bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relaxin: New Pathophysiological Aspects and Pharmacological Perspectives for an Old Protein
Authors: Cernaro Valeria , Lacquaniti Antonio , Lupica Rosaria , Buemi Antoine , Trimboli Domenico , Giorgianni Grazia , Bolignano Davide , Buemi Michele 
Published: February 2013

AbstractHuman relaxin‐2 (hereafter simply defined as “relaxin”) is a 6‐kDa peptidic hormone best known for the physiological role played during pregnancy in the growth and differentiation of the reproductive tract and in the renal and systemic hemodynamic changes. This factor can also be involved in the pathophysiology of arterial hypertension and heart failure, in the molecular pathways of fibrosis and cancer, and in angiogenesis and bone remodeling. It belongs to the relaxin peptide family, whose members comprehensively exert numerous effects through interaction with different types of receptors, classified as relaxin family peptide (RXFP) receptors (RXFP1, RXFP2, RXFP3, RXFP4). Research looks toward the in‐depth examination and complete understanding of relaxin in its various pleiotropic actions. The intent is to evaluate the likelihood of employing this substance for therapeutic purposes, for instance in diseases where a deficit could be part of the underlying pathophysiological mechanisms, also avoiding any adverse effect. Relaxin is already being considered as a promising drug, especially in acute heart failure. A careful study of the different RXFPs and their receptors and the comprehension of all biological activities of these hormones will probably provide new drugs with a potential wide range of therapeutic applications in the near future.
Accelerated fractional ventilation imaging with hyperpolarized Gas MRI
Authors: Emami Kiarash , Xu Yinan , Hamedani Hooman , Profka Harrilla , Kadlecek Stephen , Xin Yi , Ishii Masaru , Rizi Rahim R. 
Published: February 2013

PurposeTo investigate the utility of accelerated imaging to enhance multibreath fractional ventilation (r) measurement accuracy using hyperpolarized gas MRI. Undersampling shortens the breath‐hold time, thereby reducing the O2‐induced signal decay and allows subjects to maintain a more physiologically relevant breathing pattern. Additionally, it may improve r estimation accuracy by reducing radiofrequency destruction of hyperpolarized gas.MethodsImage acceleration was achieved using an eight‐channel phased array coil. Undersampled image acquisition was simulated in a series of ventilation images and data was reconstructed for various matrix sizes (48–128) using generalized auto‐calibrating partially parallel acquisition. Parallel accelerated r imaging was also performed on five mechanically ventilated pigs.ResultsOptimal acceleration factor was fairly invariable (2.0–2.2×) over the range of simulated resolutions. Estimation accuracy progressively improved with higher resolutions (39–51% error reduction). In vivo r values were not significantly different between the two methods: 0.27 ± 0.09, 0.35 ± 0.06, 0.40 ± 0.04 (standard) versus 0.23 ± 0.05, 0.34 ± 0.03, 0.37 ± 0.02 (accelerated); for anterior, medial, and posterior slices, respectively, whereas the corresponding vertical r gradients were significant (P < 0.001): 0.021 ± 0.007 (standard) versus 0.019 ± 0.005 (accelerated) (cm−1).ConclusionQuadruple phased array coil simulations resulted in an optimal acceleration factor of ∼2× independent of imaging resolution. Results advocate undersampled image acceleration to improve accuracy of fractional ventilation measurement with hyperpolarized gas MRI. Magn Reson Med 70:1353–1359, 2013. © 2013 Wiley Periodicals, Inc.
Improved slice‐selective adiabatic excitation
Authors: Balchandani Priti , Glover Gary , Pauly John , Spielman Daniel 
Published: February 2013

PurposeThe purpose of this work is to design an improved Slice‐selective Tunable‐flip AdiaBatic Low peak‐power Excitation (STABLE) pulse with shorter duration and increased off‐resonance immunity to make it suitable for use in a greater range of applications and at higher field strengths. An additional aim is to design a variant of this pulse to achieve B1‐insensitive, fat‐suppressed excitation.MethodsThe adiabatic SLR algorithm was used to generate a more uniform spectral pulse envelope for this improved radiofrequency pulse for adiabatic slice‐selective excitation, called STABLE‐2. Pulse parameters were adjusted to design a version of STABLE‐2 with a spectral null centered on lipids.ResultsIn vivo images obtained of the human brain at 3 and 7 T demonstrate that STABLE‐2 provides robust, uniform, slice‐selective excitation over a range of B1 values. Phantom and in vivo knee images obtained at 3 T demonstrate the effectiveness of STABLE‐2 for fat suppression.ConclusionsSTABLE‐2 achieves B1‐insensitive slice‐selective excitation while providing greater off‐resonance immunity and a shorter pulse duration, when compared to the original STABLE pulse. In particular, the 9.8‐ms STABLE‐2 pulse provides slice selectivity over 120 Hz whereas the 21‐ms STABLE pulse is limited to 80 Hz off‐resonance. B1‐Insensitive fat‐suppressed excitation may also be achieved by using a variant of this pulse. Magn Reson Med 71:75–82, 2014. © 2013 Wiley Periodicals, Inc.
High‐resolution, large dynamic range field map estimation
Authors: Dagher Joseph , Reese Timothy , Bilgin Ali 
Published: February 2013

PurposeWe present a theory and a corresponding method to compute high‐resolution field maps over a large dynamic range.Theory and MethodsWe derive a closed‐form expression for the error in the field map value when computed from two echoes. We formulate an optimization problem to choose three echo times which result in a pair of maximally distinct error distributions. We use standard field mapping sequences at the prescribed echo times. We then design a corresponding estimation algorithm which takes advantage of the optimized echo times to disambiguate the field offset value.ResultsWe validate our method using high‐resolution images of a phantom at 7T. The resulting field maps demonstrate robust mapping over both a large dynamic range, and in low SNR regions. We also present high‐resolution offset maps in vivo using both, GRE and multiecho gradient echo sequences. Even though the proposed echo time spacings are larger than the well known phase aliasing cutoff, the resulting field maps exhibit a large dynamic range without the use of phase unwrapping or spatial regularization techniques.ConclusionWe demonstrate a novel three‐echo field map estimation method which overcomes the traditional noise‐dynamic range trade‐off. Magn Reson Med 71:105–117, 2014. © 2013 Wiley Periodicals, Inc.
Sensitivity and Source of Amine‐Proton Exchange and Amide‐Proton Transfer Magnetic Resonance Imaging in Cerebral Ischemia
Authors: Zong Xiaopeng , Wang Ping , Kim Seong‐Gi , Jin Tao 
Published: February 2013

PurposeAmide‐proton transfer (APT) and amine–water proton exchange (APEX) MRI can be viable to map pH‐decreasing ischemic regions. However, their exact contributions are unclear.MethodsWe measured APEX‐ and APT‐weighted magnetization transfer ratio asymmetry (denoted as APEXw and APTw), apparent diffusion coefficient, T2, and T1 images and localized proton spectra in rats with permanent middle cerebral artery occlusion at 9.4 T. Phantoms and theoretical studies were also performed.ResultsWithin 1‐h postocclusion, APEXw and APTw maps showed hyperintensity (3.1% of M0) and hypointensity (−1.8%), respectively, in regions with decreased apparent diffusion coefficient. Ischemia increased lactate and gamma aminobutyric acid concentrations, but decreased glutamate and taurine concentrations. Over time, the APEXw contrast decreased with glutamate, taurine, and creatine, whereas the APTw contrast and lactate level were similar. Phantom and theoretical studies suggest that the source of APEXw signal is mainly from proteins at normal pH, whereas at decreased pH, gamma aminobutyric acid and glutamate contributions increase, inducing the positive APEXw contrast in ischemic regions. The APTw contrast is sensitive to lactate concentration and pH, but contaminated from contributions of the faster APEX processes.ConclusionPositive APEXw contrast is more sensitive to ischemia than negative APTw contrast. They may provide complementary tissue metabolic information. Magn Reson Med 71:118–132, 2014. © 2013 Wiley Periodicals, Inc.
Imaging of Endogenous Exchangeable Proton Signals in the Human Brain Using Frequency Labeled Exchange Transfer Imaging
Authors: Yadav Nirbhay N. , Jones Craig K. , Hua Jun , Xu Jiadi , van Zijl Peter C. M. 
Published: February 2013

PurposeTo image endogenous exchangeable proton signals in the human brain using a recently reported method called frequency labeled exchange transfer (FLEX) MRI.MethodsAs opposed to labeling exchangeable protons using saturation (i.e., chemical exchange saturation transfer, or CEST), FLEX labels exchangeable protons with their chemical shift evolution. The use of short high‐power frequency pulses allows more efficient labeling of rapidly exchanging protons, while time domain acquisition allows removal of contamination from semi‐solid magnetization transfer effects.ResultsFLEX‐based exchangeable proton signals were detected in human brain over the 1–5 ppm frequency range from water. Conventional magnetization transfer contrast and the bulk water signal did not interfere in the FLEX spectrum. The information content of these signals differed from in vivo CEST data in that the average exchange rate of these signals was 350–400 s−1, much faster than the amide signal usually detected using direct saturation (∼30 s−1). Similarly, fast exchanging protons could be detected in egg white in the same frequency range where amide and amine protons of mobile proteins and peptides are known to resonate.ConclusionsFLEX MRI in the human brain preferentially detects more rapidly exchanging amide/amine protons compared to traditional CEST experiments, thereby changing the information content of the exchangeable proton spectrum. This has the potential to open up different types of endogenous applications as well as more easy detection of rapidly exchanging protons in diaCEST agents or fast exchanging units such as water molecules in paracest agents without interference of conventional magnetization transfer contrast. Magn Reson Med 69:966–973, 2013. © 2013 Wiley Periodicals, Inc.
Post‐mortem apparent resolution of fetal ventriculomegaly: evidence from magnetic resonance imaging
Authors: Sebire Neil J. , Miller Sarah , Jacques Thomas S. , Taylor Andrew M. , Rennie Janet M. , Kendall Giles , Chitty Lyn S. 
Published: February 2013

ABSTRACTObjectiveThis study aims to determine the accuracy of post‐mortem magnetic resonance imaging (MRI) and autopsy for confirmation of sonographically detected fetal ventriculomegaly.MethodsThis study uses retrospective review of fetuses with sonographically diagnosed ventriculomegaly, where the pregnancy was terminated and post‐mortem examination was performed during a period in which post‐mortem MRI was being offered.ResultsSixteen cases were identified. In nine (56%), autopsy and/or post‐mortem MRI confirmed the prenatal findings. In the other seven, both autopsy and post‐mortem MRI demonstrated no ventriculomegaly, but antenatal MRI confirmed the ultrasound findings in 6/7 cases where it had been performed. Post‐mortem investigations confirmed antenatal findings in 8/9 cases with severe ventriculomegaly (posterior horn measurement >15 mm), whereas only 2/7 in which ventriculomegaly was not confirmed had severe ventriculomegaly.ConclusionsPost‐mortem examination, both by traditional neuropathological examination, and post‐mortem MRI may fail to confirm prenatal ventriculomegaly in around half of cases. The post‐mortem MRI findings indicate that this is due to resolution of ventriculomegaly rather than autopsy artefact, and is presumably a consequence of post‐mortem fluid redistribution. Parents should be advised before termination of pregnancy that post‐mortem confirmation of ventriculomegaly, especially in mild cases, may not be possible. Antenatal MRI may be a better approach for confirming prenatal ultrasound findings. © 2013 John Wiley & Sons, Ltd.
Pharmacokinetics of Intravenous Voriconazole in Obese Patients: Implications of CYP2C19 Homozygous Poor Metabolizer Genotype
Authors: Moriyama Brad , Jarosinski Paul F. , Figg William D. , Henning Stacey A. , Danner Robert L. , Penzak Scott R. , Wayne Alan S. , Walsh Thomas J. 
Published: February 2013

There is a paucity of pharmacokinetic studies describing weight‐based dosing of intravenous voriconazole in obese patients. In this case report, we describe the pharmacokinetics of intravenous voriconazole in an obese CYP2C19 homozygous poor metabolizer and review previously reported data regarding the use of intravenous voriconazole in obese patients. A 17‐year‐old obese Hispanic male patient (body mass index 35 kg/m2) received intravenous voriconazole for the treatment of suspected aspergillosis. After 2.5 days of voriconazole 4 mg/kg intravenously every 12 hours based on adjusted body weight, the voriconazole area under the serum concentration–time curve over the course of a single (12‐hr) dosing interval and trough concentration were 86,100 ng · hr/ml and 6.2 µg/ml, respectively. Six days later, the voriconazole dosage was decreased. A trough concentration measured just before the dosage reduction (after 8.5 days of voriconazole 4 mg/kg intravenously every 12 hours based on adjusted body weight) remained elevated at 5.8 µg/ml. Genotyping revealed a CYP2C19 homozygous poor metabolizer (CYP2C19*2/*2). Voriconazole was subsequently discontinued due to QTc prolongation. These data and those from two recent publications suggest that voriconazole does not distribute extensively into human adipose tissue and that obese patients should be dosed on an adjusted body weight basis. If an obese patient dosed on total body weight is also a CYP2C19 poor metabolizer, serum voriconazole concentrations will be further elevated, potentially leading to drug‐induced toxicity.
Rash Associated with Dabigatran Etexilate
Authors: To Kim , Reynolds Carl , Spinler Sarah A. 
Published: February 2013

Patients experiencing atrial fibrillation are at an increased risk for thromboembolic events. Therefore, anticoagulation therapy is imperative to prevent thrombus formation and stroke. Dabigatran etexilate was approved by the Food and Drug Administration in 2010 as anticoagulant prophylaxis for patients with nonvalvular atrial fibrillation. The frequency of dermatologic reactions to dabigatran etexilate is estimated in the product labeling to be less than 0.1%. To date, five cases of dabigatran etexilate–associated rash have reported, including three published cases. We describe the sixth reported case of dabigatran etexilate–associated rash, in a 59‐year‐old man with a history of atrial fibrillation who received dabigatran etexilate 150 mg twice/day for atrial flutter before cardioversion. The patient had taken dabigatran etexilate for 5 days before the rash was noted on hospital admission. He had no known previous drug allergies, and his platelet count, serum creatinine concentration, and hepatic function were normal. The rash resolved 7 days after the discontinuation of dabigatran etexilate, and the patient was stabilized on warfarin therapy. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 5) between the patient's development of the rash and dabigatran etexilate therapy. Clinicians should be aware of this adverse effect of dabigatran etexilate and monitor for dermatologic reactions during follow‐up visits.
Desired Professional Development Pathways for Clinical Pharmacists
Authors:   American College of Clinical Pharmacy, Shord Stacy S. , Schwinghammer Terry L. , Badowski Melissa , Banderas Julie , Burton Michael E. , Chapleau Christopher A. , Gallagher Jason C. , Matsuura Gregory , Parli Sara E. , Yunker Nancy 
Published: February 2013

The 2012 American College of Clinical Pharmacy (ACCP) Certification Affairs Committee was charged with developing guidelines for the desired professional development pathways for clinical pharmacists. This document summarizes recommendations for postgraduate education and training for graduates of U.S. schools and colleges of pharmacy and describes the preferred pathways for achieving, demonstrating, and maintaining competence as clinical pharmacists. After initial licensure within the state or jurisdiction in which the pharmacist intends to practice, completion of an accredited PGY1 pharmacy residency is recommended to further develop the knowledge and skills needed to optimize medication therapy outcomes. An accredited PGY2 pharmacy residency should be completed if a pharmacist wishes to seek employment in a specific therapeutic area or practice setting, if such a residency exists. Clinical pharmacists intending to conduct advanced research that is competitive for federal funding are encouraged to complete a fellowship or graduate education. Initial certification by the Board of Pharmacy Specialties (BPS) or other appropriate sponsoring organizations should be completed in the desired primary therapeutic area or practice setting within 2 years after accepting a position within the desired specific therapeutic area or practice setting. Clinical pharmacists subsequently will need to meet the requirements to maintain pharmacist licensure and board certification. Traineeships, practice‐based activities, and certificate programs can be used to obtain additional knowledge and skills that support professional growth. Pharmacists are strongly encouraged to adopt a lifelong, systematic process for professional development and work with ACCP and other professional organizations to facilitate the development and implementation of innovative strategies to assess core practice competencies.
Integrative network analysis of signaling in human CD34+ hematopoietic progenitor cells by global phosphoproteomic profiling using TiO2 enrichment combined with 2D LC‐MS/MS and pathway mapping
Authors: Guo Hongbo , Isserlin Ruth , Chen Xiaoji , Wang Weijia , Phanse Sadhna , Zandstra Peter W. , Paddison Patrick J. , Emili Andrew 
Published: February 2013

Protein kinase signaling regulates human hematopoietic stem/progenitor cell (HSPC) fate, yet little is known about critical pathway substrates. To address this, we have developed and applied a large‐scale, empirically optimized phosphopeptide affinity enrichment strategy with high‐throughput 2D LC‐MS/MS screening to evaluate the phosphoproteome of an isolated human CD34+ HSPC population. We first used hydrophilic interaction chromatography as a first dimension separation to separate and simplify protein digest mixtures into discrete fractions. Phosphopeptides were then enriched off‐line using TiO2‐coated magnetic beads and subsequently detected online by C18 RP nanoflow HPLC using data‐dependent MS/MS high‐energy collision‐activated dissociation fragmentation on a high‐performance Orbitrap hybrid tandem mass spectrometer. We identified 15 533 unique phosphopeptides in 3574 putative phosphoproteins. Systematic computational analysis revealed biological pathways and phosphopeptide motifs enriched in CD34+ HSPC that are markedly different from those observed in an analogous parallel analysis of isolated human T cells, pointing to the possible involvement of specific kinase‐substrate relationships within activated cascades driving hematopoietic renewal, commitment, and differentiation.
Plasma glucose monitoring in psychiatric inpatients with primary affective disorder
Authors: Kelbrick Marlene , Picchioni Marco 
Published: February 2013

AbstractPeople with affective disorders are at increased risk of diabetes mellitus; however, glucose monitoring practices vary widely in mental health settings across the UK. Here, Drs Kelbrick and Picchioni describe their audit to identify patients with a primary affective disorder and co‐morbid diabetes admitted to a Northamptonshire acute inpatient unit and to establish the level of compliance with local and national guidelines regarding plasma glucose and diabetes monitoring.
Is autoimmunity involved in the aetiology of schizophrenia?
Authors: Pandarakalam James Paul 
Published: February 2013

AbstractA century of research into the aetiology of schizophrenia has not been substantially productive. However, in recent years, there has been a resurgence of interest in a possible autoimmune involvement in a subset of patients with schizophrenia. Here, Dr Pandarakalam discusses the evidence.
Investigation on Ultraviolet Absorption Properties, Migration, and Catalytic Performances of Ferrocene‐Modified Hyper‐Branched Polyesters
Authors: Xiao Fengjuan , Feng Feifei , Li Lanlan , Zhang Dan 
Published: February 2013

AbstractThe ultraviolet absorption properties of a series of ferrocene‐modified hyper‐branched polyesters (HBPE‐Fcs) were analyzed by Ultraviolet/visible spectrometry. HBPE‐Fcs were used as burning rate catalyst components added into hydroxyl‐terminated polybutadiene (HTPB) based elastomers to investigate their migration behavior. Migration inhibition effects of HBPE‐Fcs in different aging conditions were analyzed. The diffusion coefficients (D) of the migration components were calculated according to Fick’s law of diffusion. The catalytic performances of HBPE‐Fcs for the thermal decomposition of cyclotrimethylenetrinitramine (RDX) were also investigated by non isothermal measurements using Kissinger method. The incorporation of ferrocenes into hyper‐branched polyesters (HBPEs) endows HBPEs with new ultraviolet absorption properties. The migration of HBPE‐Fc was minimized by grafting ferrocene on the hyper‐branched structures compared to that of simple ferrocene derivatives. HBPE‐Fcs present efficient catalytic effects on the thermal degradation of RDX; and, the catalytic reactions were characterized by decreased activation energies and increased rate constants.
Energetically unfavorable amide conformations for N6‐acetyllysine side chains in refined protein structures
Authors: Genshaft Alexander , Moser Joe‐Ann S. , D'Antonio Edward L. , Bowman Christine M. , Christianson David W. 
Published: February 2013

AbstractThe reversible acetylation of lysine to form N6‐acetyllysine in the regulation of protein function is a hallmark of epigenetics. Acetylation of the positively charged amino group of the lysine side chain generates a neutral N‐alkylacetamide moiety that serves as a molecular “switch” for the modulation of protein function and protein–protein interactions. We now report the analysis of 381 N6‐acetyllysine side chain amide conformations as found in 79 protein crystal structures and 11 protein NMR structures deposited in the Protein Data Bank (PDB) of the Research Collaboratory for Structural Bioinformatics. We find that only 74.3% of N6‐acetyllysine residues in protein crystal structures and 46.5% in protein NMR structures contain amide groups with energetically preferred trans or generously trans conformations. Surprisingly, 17.6% of N6‐acetyllysine residues in protein crystal structures and 5.3% in protein NMR structures contain amide groups with energetically unfavorable cis or generously cis conformations. Even more surprisingly, 8.1% of N6‐acetyllysine residues in protein crystal structures and 48.2% in NMR structures contain amide groups with energetically prohibitive twisted conformations that approach the transition state structure for cis‐trans isomerization. In contrast, 109 unique N‐alkylacetamide groups contained in 84 highly accurate small molecule crystal structures retrieved from the Cambridge Structural Database exclusively adopt energetically preferred trans conformations. Therefore, we conclude that cis and twisted N6‐acetyllysine amides in protein structures deposited in the PDB are erroneously modeled due to their energetically unfavorable or prohibitive conformations. Proteins 2013; © 2012 Wiley Periodicals, Inc.