterminate cytology. Overall cytological adequacy and number of passes required to obtain cytological adequacy for 200 consecutive patients are compared with a historical series of 100 consecutive patients from the same surgeon and cytopathologists without ultrasound guidance.

Results

The percent of patients with an adequate FNAC with ultrasound guidance was 100%. The mean number of passes with and without ultrasound guidance was 1.7 and 4.0 (P < 0.001). Indeterminate FNACs (9%) were triaged to molecular alteration testing and gene expression classifier testing.

Conclusions

Surgeon‐performed ultrasound‐guided FNAC with an experienced cytopathologist present resulted in a cytologically adequate result in 100% of cases. Significantly fewer passes for a satisfactory result were achieved with ultrasound guidance. Indeterminate FNAC can be triaged for molecular testing in one patient visit, was required in only 9% of carefully selected patients, and improved patient selection for surgery. The percent of patients who went on to surgery was 24 of 200 (12%). The percent of patients who had malignancy was 18 of 24 (75%).

Level of Evidence

4. Laryngoscope, 125:1633–1636, 2015
Inclusion Complexes Between Polytetrahydrofuran‐b‐Amylose Block Copolymers and Polytetrahydrofuran Chains
Authors: Rachmawati Rachmawati , Woortman Albert J. J. , Kumar Kamlesh , Loos Katja
Published: February 2015

Amylose inclusion complexes are prepared by complexation of synthetic amylose having a covalently attached PTHF block (PTHF‐b‐amylose) with guest polytetrahydrofuran of molecular weights of 650 and 1000 g · mol−1 (PTHF650 and PTHF1000). Differential Scanning Calorimetry (DSC) analysis of the products shows a characteristic melting peak of the complexes at 140 °C. Compared to PTHF650, the PTHF1000 displays lower complexing ability with PTHF‐b‐amylose which is indicated by visible amylose retrogradation. The possible structures of the resulting products are estimated from Thermo Gravimetric Analysis (TGA) which reveals differences between PTHF‐b‐amylose and the corresponding complexes. In addition, X‐Ray Diffraction (XRD) analysis demonstrates that the resulting structures of the complexes consist of 6‐fold V‐amylose helices. The results are confirmed further with Small Angle X‐Ray Scattering (SAXS) diffractions which show that formation of inclusion complexes increases the crystalline size and regularity of the complex. There is a strong indication that the covalently attached PTHF block also induces the formation of V‐amylose by residing in between the amylose blocks. In this case, the resulting structure of the complex is likely affected by both the complexation between amylose block and the added PTHF and by the in situ self‐assembly of the block copolymers.
Self‐assembled UCST‐Type Micelles as Potential Drug Carriers for Cancer Therapeutics
Authors: Huang Gang , Li Hao , Feng Shi‐Ting , Li Xiaoqiong , Tong Guoquan , Liu Jie , Quan Changyun , Jiang Qing , Zhang Chao , Li Ziping
Published: February 2015

A methoxy‐poly(ethylene glycol)‐block‐poly(acrylamide‐co‐acrylonitrile) (mPEG‐b‐P(AAm‐co‐AN)) amphiphilic copolymer exhibiting upper critical solution temperature (UCST) behavior is synthesized, and micelles from this copolymer are fabricated. It is found that the thermal responses of these micelles are tunable through balancing the hydrophobic/hydrophilic blocks in the copolymer. The size of the doxorubicin (DOX)‐loaded micelles is dependent on the hydrophobic interaction as well as hydrogen bonding between polymer and drug molecules. As a proof of concept, the drug release behavior is studied in vitro, and the cumulative release of DOX increases at temperature above the UCST of blank micelles. 3‐(4,5‐dimethyl‐thiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assays indicate that these polymers are non‐toxic towards human hepatic carcinoma cells (Bel 7402 cells) as well as human embryonic hepatocytes (L02 cells). DOX‐loaded micelles could effectively enter Bel 7402 cells in 2 h, and display much lower half inhibitory concentration compared with free DOX. These micelles may be exploited as a promising drug carrier for cancer therapeutics.

image
Root‐flipped multiband refocusing pulses
Authors: Sharma Anuj , Lustig Michael , Grissom William A
Published: February 2015

Purpose

To design low peak power multiband refocusing radiofrequency pulses, with application to simultaneous multislice spin echo MRI.

Theory and Methods

Multiband Shinnar–Le Roux β polynomials were designed using convex optimization. A Monte Carlo algorithm was used to determine patterns of β polynomial root flips that minimized the peak power of the resulting refocusing pulses. Phase‐matched multiband excitation pulses were also designed to obtain linear‐phase spin echoes. Simulations compared the performance of the root‐flipped pulses with time‐shifted and phase‐optimized pulses. Phantom and in vivo experiments at 7T validated the function of the root‐flipped pulses and compared them to time‐shifted spin echo signal profiles.

Results

Averaged across number of slices, time‐bandwidth product, and slice separation, the root‐flipped pulses have 46% shorter durations than time‐shifted pulses with the same peak radiofrequency amplitude. Unlike time‐shifted and phase‐optimized pulses, the root‐flipped pulses' excitation errors do not increase with decreasing band separation. Experiments showed that the root‐flipped pulses excited the desired slices at the target locations, and that for equivalent slice characteristics, the shorter root‐flipped pulses allowed shorter echo times, resulting in higher signal than time‐shifted pulses.

Conclusion

The proposed root‐flipped multiband radiofrequency pulse design method produces low peak power pulses for simultaneous multislice spin echo MRI. Magn Reson Med 75:227–237, 2016. © 2015 Wiley Periodicals, Inc.
Muscle pathology grade for facioscapulohumeral muscular dystrophy biopsies
Authors: Statland Jeffrey M. , Shah Bharati , Henderson Don , Van Der Maarel Silvere , Tapscott Stephen J. , Tawil Rabi
Published: February 2015

Introduction: As we move toward planning for clinical trials in facioscapulohumeral muscular dystrophy (FSHD), a better understanding of the clinical relationship with morphological changes in FSHD muscle biopsies will be important for stratifying patients and understanding post‐therapeutic changes in muscle. Methods: We performed a prospective cross‐sectional study of quadriceps muscle biopsies in 74 genetically confirmed FSHD participants (64 with FSHD type 1 and 10 with FSHD type 2). We compared a 12‐point muscle pathology grade to genetic mutation, disease severity score, and quantitative myometry. Results: Pathology grade had moderate correlations with genetic mutation (rho = –0.45, P < 0.001), clinical severity score (rho = 0.53, P < 0.001), disease duration (rho = 0.31, P = 0.03), and quantitative myometry (rho = –0.47, P < 0.001). We found no difference in the frequency of inflammation between FSHD types 1 and 2. Conclusions: The pathology grade of quadriceps muscle may be a useful marker of disease activity in FSHD, and it may have a role in stratification for future clinical trials. Muscle Nerve 52: 521–526, 2015
W(h)ither human cardiac and body magnetic resonance at ultrahigh fields? technical advances, practical considerations, applications, and clinical opportunities
Authors: Niendorf Thoralf , Paul Katharina , Oezerdem Celal , Graessl Andreas , Klix Sabrina , Huelnhagen Till , Hezel Fabian , Rieger Jan , Waiczies Helmar , Frahm Jens , Nagel Armin M. , Oberacker Eva , Winter Lukas
Published: February 2015

The objective of this study was to document and review advances and groundbreaking progress in cardiac and body MR at ultrahigh fields (UHF,B0≥ 7.0 T) with the goal to attract talent, clinical adopters, collaborations and resources to the biomedical and diagnostic imaging communities.

This review surveys traits, advantages and challenges of cardiac and body MR at 7.0 T. The considerations run the gamut from technical advances to clinical opportunities. Key concepts, emerging technologies, practical considerations, frontier applications and future directions of UHF body and cardiac MR are provided. Examples of UHF cardiac and body imaging strategies are demonstrated. Their added value over the kindred counterparts at lower fields is explored along with an outline of research promises.

The achievements of cardiac and body UHF‐MR are powerful motivators and enablers, since extra speed, signal and imaging capabilities may be invested to overcome the fundamental constraints that continue to hamper traditional cardiac and body MR applications.

If practical obstacles, concomitant physics effects and technical impediments can be overcome in equal measure, sophisticated cardiac and body UHF‐MR will help to open the door to new MRI and MRS approaches for basic research and clinical science, with the lessons learned at 7.0 T being transferred into broad clinical use including diagnostics and therapy guiding at lower fields. Copyright © 2015 John Wiley & Sons, Ltd.
The complexity of integrating passenger routing decisions in public transportation models
Authors: Schmidt Marie , Schöbel Anita
Published: February 2015

To model and solve optimization problems arising in public transportation, data about the passengers are necessary and have to be included in the models in any phase of the planning process. Many approaches assume a two‐step procedure: in a first step, the data about the passengers are distributed over the public transportation network (PTN) using traffic‐assignment procedures. In a second step, the actual planning of lines, timetables, and so forth takes place. This approach ignores that, assuming that the network is sufficiently dense, for most passengers, there are many possible ways to reach their destinations in the PTN, thus the actual connections the passengers will take strongly depend on the decisions made during the planning phase. In this article, we investigate the influence of integrating the traffic assignment procedure in the optimization process on the complexity of the line planning problem. Our objective is to maximize the passengers' benefit, namely to minimize the overall travel time of the passengers in the network. We present new models and systematically analyze their complexities. Exploiting a relation to the resource‐constrained shortest path problem, we are able to derive pseudopolynomial and polynomial algorithms for special cases. © 2015 Wiley Periodicals, Inc. NETWORKS, Vol. 65(3), 228–243 2015