bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversible Covalent and Supramolecular Functionalization of Water‐Soluble Gold(I) Complexes
Authors: Kemper Benedict , von Gröning Maximilian , Lewe Vanessa , Spitzer Daniel , Otremba Tobias , Stergiou Natascha , Schollmeyer Dieter , Schmitt Edgar , Ravoo Bart Jan , Besenius Pol
Published: February 2017

The ligation of gold(I) metalloamphiphiles with biomolecules is reported, using water‐soluble AuI‐N‐alkynyl substituted maleimide complexes. For this purpose, two different polar ligands were applied: 1) a neutral, dendritic tetraethylene glycol‐functionalized phosphane and 2) a charged, sulfonated N‐heterocyclic carbene (NHC). The retro Diels–Alder reaction of a furan‐protected maleimide gold(I) complex, followed by cycloaddition with a diene‐functionalized biotin under mild conditions leads to a novel gold(I) metalloamphiphile. The strong streptavidin–biotin binding affinity in buffered aqueous solution of the resulting biotin alkynyl gold(I) phosphane conjugate remains intact. The cytotoxicity of the biotinylated gold(I) complex against a T47D human breast cancer cell line is higher than for cisplatin.
Determinants of the recommended phase 2 dose of molecular targeted agents
Authors: Hansen Aaron R. , Cook Natalie , Amir Eitan , Siu Lillian L. , Abdul Razak Albiruni Ryan
Published: February 2017

BACKGROUND

The recommended phase 2 dose (RP2D) of anticancer agents is determined traditionally by dose‐limiting toxicities. Nontoxicity or biological endpoints such as pharmacokinetics, pharmacodynamics, and efficacy can also be used to identify RP2D, which may be relevant to molecularly targeted agents (MTAs).

METHODS

A systematic review identified all monotherapy phase 1 studies of MTAs in solid tumors published between 2001 and 2013. Dose, dosing schedule, and determinants of RP2D were collected from each study. A supplementary search of the US Food and Drug Administration (FDA) website identified the licensed dose for drugs with regulatory approval. Logistic regression was used to explore predictors for the RP2D being consistent with the final approved dose.

RESULTS

The search identified 4175 records, of which 250 studies evaluating 181 individual MTAs were included. Of these MTAs, 161 (64%) determined an RP2D. Fifty‐two trials (32%), used toxicity alone to specify an RP2D. The remaining trials used a nonclassical approach with either multiple endpoints that included toxicity (n = 87, 54%), multiple nontoxicity endpoints (n = 12, 7%), or a single nontoxicity endpoint (n = 10, 6%). Twenty‐nine (16%) MTAs were approved by the FDA for solid tumor indications. The use of nonclassical definitions compared with toxicity alone was significantly associated with higher likelihood of FDA approval (odds ratio, 5.03; 95% confidence interval, 1.11‐22.73; P = .036).

CONCLUSIONS

In the past decade, there has been a dominance of a nonclassical approach using multiple endpoints with or without toxicity or single nontoxicity endpoints to define RPTD in MTA monotherapy phase 1 trials. Nonclassically defined RP2Ds for MTAs appear to be associated with a higher rate of FDA drug approval. Cancer 2017;123:1409–1415. © 2016 American Cancer Society.
Words matter: Restoring respect and dignity when referring to individuals with cancer
Authors: Ellis Lee M. , Blanke Charles D. , Kohn Elise C.
Published: February 2017

Respecting our patients is the first reassuring step in a long, shared journey during cancer therapy and beyond. The provision of excellent oncologic and medical care in the absence of empathy and respect undermines and compromises the potential value of any intervention.
Development and validation of a new Italian short measure of disgust propensity: The Disgust Propensity Questionnaire (DPQ)
Authors: Melli Gabriele , Chiorri Carlo , Stopani Eleonora , Bulli Francesco , Carraresi Claudia
Published: February 2017

Although a few measures of disgust propensity are available in Italy, most of them take a long time to administer and/or have not shown replicable and sound psychometric properties. In the current study, the authors developed an Italian nine‐item self‐report measure of disgust propensity (particularly of pathogen disgust)—the Disgust Propensity Questionnaire (DPQ)—to address the limitations of currently available measures. In Study 1, the DPQ was developed through exploratory and confirmatory factor analyses from an initial pool of 33 items that were administered to 784 nonclinical participants. The DPQ showed evidence of an adequate factorial and construct validity as well as internal consistency and temporal stability. In Study 2, additional evidence of the sound psychometric properties of the DPQ was provided by analyzing an independent sample of 315 nonclinical participants and a sample of 208 patients with obsessive–compulsive disorder. This study also showed that the DPQ can discriminate between obsessive–compulsive disorder patients with and without contamination‐related concerns, patients with anxiety disorders, and nonclinical participants.

Key Practitioner Message

An Italian nine‐item self‐report disgust propensity measure was developed to address the limitations of currently available tools.

The Disgust Propensity Questionnaire (DPQ) was evaluated using two independent studies in nonclinical and clinical samples.

The DPQ showed adequate factorial and construct validity, internal consistency, and temporal stability.

It could discriminate between patients with obsessive–compulsive disorder with contamination‐related concerns and all other groups.

It is a very short and psychometrically sound measure to assess disgust propensity in Italian samples.
Receiver design for multicarrier transmission systems in presence of Tx/Rx imperfections
Authors: Ali Muhammad Asim , Sandhu Muhammad Yameen , Waqar Omar , Rahimo Abdul Qadir
Published: February 2017

The aim of this article is to design a simple receiver, which can jointly estimate the frequency selective channel impulse response, frequency independent transmit/receive IQ imbalance, and carrier frequency offset with minimal training and implementation complexity. The estimation of carrier frequency offset is performed using 2 scalable solutions. To estimate the frequency selective channel impulse response and frequency independent transmit/receive IQ imbalance, we proposed 2 different estimation techniques. The first technique is an iterative approach stemming from a doubly linear model of the transmission system in the presence of transmit/receive IQ imbalance and frequency selective channel impulse response, while the second approach is a least squares solution. Both these schemes provide a good performance/complexity trade‐off. Although the iterative estimates of channel impulse response are not optimal, they do provide a near ideal bit error performance. The proposed scheme blends seamlessly with Institute of Electrical and Electronics Engineers 802.11 standard but can be adapted to work with any orthogonal frequency‐division multiplexing standard.
An exploratory study Evaluating the impact of opioid and non‐opioid pain medications on serum/plasma free testosterone and free estradiol concentrations
Authors: Ray Julie A. , Kushnir Mark M. , Meikle A. Wayne , Sindt Jill E. , Strathmann Frederick G.
Published: February 2017

Chronic use of opioid medications has been reported to cause altered sexual function. It is not known if non‐opioid pain medications have similar effects. Assessment of this effect through the measurement of concentrations of free hormones is limited. Positivity of opioid medications (hydrocodone, oxycodone, morphine, methadone, tramadol and fentanyl) and non‐opioid pain medications (gabapentin or pregabalin) in human serum and plasma samples from adult men and women were evaluated for association with concentrations of free testosterone (fTe) and free estradiol (fE2) measured using equilibrium dialysis‐liquid chromatography‐tandem mass spectrometry methods. Lower concentrations of fTe (p = 0.0253) were observed in samples positive for the hydrocodone, oxycodone and morphine group compared to age matched controls. The presence of methadone, tramadol, fentanyl and pregabalin had no effect on fTe. When compared with age‐matched controls, women between 48–55 years of age showed reduced fE2 concentrations in samples positive for tramadol, fentanyl and gabapentin (p = 0.0243, 0.0045 and 0.0050, respectively). Particular opioid medications such as methadone, tramadol or fentanyl and non‐opioid medications such as pregabalin or gabapentin may offer advantages over opioid medications for treating pain with fewer endocrinologic side effects. Measurement of free hormones in pain medication users could be important in determining their association with sexual function. Copyright © 2017 John Wiley & Sons, Ltd.
From Bis(imidazol‐2‐yl)methanes to Asymmetrically Substituted Bis(heterocyclo)methanides in Metal Coordination
Authors: Dauer David‐R. , Koehne Ingo , Herbst‐Irmer Regine , Stalke Dietmar
Published: February 2017

As an extension to the known symmetric bis(heterocyclo)methanes containing two identical heterocycles, new asymmetric ligand systems, based on benzoxazole, benzothiazole and 1‐methylbenzimidazole, are presented. Furthermore, the syntheses and reactions of two new symmetrically substituted methane derivatives, containing either 1‐methylimidazole or 1‐methylbenzimidazole, are discussed. In this context, firstly, (1‐MeNCNC2H2)2CH2 and (1‐MeNCNC6H4)2CH2, and secondly, (NCSC6H4)CH2(NCOC6H4) and (NCSC6H4)CH2(1‐MeNCNC6H4), are used as parent compounds. They can be easily deprotonated at the central methylene bridge to generate a monoanionic structure akin to NacNac, so that the following complexes can be obtained: [Me2Al{(1‐MeNCNC2H2)2CH}], [Me2Al{(1‐MeNCNC6H4)2CH}], [Me2Al{(NCSC6H4)CH(NCOC6H4)}], [Me2Ga{(NCSC6H4)CH(NCOC6H4)}], [Me2Al{(NCSC6H4)CH(1‐MeNCNC6H4)}], [(THF)2Li{(1‐MeNCNC6H4)2CH}] and [(diox)2Li{(NCSC6H4)CH(1‐MeNCNC6H4)}]. These compounds have been fully characterised by single‐crystal X‐ray diffraction (in the solid state) and NMR spectroscopy (in solution).
Stereoselective Synthesis of 1,2‐trans‐Diamines Using the Three‐Component Borono‐Mannich Condensation – Reaction Scope and Mechanistic Insights
Authors: Norsikian Stéphanie , Beretta Margaux , Cannillo Alexandre , Auvray Marie , Martin Amélie , Retailleau Pascal , Iorga Bogdan I. , Beau Jean‐Marie
Published: February 2017

The Petasis borono‐Mannich (PBM) process with easily accessible N‐protected α‐amino aldehydes produces 1,2‐trans‐diamines diastereoselectively with an enantiomeric excess up to 98 %. The protecting group on the nitrogen atom had a decisive influence on both the yield and the enantiomeric purity of the condensation products, and the best results were obtained with sulfonamide derivatives [nosyl (Ns), tosyl (Ts), and mesyl (Ms)]. To get a better understanding of the influence of the protecting group, we investigated the mechanism of the borono‐Mannich reaction through DFT calculations.
Fabrication of Photoelectrochemical Glucose Biosensor in Flow Injection Analysis System Using ZnS/CdS‐Carbon Nanotube Nanocomposite Electrode
Authors: Sağlam Özlem , Dilgin Yusuf
Published: February 2017

In this work, a photoamperometric glucose biosensor based on glucose oxidase (GODx) was developed in flow injection analysis (FIA) system using ZnS‐CdS quantum dot (QD) modified multiwalled carbon nanotube/glassy carbon electrode (ZnS‐CdS/MWCNT/GCE). Cyclic voltammograms of the proposed electrode (GODx/ZnS‐CdS/MWCNT/GCE) showed a pair of well‐defined reversible redox peak attributing that direct electron transfer between the protein and electrode. The current of the reduction peak became more cathodic in the presence of O2due to the electrocatalytic activity of the electrode towards the reduction of dissolved O2, but reduction current shifted to a less negative value upon addition of glucose in the solution. The obtained CV currents were affected by the irradiation of the electrode surface. Thus, the photoelectrochemical biosensing of glucose in the FIA system was studied by monitoring of the changes in the electrocatalyzed reduction peak current of dissolved O2at the proposed electrode dependent on glucose concentration. The proposed photoelectrochemical FIA method has a linear response to glucose ranging from of 0.01 to 1.0 mM with detection limit of 3.0 μM under optimized conditions. Photoelectrochemical biosensor was successfully fabricated in FIA system for selective, sensitive and repeatable detection of glucose and has been satisfactorily applied to determination of glucose in real sample.
Measuring Sheet Resistances of Dielectrics Using Co‐Planar Hydrogel Electrochemical Cells with Practical Applications to Characterize the Protective Quality of Paints on Sculptures
Authors: Hosbein Kathryn N. , England Alice H. , Price Capri A. , Clare Tami Lasseter
Published: February 2017

Electrical properties of thin dielectric films at the solid‐liquid phase boundary are an important performance characteristic of many devices, coatings and sensors. In this paper, co‐polymeric hydrogels of polyacrylic acid co‐sulfonic acid, swollen with a salt solution to act as the solid electrolyte, were used to assess interfaces using electrochemical impedance spectroscopy (EIS) in a co‐planar geometry. Silane‐modified glasses were characterized by the co‐planar hydrogel EIS cell and found to be distinguishable based on their surface monolayer chemistry. EIS measurements were also made on primed and painted metal substrates, using both test panels and an outdoor sculpture, Tony Smith's Stinger. The panels were then exposed to accelerated and outdoor weathering and showed degradation on the surface paint layers, which was observable electrochemically using EIS and confirmed visually by SEM. Electrochemical spectral features were compared between data from a standard paint‐test cell versus this co‐planar hydrogel cell; both cell types were able to measure coating capacitance, providing useful information about the condition of the bulk coating. Yet, sheet resistance (Rs) was a spectral feature seen only by the co‐planar hydrogel cell. Thus, it can be concluded that the use of such co‐planar hydrogel cells can provide an earlier warning sign to coating degradation and such cells provide a new type of spectral information that is not assessable by the standard geometry.
Creating a safe operating space for wetlands in a changing climate
Authors: Green Andy J , Alcorlo Paloma , Peeters Edwin THM , Morris Edward P , Espinar José L , Bravo‐Utrera Miguel Angel , Bustamante Javier , Díaz‐Delgado Ricardo , Koelmans Albert A , Mateo Rafael , Mooij Wolf M , Rodríguez‐Rodríguez Miguel , van Nes Egbert H , Scheffer Marten
Published: February 2017

Many of the world's wetlands may be profoundly affected by climate change over the coming decades. Although wetland managers may have little control over the causes of climate change, they can help to counteract its effects through local measures. This is because direct anthropogenic impacts, such as water extraction and nutrient loading, work in concert with climate change to damage wetlands. Control of these local stressors may therefore ameliorate undesired effects of climate change, such as a shift towards dominance by invasive floating plants, increasingly frequent cyanobacteria blooms, or extinction of key species. Using the iconic Doñana wetlands in Spain as a case study, we illustrate how the concept of creating a “safe operating space” may be implemented to better ensure that ecosystems do not surpass thresholds for collapse during an era of global change.
Creep behaviour and remediation concept for a deep‐seated landslide, Navistal, Tyrol, Austria
Authors: Hofmann Robert , Sausgruber Johann Thomas
Published: February 2017

In the valley of Navis, the village of Kerschbaum with 84 houses stands on a slowly downhill moving, relatively corase grained, aqua bearing earth‐flow/‐slide about 40 m thick. This secondary movement overlies a deep‐seated rock slide. The rates of movement at the surface of the earth‐flow/‐slide were between 1 und 3 cm/a before the implementation of remedial works. Starting from the geotechnical and geomechanical model of the slope, measures were developed, which were intended to reduce the movement. A monitoring system was installed to provide information about the movement and slope water conditions of the earth‐flow/‐slide and the sliding rock mass. In order to estimate the creep behaviour of the earth‐flow/‐slide, the ductility index ILZR was determined from shear tests. A simple flow law was assumed for the estimation of the change of creep rate. Measurements over a period of about 18 months after the first phase of remedial works show rates between 0.5 and 1.2 cm/a. The reduction of the rate of movement is compared with the creep model applied and the viscosity index ILZR to check the validity.
Cerebrovascular burden and depressive symptomatology interrelate over 18 years: support for the vascular depression hypothesis
Authors: Scott Rosanna , Paulson Daniel
Published: February 2017

Objective

Potentially incongruent research literatures suggest three divergent hypotheses about depressive symptomatology: (1) symptoms are recurrent; (2) later‐life depression results from high cerebrovascular burden (CVB); and (3) depressive symptoms contribute to comorbidities causing vascular burden. Past vascular depression research assumes that later‐life depressive symptoms relate uniquely to high CVB and not to prior, recurrent depression. This study examines these divergent hypotheses.

Methods

Data include 5175 participants across 18 years from the Wisconsin Longitudinal Study (mean age at 1993 baseline was 53 years; follow‐ups in 2004 and 2011). Depressive symptomatology was measured using the Center for Epidemiological Studies Depression. CVB was operationalized as hypertension, high blood sugar, diabetes, and other heart problems. Hypotheses were examined via a cross‐lagged structural equation model and logistic regression.

Results

Model fit was acceptable (root mean square error of approximation (RMSEA) = 0.047; comparative fit index = 0.963). Hypotheses 1 and 2 were supported. Depressive symptomatology at 2004 and 2011 follow‐ups was predicted by earlier depressive symptomatology and prior CVB. Hypothesis 3 was partially supported; depressive symptomatology in 2004 predicted subsequent CVB. Logistic regression results were that CVB predicted clinically significant depressive symptoms based on the Center for Epidemiological Studies Depression clinical cutoff.

Conclusions

Cerebrovascular burden in midlife predicts depressive symptomatology in later‐life, even after accounting for prior depressive symptomatology, supporting a fundamental assumption of the vascular depression hypothesis. Midlife depressive symptomatology also predicted escalation of CVB in later‐life. Results suggest a process model of later‐life depressive symptom development that interrelates CVB and depressive symptoms throughout the life span and have clinical implications for the interruption of this process through the integration of primary care and behavioral health specialists. Copyright © 2017 John Wiley & Sons, Ltd.
Consequences of clinical case management for caregivers: a systematic review
Authors: Corvol Aline , Dreier Adina , Prudhomm Joachim , Thyrian Jochen René , Hoffmann Wolfgang , Somme Dominique
Published: February 2017

Objective

Informal caregivers are deeply involved in the case management process. However, little is known about the consequences of such programs for informal caregivers. This systematic literature review, reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement, addressed the consequences of clinical case management programs, whether positive or negative, for caregivers of frail older persons or persons with dementia.

Methods

We systematically identified and analyzed published randomized trials and quasi‐experimental studies comparing case management programs to usual care, which discussed outcomes concerning caregivers.

Results

Sixteen studies were identified, and 12 were included after quality assessment. Seven identified at least one positive result for caregivers, and no negative effect of case management has been found. Characteristics associated with positive results for caregivers were a high intensity of case management and programs specifically addressed to dementia patients.

Conclusions

Despite the numerous methodological challenges in the assessment of such complex social interventions, our results show that case management programs can be beneficial for caregivers of dementia patients and that positive results for patients are achieved without increasing caregivers' burden. Copyright © 2017 John Wiley & Sons, Ltd.
Effects of chin‐up posture on the sequence of swallowing events
Authors: Calvo Irene , Sunday Kirstyn L. , Macrae Phoebe , Humbert Ianessa A.
Published: February 2017

Background

Chin‐up posture is frequently used to manage oral dysphagia after head and neck cancer. This prospective study investigates the effects of chin‐ups on the sequence of pharyngeal swallowing events.

Methods

Twelve healthy young adults performed 45 consecutive swallows of 5 mL water across 3 phases on videofluoroscopy: 5 swallows in the neutral head position; 30 swallows during chin‐up posture; and 10 swallows in the neutral head position. Swallowing kinematic and bolus flow measures for 9 swallowing events were recorded. Linear trends were analyzed across 30 chin‐up swallows; pairwise comparison was used to compare the 3 phases.

Results

Time to hyoid peak and laryngeal vestibule closure changed abruptly during chin‐up swallowing compared to the initial neutral position. No measure changed across 30 chin‐up swallows. Time of hyoid burst decreased upon returning to the neutral position.

Conclusion

Our findings indicate that chin‐up posture challenges the pharyngeal sequence of events for both swallowing kinematics and bolus flow. © 2017 Wiley Periodicals, Inc. Head Neck 39: 947–959, 2017
Experimental study on thermal performance of optimum PG brine as a radiator coolant
Authors: Sahoo Rashmi Rekha
Published: February 2017

The present study deals with the experimental impact of an alternative heat transfer fluids for overall performance improvement for radiators. Water and water mixed with anti‐freezing agents such as ethylene glycol (EG) and propylene glycol (PG) are the traditional coolants for an automotive radiator. Comparison of experimental and numerical analysis of optimum brine solution, that is 25% of propylene glycol and water as coolant for the rectangular fin radiator, has been well discussed. A closed loop test rig was designed, and fabricated with a wind tunnel section to achieve uniform velocity at the test section of the rectangular radiator and was tested for performance. Experimental runs were conducted at varying operating temperatures which included the runs for water, and an optimum propylene glycol brine solutions at 70 °C and 80 °C with various flow rates. Results show the energy performance of an optimum brine solution was nearly similar to that of water at high temperatures. The Nusselt number, heat transfer coefficient, and heat transfer rate for an optimum propylene glycol brine is nearly the same as water at 80 °C with a maximum deviation of 15%, 5.7%, and 6.6%, respectively, for theoretical and experimental result comparisons. Air side and coolant side pressure drops had a maximum deviation of 3.66% and 6.6%, respectively. Air and coolant exit temperatures had a deviation of 5% and 3.5%, respectively, with an air frontal velocity of 4.6 m/s in a rectangular fin radiator for an optimum brine solution used as coolant for the automotive radiator. The optimum propylene glycol brine may be environmentally beneficial.
Noncontingent reinforcement for the treatment of severe problem behavior: An analysis of 27 consecutive applications
Authors: Phillips Cara L. , Iannaccone Julia A. , Rooker Griffin W. , Hagopian Louis P.
Published: February 2017

Noncontingent reinforcement (NCR) is a commonly used treatment for severe problem behavior displayed by individuals with intellectual and developmental disabilities. The current study sought to extend the literature by reporting outcomes achieved with 27 consecutive applications of NCR as the primary treatment for severe problem behavior. All applications of NCR were included regardless of treatment outcome to minimize selection bias favoring successful cases. Participants ranged in age from 5 to 33 years. We analyzed the results across behavioral function and with regard to the use of functional versus alternative reinforcers. NCR effectively treated problem behavior maintained by social reinforcement in 14 of 15 applications, using either the functional reinforcer or alternative reinforcers. When we implemented NCR to treat problem behavior maintained by automatic reinforcement, we often had to add other treatment components to produce clinically significant effects (five of nine applications). Results provide information on the effectiveness and limitations of NCR as treatment for severe problem behavior.
Student Award for Outstanding Research Winner in the Undergraduate Category for the 2017 Society for Biomaterials Annual Meeting and Exposition, April 5–8, 2017, Minneapolis, Minnesota: Development and characterization of stimuli‐responsive hydrogel microcarriers for oral protein delivery
Authors: O'Connor Colleen , Steichen Stephanie , Peppas Nicholas A.
Published: February 2017

A family of pH‐responsive terpolymers composed of methacrylic acid (MAA), N‐vinyl pyrrolidone (NVP), and poly(ethylene glycol) monomethylether monomethacrylate (PEGMMA) have been developed and evaluated for their pH‐responsive swelling behavior, protein‐loading capabilities, and cytocompatibility. These terpolymer hydrogels, designated as P((MAA‐co‐NVP)‐g‐EG), were synthesized with varying PEG chain lengths and monomer feed ratios. The incorporation of MAA into the terpolymer structure was quantified with potentiometric titration. Equilibrium and dynamic swelling studies confirmed the pH‐responsive behavior of the hydrogel, with the system remaining collapsed/complexed in acidic pH conditions and swollen/decomplexed in neutral pH conditions. The ability of the hydrogels to partition protein into the swollen network was assessed for two model proteins of varying molecular weight: insulin and porcine growth hormone. Finally, the cytocompatibility of the hydrogels in the presence of two model intestinal cell lines was investigated and confirmed minimal cytotoxicity at and below 2.5 mg/mL. The developed P((MAA‐co‐NVP)‐g‐EG) hydrogels exhibit unique properties that could potentially be utilized for drug delivery and separation applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1243–1251, 2017.
NSI‐189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats
Authors: Tajiri Naoki , Quach David M. , Kaneko Yuji , Wu Stephanie , Lee David , Lam Tina , Hayama Ken L. , Hazel Thomas G. , Johe Karl , Wu Michael C. , Borlongan Cesar V.
Published: February 2017

Enhancing neurogenesis may be a powerful stroke therapy. Here, we tested in a rat model of ischemic stroke the beneficial effects of NSI‐189, an orally active, new molecular entity (mol. wt. 366) with enhanced neurogenic activity, and indicated as an anti‐depressant drug in a clinical trial (Fava et al., , Molecular Psychiatry, DOI: 10.1038/mp.2015.178) and being tested in a Phase 2 efficacy trial (ClinicalTrials.gov, , ClinicalTrials.gov Identifier: NCT02695472) for treatment of major depression. Oral administration of NSI‐189 in adult Sprague–Dawley rats starting at 6 hr after middle cerebral artery occlusion, and daily thereafter over the next 12 weeks resulted in significant amelioration of stroke‐induced motor and neurological deficits, which was maintained up to 24 weeks post‐stroke. Histopathological assessment of stroke brains from NSI‐189‐treated animals revealed significant increments in neurite outgrowth as evidenced by MAP2 immunoreactivity that was prominently detected in the hippocampus and partially in the cortex. These results suggest NSI‐189 actively stimulated remodeling of the stroke brain. Parallel in vitro studies further probed this remodeling process and demonstrated that oxygen glucose deprivation and reperfusion (OGD/R) initiated typical cell death processes, which were reversed by NSI‐189 treatment characterized by significant attenuation of OGD/R‐mediated hippocampal cell death and increased Ki67 and MAP2 expression, coupled with upregulation of neurogenic factors such as BDNF and SCF. These findings support the use of oral NSI‐189 as a therapeutic agent well beyond the initial 6‐hr time window to accelerate and enhance the overall functional improvement in the initial 6 months post stroke.
Metastatic neuroblastoma diagnosed on prenatal sonographic examination performed for decreased fetal movement
Authors: Chapa Hector O. , Geddie Steven Gywnn , Flores Rebecca
Published: February 2017

We report a case of fetal neuroblastoma presenting with massive liver metastasis diagnosed during the biophysical profile sonographic examination performed for decreased fetal movement. The patient presented at 37 weeks' gestation with limited fetal movement over 24 hours. Biophysical profile showed marked polyhydramnios and an enlarged abdomen filled with a homogeneous mass lesion suspicious for liver metastasis. Primary urgent cesarean section was performed revealing a cachectic neonate with a rigid and grossly distended abdomen. Neonatal evaluation confirmed the etiology of the abdominal mass to be liver metastasis from neuroblastoma. The child died on the 46th day. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:502–506, 2017
Inclusion of Carbonyl Groups of Benzo[b]thiophene‐2,5‐dione into Amidrazones: Synthesis of 1,2,4‐triazine‐5,6‐diones
Authors: Aly Ashraf A. , Ramadan Mohamed , Morsy Nesrin M. , Elkanzi N.A.A.
Published: February 2017

Amidrazones reacted with benzo[b]thiophene‐2,3‐dione at refluxing ethanol and catalyzed with trimethylamine to give 4‐aryl‐3‐phenyl‐1,2,4‐triazine‐5,6‐dione derivatives. The structure of the obtained products was proved by IR, mass, NMR spectra and elemental analyses. The reaction mechanism is also discussed.
Design, Synthesis, and Antimicrobial Evaluation of some Novel Pyridine, Coumarin, and Thiazole Derivatives
Authors: Khidre Rizk E. , El‐Gogary Sameh R. , Mostafa Mohamed S.
Published: February 2017

Treatment of 2‐cyano‐N′‐(1‐(pyridin‐2‐yl)ethylidene)acetohydrazide 1 with aromatic/heterocyclic aldehydes 2a–f gave arylidene derivatives 3a–f. Polysubstituted pyridine derivatives 4a,b were prepared either from reaction of arylidene 3a,b with malononitrile or from reaction of acetohydrazide 1 with arylidenemalononitrile 5a,b. Cyclocondensation of acetohydrazide 1 with salicylaldehyde derivatives and acetylacetone furnished pyrido‐coumarins 6,7 and 2‐pyridone‐3‐carbonitrile 8, respectively. In addition, pyrido‐thiazoles 13 and 15 were obtained through reaction of 2‐(1‐(pyridin‐2‐yl)ethylidene)hydrazinecarbothioamide 11 with hydrazonyl chlorides and α‐haloketones, respectively. The structures of synthesized compounds were elucidated with spectral and elemental data. The antimicrobial activity of the synthesized compounds was studied.
Diagnostic value of renal perfusion in patients with chronic kidney disease using 3D arterial spin labeling
Authors: Cai Yu‐zhe , Li Zhi‐cheng , Zuo Pan‐li , Pfeuffer Josef , Li Yu‐ming , Liu Fang , Liu Rong‐bo
Published: February 2017

Purpose

To evaluate the diagnostic value of 3D arterial spin labeling (ASL) for noninvasive quantification of renal blood flow (RBF) in patients with chronic kidney disease (CKD).

Materials and Methods

CKD patients (n = 27) and healthy volunteers (n = 36) underwent renal 3T ASL magnetic resonance imaging, with inversion times from 1200 to 2000 msec for volunteers in the preliminary test, and 1800 to 2000 msec for volunteers and CKD patients in the formal experiments. The cortical RBFs were compared, and a correlation between RBF and estimated glomerular filtration rate (eGFR) was evaluated.

Results

For healthy volunteers, RBF values increased with TIs from 1200 to 1600 msec, but were almost constant at TIs from 1600 to 2000 msec. The cortical RBF values of CKD patients were lower than that of healthy volunteers at TIs from 1800 to 2000 msec. In addition, the CKD patients had lower cortical RBF values than the healthy volunteers (P < 0.01 for both), and their RBF values positively correlated with eGFR.

Conclusion

3D ASL is a potential noninvasive method for measuring renal perfusion that can provide valuable information for clinical CKD diagnosis.

Level of Evidence: 1

Technical Efficacy: Stage 3

J. MAGN. RESON. IMAGING 2017;46:589–594
Respiratory motion artifacts during arterial phase imaging with gadoxetic acid: Can the injection protocol minimize this drawback?
Authors: Polanec Stephan H. , Bickel Hubert , Baltzer Pascal A.T. , Thurner Patrick , Gittler Florian , Hodge Jacqueline C. , Bashir Mustafa R. , Ba‐Ssalamah Ahmed
Published: February 2017

Purpose

To determine which of three gadoxetic acid injection techniques best reduced the contrast‐related arterial‐phase motion artifacts.

Materials and Methods

This Institutional Review Board (IRB)‐approved, retrospective study included a cohort of 78 consecutive patients who each had serial gadoxetic acid‐enhanced 3.0T magnetic resonance imaging (MRI) of the liver (0.025 mmol/kg body weight) performed with at least two of three injection techniques: M1 test bolus, undiluted, power‐injected 1 mL/s; M2 test bolus, diluted 50% with saline, power‐injected 1 mL/s; M3 fixed delay, undiluted, manually injected. Blinded to the injection method, three readers independently rated the randomized images for arterial‐phase motion artifacts, arterial‐phase timing, and arterial‐phase lesion visibility using a four‐point Likert scale.

Results

Regarding respiratory artifacts, gadoxetic acid arterial‐phase images were judged better with M3 (2.7 ± 0.7) and were significantly less than those with M1 (2.1 ± 1.1) (P = 0.0001). Arterial‐phase M2 (2.50 ± 0.89) images were rated significantly better than arterial‐phase M1 images (P = 0.012), but the difference between arterial‐phase images with M3 and M2 scores was not statistically significant (P = 0.49). Arterial‐phase timing was significantly better for M1 compared to M3, and for M2 compared to M3 (P < 0.0001 for both). The area under the curve was 0.59–0.68. However, there was no significant difference between M1 and M2 (P = 0.35). With regard to arterial‐phase lesion visibility, there was no significant difference in the ratings between any of the three injection techniques (P = 0.29–0.72). Interreader agreement was moderate to substantial (κ = 0.41–0.62).

Conclusion

A diluted, power‐injected protocol (M2) seems to provide good timing and minimize artifacts compared with two other injection methods. No significant difference was found in lesion visibility between these three methods.

Level of Evidence: 3

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2017;46:1107–1114.
Cowpea: a legume crop for a challenging environment
Authors: Carvalho Márcia , Lino‐Neto Teresa , Rosa Eduardo , Carnide Valdemar
Published: February 2017

Cowpea is a grain legume native from Africa and is a primary source of protein for millions of people in sub‐Saharan Africa and other parts of the developing world. The main important characteristics of this crop include a good protein quality with a high nutritional value, its nitrogen‐fixing ability, and an ability to be more drought‐ and heat‐tolerant than most of its legume relatives. In a research perspective, studies of cowpea are relatively scarce, despite its relevance to agriculture in the developing world and its resilience to stress. The present review provides an overview of different aspects of cowpea, with a special emphasis on the molecular markers for assessing genetic diversity, as well as on biochemical and transcriptomic data with respect to evaluating cowpea drought stress tolerance. The integration of both datasets will be useful for the improvement of cowpea because research on drought stress tolerance is of major interest for this crop in a challenging environment. © 2017 Society of Chemical Industry
On the Phase Shifts in the Dynamics of the H2O2–Na2S2O3–H2SO4–CuSO4 Oscillator Revealed by Comparison of Potentiometric Responses of Different Indicator Electrodes
Authors: Jędrusiak Mikołaj , Matyszczak Grzegorz , Orlik Marek
Published: February 2017

The dynamics of the H2O2–Na2S2O3–H2SO4–CuSO4 homogeneous pH oscillator was studied in the flow reactor potentiometrically using different sensors: platinum electrode, Cu(II) ion‐selective electrode (Cu‐ISE), and pH‐electrode. It was found that for the flow rates close to two bifurcation values, between which the oscillations exist, there is a detectable phase shift between the response of the Cu‐ISE and other electrodes, while it practically vanishes for the intermediate flow rates. To explain both the oscillations of the Cu‐ISE potential and the relevant phase shift, the system's dynamics was studied both experimentally and numerically. The literature kinetic mechanism of the pH oscillator was extended for the dynamics of the copper(II) and copper(I) species in the form of thiosulfate complexes, and kinetic parameters of the redox equilibria, ensuring the oscillations, were estimated. It was found that the phase shift at the relatively low flow rates occurs due to limited efficiency of the supply of CuSO4 catalyst, as the species of lowest concentration, to the reactor, and therefore it can be minimized either by increasing the flow rate of all reactants or, alternatively, by enhancing the model concentration of CuSO4 in the feeding stream, for its fixed flow rate. This work is one more proof that it is useful to monitor the dynamics of the homogeneous oscillatory systems with more than one electrode, if the experimental potential–time courses are to be explained in terms of an appropriate kinetic mechanism.
The Search for Potent, Small‐Molecule HDACIs in Cancer Treatment: A Decade After Vorinostat
Authors: Zagni Chiara , Floresta Giuseppe , Monciino Giulia , Rescifina Antonio
Published: February 2017

Histone deacetylases (HDACs) play a crucial role in the remodeling of chromatin, and are involved in the epigenetic regulation of gene expression. In the last decade, inhibition of HDACs came out as a target for specific epigenetic changes associated with cancer and other diseases. Until now, more than 20 HDAC inhibitors (HDACIs) have entered clinical studies, and some of them (e.g., vorinostat, romidepsin) have been approved for the treatment of cutaneous T‐cell lymphoma. This review provides an overview of current knowledge, progress, and molecular mechanisms of HDACIs, covering a period from 2011 until 2015.
A molecular analysis of the GBA gene in Caucasian South Africans with Parkinson's disease
Authors: Barkhuizen Melinda , Anderson David G. , van der Westhuizen Francois H. , Grobler Anne F.
Published: February 2017

Background

The molecular basis of Parkinson's disease in South African population groups remains elusive. To date, substitutions in the GBA gene are the most common large‐effect genetic risk factor for Parkinson's disease. The primary objective of this study was to determine the prevalence of GBA substitutions in South Africans with idiopathic Parkinson's disease.

Methods

Participants were recruited from tertiary hospitals in the Gauteng Province in South Africa. All participants were screened for substitutions in GBA exon 8‐11 and the full coding region was analysed in 20 participants. Peripheral β‐glucocerebrosidase enzymatic activity of GBA‐carriers was measured in mixed leukocytes.

Results

Of 105 Caucasian Parkinson's disease participants (82.7% Afrikaner) with an average age of disease onset of 61.9 ± 12.2 years and 40 controls (age 73.4 ± 12.4 years) were included. Heterozygous GBA substitutions were identified in 12.38% of affected participants (p.G35A, p.E326K, p.I368T, p.T369M, p.N370S, p.P387L and p.K441N) and 5.00% of controls (p.E326K and p.T369M). The substitutions ranged from predicted benign to moderately damaging; with p.E326K and p.T369M most prevalent, followed by the Afrikaner Gaucher disease substitution p.P387L. Severe Gaucher disease mutations, like p.L444P, were absent in this cohort. Enzyme activity analysis revealed a nonsignificant reduction in the GBA‐Parkinson's disease individuals (14.49 ± 2.30 nmol/h/mg protein vs. 15.98 ± 3.06 nmol/h/mg in control samples). GBA substitutions occur in both young‐onset and late‐onset Parkinson's cases in the cohort.

Conclusion

Mild GBA substitutions that may not cause Gaucher disease were a common risk factor for Parkinson's disease in the participant group.
Determination of partition coefficients using 1H NMR spectroscopy and time domain complete reduction to amplitude‐frequency table (CRAFT) analysis
Authors: Soulsby David , Chica Jeryl A. M.
Published: February 2017

We have developed a simple, direct and novel method for the determination of partition coefficients and partitioning behavior using 1H NMR spectroscopy combined with time domain complete reduction to amplitude‐frequency tables (CRAFT). After partitioning into water and 1‐octanol using standard methods, aliquots from each layer are directly analyzed using either proton or selective excitation NMR experiments. Signal amplitudes for each compound from each layer are then extracted directly from the time domain data in an automated fashion and analyzed using the CRAFT software. From these amplitudes, log P and log D7.4 values can be calculated directly. Phase, baseline and internal standard issues, which can be problematic when Fourier transformed data are used, are unimportant when using time domain data. Furthermore, analytes can contain impurities because only a single resonance is examined and need not be UV active. Using this approach, we examined a variety of pharmaceutically relevant compounds and determined partition coefficients that are in excellent agreement with literature values. To demonstrate the utility of this approach, we also examined salicylic acid in more detail demonstrating an aggregation effect as a function of sample loading and partition coefficient behavior as a function of pH value. This method provides a valuable addition to the medicinal chemist toolbox for determining these important constants. Copyright © 2017 John Wiley & Sons, Ltd.
Convergence analysis of the ChebFilterCG algorithm
Authors: Sadkane Miloud , Touhami Ahmed
Published: February 2017

The ChebFilterCG algorithm, proposed by Golub, Ruiz, and Touhami [SIAM J. Matrix Anal. Appl. 29 (2007), pp. 774‐795] is an iterative method that combines Chebyshev filter and conjugate gradient for solving symmetric positive definite linear systems with multiple right‐hand sides. The Chebyshev filter is used to produce initial residuals rich in eigenvectors corresponding to the smallest eigenvalues, which are then used in the initial phase of the conjugate gradient. This paper presents a convergence analysis of ChebFilterCG. In particular, it is shown theoretically and numerically that the algorithm yields an approximation of the invariant subspace associated with the smallest eigenvalues that can be recycled for solving several linear systems with the same matrix and different right‐hand sides. A refined error bound when solving these systems is also given. The choice and influence of the Chebyshev filtering steps is discussed. Numerical experiments are described to illustrate that the Chebyshev filter does not degrade the distribution of the smallest eigenvalues and highlight the effect of rounding errors when large outlying eigenvalues are present. Finally, it is shown that the method may become more effective when an additional Chebyshev filtering step is used in the initialization phase of ChebFilterCG.
Hunted or Scavenged Neanderthals? Taphonomic Approach to Hominin Fossils with Carnivore Damage
Authors: Camarós E. , Cueto M. , Rosell J. , Díez J. C. , Blasco R. , Duhig C. , Darlas A. , Harvati K. , Jordá J. , Montes L. , Villaverde V. , Rivals F.
Published: February 2017

Carnivore damage on Neanderthal fossils is a much more common taphonomic modification than previously thought. Its presence could have different explanations, including predatory attacks or scavenging scenarios, which are both situations with important implications concerning Neanderthal behaviour. In the present paper, we analyse several Neanderthal hominin fossils from a taphonomic and forensic perspective in order to infer the nature of the modifications observed on the bone surfaces. Fossils displaying carnivore modifications from Spain, Germany, Belgium and Greece are evaluated from a taphonomic perspective for the first time in a significant sample of hominin specimens. Our results show that the materials analysed have been modified by small to large carnivores and that both attacks and strictly carnivore scavenging events can be inferred. This study also points out the importance of developing taphonomic approaches to the analysis of hominin bone surfaces, which can contribute significantly to knowledge of several aspects of Neanderthal behaviour. Copyright © 2017 John Wiley & Sons, Ltd.
Partially bio‐based tri‐ and hexaallyl monomers: Synthesis from naturally occurringmyo‐inositol and polyaddition with dithiols
Authors: Sudo Atsushi , Shirakawa Yugo , Sakue Tomio
Published: February 2017

myo‐Inositol, a naturally occurring cyclic hexaol, was converted to 2,4,6‐tri‐O‐allyl‐myo‐inositol and 1,2,3,4,5,6‐hexa‐O‐allyl‐myo‐inositol. Polyaddition of the former product, a tri(allyl ether) bearing three hydroxyl groups, with dithiols yielded the corresponding networked polymers. Their glass transition temperatures (Tgs) were higher than those of networked polymers formed by the polyaddition of 1,3,5‐tri‐O‐methyl‐2,4,6‐tri‐O‐allyl‐myo‐inositol. This implied the reinforcement of the networks by hydrogen bonding between the hydroxyl groups. Polyaddition of the latter product, a hexa(allyl ether), with dithiols yielded the corresponding networked polymers with much higherTgs than those of all of the aforementioned networked polymers. This implied that efficient use of the hexafunctional monomer leads to the formation of more densely crosslinked polymers. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem.2017,55, 1524–1529