bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐Performance Oxygen Reduction Electrocatalyst Derived from Polydopamine and Cobalt Supported on Carbon Nanotubes for Metal–Air Batteries
Authors: Liu Yiling , Chen Fengjiao , Ye Wen , Zeng Min , Han Na , Zhao Feipeng , Wang Xinxia , Li Yanguang
Published: February 2017

The development of nonprecious metal‐based electrocatalysts for the oxygen reduction reaction holds the decisive key to many energy conversion devices. Among several potential candidates, transition metal and nitrogen co‐doped carbonaceous materials are the most promising, yet their activity and stability are still insufficient to meet the needs of practical applications. In this study, a core–shell hybrid electrocatalyst is developed via the self‐polymerization of dopamine and cobalt on carbon nanotubes (CNTs), followed by high‐temperature pyrolysis. The polymer‐derived carbonaceous shell contains abundant structural defects and facilitates the formation of CoN/C active sites, whereas the graphitic carbon nanotube core provides high electrical conductivity and corrosion resistance. These two components separately fulfill different functionalities, and jointly afford the catalyst with excellent electrochemical performance. In 1 m KOH, CoN/CNT exhibits a positive half‐wave potential of ≈0.91 V, low peroxide yield of <7%, as well as great stability. When used as the air catalyst of primary Zn–air and Al–air batteries, this hybrid electrocatalyst enables large discharge current density, high peak power density, and prolonged operation stability.
White Afterglow Room‐Temperature Emission from an Isolated Single Aromatic Unit under Ambient Condition
Authors: Hirata Shuzo , Vacha Martin
Published: February 2017

Single aromatic structures generally do not generate emission with a white afterglow (i.e., a lifetime longer than 1 s). This study shows white afterglow room‐temperature (RT) emission from an isolated single aromatic structure doped into a rigid amorphous matrix in air. 2,5,8,11,14,17‐Hexa(4‐(2‐ethyl‐hexyl‐)‐hexa‐peri‐hexabenzocoronene (6EhHBC) doped into β‐estradiol shows blue‐green thermally activated delayed fluorescence (TADF), as well as red phosphorescence with a lifetime of 3.9 s, at RT in air. The energy difference between the lowest singlet excited state and the lowest triplet excited state (ΔE
ST) of 6EhHBC is reduced to below 0.5 eV because of the effective separation between the two molecular orbitals related to fluorescence caused by the large 2D symmetric extension of the planar aromatic cyclic structures. The long‐lived RT triplet state of 6EhHBC in the rigid host matrix enables an efficient TADF with ΔE
ST ≈ 0.5 eV at RT, as well as a red afterglow RT phosphorescence, leading to white afterglow RT emission.
Hematology patient reported symptom screen to assess quality of life for AL amyloidosis
Authors: Warsame Rahma , Kumar Shaji K. , Gertz Morie A. , Lacy Martha Q. , Buadi Francis K. , Hayman Suzanne R. , Leung Nelson , Dingli David , Lust John A. , Lin Yi , Russell Stephen , Kapoor Prashant , Go Ronald S. , Kourelis Taxiarchis , Gonsalves Wilson , Zeldenrust Steven R. , Kyle Robert A. , Vincent Rajkumar S. , Zemla Tyler , Sloan Jeffrey , Dispenzieri Angela
Published: February 2017

Patients with light chain amyloidosis (AL) often have delayed diagnosis and present with significant symptomatology; this may result in decreased quality of life (QOL). We prospectively employ a “Hematology Patient Reported Symptom Screen” (HPRSS), which is three questions about fatigue, pain, and QOL, scored 0–10. The aim of this study is to better understand QOL and determine if HPRSS parameters predict for clinical outcomes. From 2009 to 2014, 302 newly diagnosed AL patients were included. Baseline median scores [interquartile range] for fatigue, pain, and QOL were 6 [3,7], 2 [0,5], 5 [3,8], respectively. Median overall survival was 53 months, with 102 (34%) deaths in the first year. There were significant differences in baseline HPRSS between those that lived longer than one year and early death patients in the domains of fatigue (5 [IQR 3, 7] vs. 7 [IQR 5, 8], P < 0.0001) and QOL (6 [IQR 4, 8] vs. 5 [IQR 3, 7], P = 0.006). On univariate analysis fatigue, QOL, physician‐reported performance status, autologous stem cell transplant (ASCT), and Mayo stage were prognostic for survival. On multivariate analysis Mayo stage, ASCT, and baseline fatigue remained independently prognostic. When analyses were restricted to the 125 patients with HPRSS measurements at 12 months, we found that over time QOL scores improved significantly 6 [IQR 3.5, 8] → 7 [IQR 5, 8] (P = 0.01). Asking AL patients to rate their fatigue and QOL has predictive value. Baseline patient reported fatigue is an independent prognostic factor for survival. Survival at one year was associated with significant improvement in QOL.
Blepharocheilodontic (BCD) syndrome: New insights on craniofacial and dental features
Authors: Awadh Wael , Kiukkonen Anu , Nieminen Pekka , Arte Sirpa , Hurmerinta Kirsti , Rice David P.
Published: February 2017

Blepharocheilodontic (BCD) syndrome is a rare condition characterized by bilateral cleft lip and palate (BCLP), eyelid abnormalities, and oligodontia. Despite orofacial clefting and oligodontia being central features of the condition, detailed reports of dental and craniofacial characteristics are scarce. The aim of this study was to analyze the dental and craniofacial features in a group of patients with BCD syndrome (three of which were related). Cephalometric radiographic analyses were performed on BCD syndrome patients (all radiographs taken at age 8 years) and compared to 40 randomly selected age‐matched controls (20 non‐syndromic BCLP, 20 non‐cleft). Also, we assessed clinical records, photographs, dental study casts, and dental radiographs to determine the extent and pattern of tooth agenesis, dental morphology and malocclusion. BCD syndrome patients showed a very severe skeletal III malocclusion (maxillary–mandibular sagittal discrepancy) and reduced anterior lower face measurement compared to non‐syndromic BCLP and non‐cleft controls (P = 0.001, P = 0.027). All patients exhibited oligodontia (mean number of missing permanent teeth 13.7, range 7–17). All patients exhibited missing upper central and lateral incisor, upper canine and premolar teeth. Variations in dental morphology included taurodontism, conical‐shaped teeth, and notching of the incisal edges. All patients had a short and narrow maxilla which translated into anterior and posterior cross bites. We conclude that, in our BCD syndrome group, the craniofacial skeletal defects are more severe than patients with BCLP. The pattern of tooth agenesis is unusual as it included teeth that are normally highly resistant to agenesis, namely upper central incisor and canine teeth. © 2017 Wiley Periodicals, Inc.
Novel LINS1 missense mutation in a family with non‐syndromic intellectual disability
Authors: Sheth Jayesh , Ranjan Gyan , Shah Krati , Bhavsar Riddhi , Sheth Frenny
Published: February 2017

Newer sequencing technologies decipher molecular variations and increase the knowledge of pathogenesis of complex diseases like intellectual disability (ID), affecting 2–3% of the population. We report a novel family with a missense mutation in LINS1 as a cause for non‐syndromic ID. Clinical exome sequencing for ID related genes carried out for a male with dysmorphism, mutism, and cognitive delay was uninformative. Subsequently, “pathogenic” and “likely pathogenic” variants associated with other inherited disorders were searched for as secondary findings. Further, PCR‐RFLP carried out in other family members confirmed the result. A novel missense variant (c.937G>A) in exon 5 of LINS1 was detected in the proband. His affected elder brother was homozygous and the parents were heterozygous respectively, for the mutation. No mutation was observed in his unaffected sister. Mutations in LINS1 were suspected in this non‐syndromic ID case with mutism. LINS1 alterations affect ELAV1 expression and result in reduction in the commissural axonal growth, thus affecting peripheral and central neuronal function. LINS1 acts in association with β‐catenin to influence WNT1 signaling. It is hypothesized that mutations in LINS1 may alter HuR expression during neural differentiation, leading to ID in humans. © 2017 Wiley Periodicals, Inc.
F508del genotype in endoscopic sinus surgery: do differences in outcomes exist between genotypic subgroups?
Authors: Halderman Ashleigh A. , West Natalie , Benke James , Roxbury Christopher R. , Lin Sandra Y.
Published: February 2017

Background

The impact of endoscopic sinus surgery (ESS) on pulmonary function in cystic fibrosis (CF) patients with chronic rhinosinusitis remains unclear, as studies have demonstrated conflicting results. To date, no study has looked specifically at the impact of CF genotype on lung function after ESS. In this study, we reviewed changes in pulmonary function test (PFT) results after ESS in F508del homozygotes and heterozygotes.

Methods

The charts of 25 patients with CF without prior lung transplant, who underwent ESS performed by the same surgeon between the period of July 2005 to July 2015, were retrospectively reviewed. Data including genotype and PFT results were collected. Patients were grouped based on genotype. Pre‐ and postoperative PFTs were compared.

Results

Some differences in PFT outcomes after ESS could be seen on subgroup analyses. For example, when considered as a whole group, the overall cohort showed a significant improvement from preoperative FEV1 levels at 6 months after surgery (p = 0.0127). Interestingly, on subgroup analysis, the heterozygous group saw significant improvements from preoperative FEV1 levels at 6 and 12 months (p = 0.0155 and p = 0.0333, respectively). No significant improvements were seen from “baseline” FEV1 in either group at any timepoint.

Conclusion

Prior studies investigating the impact of ESS on pulmonary function in CF patients have shown conflicting results. To our knowledge, those earlier udies did not separate and compare different genotypes, which may have introduced heterogeneity in their patient populations. Our study suggests that grouping CF patients more strictly according to genotype or disease severity when investigating outcomes may reveal differences among various subgroups.
Hydronium‐Ion Batteries with Perylenetetracarboxylic Dianhydride Crystals as an Electrode
Authors: Wang Xingfeng , Bommier Clement , Jian Zelang , Li Zhifei , Chandrabose Raghu S. , Rodríguez‐Pérez Ismael A. , Greaney P. Alex , Ji Xiulei
Published: February 2017

We demonstrate for the first time that hydronium ions can be reversibly stored in an electrode of crystalline 3,4,9,10‐perylenetetracarboxylic dianhydride (PTCDA). PTCDA exhibits a capacity of 85 mAh g−1 at 1 A g−1 after an initial conditioning process. Ex situ X‐ray diffraction revealed reversible and significant structure dilation upon reduction of PTCDA in an acidic electrolyte, which can only be ascribed to hydronium‐ion intercalation. The lattice expansion upon hydronium storage was theoretically explored by first‐principles density functional theory (DFT) calculations, which confirmed the hydronium storage in PTCDA.
High‐Power Actuation from Molecular Photoswitches in Enantiomerically Paired Soft Springs
Authors: Aßhoff Sarah J. , Lancia Federico , Iamsaard Supitchaya , Matt Benjamin , Kudernac Tibor , Fletcher Stephen P. , Katsonis Nathalie
Published: February 2017

Motion in plants often relies on dynamic helical systems as seen in coiling tendrils, spasmoneme springs, and the opening of chiral seedpods. Developing nanotechnology that would allow molecular‐level phenomena to drive such movements in artificial systems remains a scientific challenge. Herein, we describe a soft device that uses nanoscale information to mimic seedpod opening. The system exploits a fundamental mechanism of stimuli‐responsive deformation in plants, namely that inflexible elements with specific orientations are integrated into a stimuli‐responsive matrix. The device is operated by isomerization of a light‐responsive molecular switch that drives the twisting of strips of liquid‐crystal elastomers. The strips twist in opposite directions and work against each other until the pod pops open from stress. This mechanism allows the photoisomerization of molecular switches to stimulate rapid shape changes at the macroscale and thus to maximize actuation power.
Anti–Citrullinated Protein Antibodies Are Associated With Neutrophil Extracellular Traps in the Sputum in Relatives of Rheumatoid Arthritis Patients
Authors: Demoruelle M. Kristen , Harrall Kylie K. , Ho Linh , Purmalek Monica M. , Seto Nickie L. , Rothfuss Heather M. , Weisman Michael H. , Solomon Joshua J. , Fischer Aryeh , Okamoto Yuko , Kelmenson Lindsay B. , Parish Mark C. , Feser Marie , Fleischer Chelsie , Anderson Courtney , Mahler Michael , Norris Jill M. , Kaplan Mariana J. , Cherrington Brian D. , Holers V. Michael , Deane Kevin D.
Published: February 2017

Objective

Studies suggest that rheumatoid arthritis (RA)–related autoimmunity is initiated at a mucosal site. However, the factors associated with the mucosal generation of this autoimmunity are unknown, especially in individuals who are at risk of future RA. Therefore, we tested anti–cyclic citrullinated peptide (anti‐CCP) antibodies in the sputum of RA‐free first‐degree relatives (FDRs) of RA patients and patients with classifiable RA.

Methods

We evaluated induced sputum and serum samples from 67 FDRs and 20 RA patients for IgA anti‐CCP and IgG anti‐CCP, with cutoff levels for positivity determined in a control population. Sputum was also evaluated for cell counts, neutrophil extracellular traps (NETs) using sandwich enzyme‐linked immunosorbent assays for protein/nucleic acid complexes, and total citrulline.

Results

Sputum was positive for IgA and/or IgG anti‐CCP in 14 of 20 RA patients (70%) and 17 of 67 FDRs (25%), including a portion of FDRs who were serum anti‐CCP negative. In the FDRs, elevations of sputum IgA and IgG anti‐CCP were associated with elevated sputum cell counts and NET levels. IgA anti‐CCP was associated with ever smoking and with elevated sputum citrulline levels.

Conclusion

Anti‐CCP is elevated in the sputum of FDRs, including seronegative FDRs, suggesting that the lung may be a site of anti‐CCP generation in this population. The association of anti‐CCP with elevated cell counts and NET levels in FDRs supports a hypothesis that local airway inflammation and NET formation may drive anti‐CCP production in the lung and may promote the early stages of RA development. Longitudinal studies are needed to follow the evolution of these processes relative to the development of systemic autoimmunity and articular RA.
Nitrogen‐Bridged Metallodiazaporphyrin Dimers: Synergistic Effects of Nitrogen Bridges and meso‐Nitrogen Atoms on Structure and Properties
Authors: Kawamata Masahiro , Sugai Takuma , Minoura Mao , Maruyama Yasuhisa , Furukawa Ko , Holstrom Cole , Nemykin Victor N. , Nakano Haruyuki , Matano Yoshihiro
Published: February 2017

NH‐bridged and pyrazine‐fused metallodiazaporphyrin dimers have been prepared from nickel(II) and copper(II) complexes of 3‐amino‐5,15‐diazaporphyrin by Pd‐catalyzed C−N cross‐coupling and oxidative dimerization reactions, respectively. The synergistic effects of the nitrogen bridges and meso‐nitrogen atoms play major roles in enhancing the light‐harvesting properties and delocalization of an electron spin over the entire π‐skeletons of the metallodiazaporphyrin dimers.
An improved method for purification and refolding of recombinant HIV Vif expressed inEscherichia coli
Authors: Duarte Carlos A. , Palomino Mickel
Published: February 2017

Virion infectivity factor (Vif) is a 23 kDa protein that protects HIV‐1 from deamination of its proviral DNA by APOBEC3G. The active form of Vif is a multimer that interacts simultaneously with CBF‐beta, the elongin B and C subunits, Cullin 5, and APOBEC3G to form a ubiquitin ligase complex targeting the latter for degradation. Vif clearly represents an attractive target for developing novel antiviral drugs for the therapy of HIV/AIDS, and this goal requires a source of well folded, readily available protein. For that purpose, we have clonedVifin the pET28a expression vector, expressing the resulting His‐tagged recombinant protein in the BL21(DE3)Escherichia colistrain. After lysis, Vif was solubilized from the insoluble fraction with 6 M guanidinium chloride and purified by denaturing immobilized‐metal affinity chromatography, refolding the protein afterwards by dialysis. The use of 2‐(N‐morpholino)ethanesulfonic acid buffer at pH 6.2 and the presence of EDTA improved Vif refolding yields by reducing the formation of insoluble aggregates. The purified protein was bound by two monoclonal antibodies against sequential and conformational epitopes located at the C and N terminus, respectively.
The role of genes, intelligence, personality, and social engagement in cognitive performance in Klinefelter syndrome
Authors: Skakkebæk Anne , Moore Philip J. , Pedersen Anders Degn , Bojesen Anders , Kristensen Maria Krarup , Fedder Jens , Laurberg Peter , Hertz Jens Michael , Østergaard John Rosendahl , Wallentin Mikkel , Gravholt Claus Højbjerg
Published: February 2017

Introduction

The determinants of cognitive deficits among individuals with Klinefelter syndrome (KS) are not well understood. This study was conducted to assess the impact of general intelligence, personality, and social engagement on cognitive performance among patients with KS and a group of controls matched for age and years of education.

Methods

Sixty‐nine patients with KS and 69 controls were assessed in terms of IQ, NEO personality inventory, the Autism Spectrum Quotient (AQ) scale, and measures of cognitive performance reflecting working memory and executive function.

Results

Patients with KS performed more poorly on memory and executive‐function tasks. Patients with KS also exhibited greater neuroticism and less extraversion, openness, and conscientiousness than controls. Memory deficits among patients with KS were associated with lower intelligence, while diminished executive functioning was mediated by both lower intelligence and less social engagement.

Conclusion

Our results suggest that among patients with KS, memory deficits are principally a function of lower general intelligence, while executive‐function deficits are associated with both lower intelligence and poorer social skills. This suggests a potential influence of social engagement on executive cognitive functioning (and/or vice‐versa) among individuals with KS, and perhaps those with other genetic disorders. Future longitudinal research would be important to further clarify this and other issues discussed in this research.
A genetic variant within STS previously associated with inattention in boys with attention deficit hyperactivity disorder is associated with enhanced cognition in healthy adult males
Authors: Humby Trevor , Fisher Amelia , Allen Christopher , Reynolds Meghann , Hartman Annette , Giegling Ina , Rujescu Dan , Davies William
Published: February 2017

Introduction

The enzyme steroid sulfatase (STS) converts sulfated steroids to their non‐sulfated forms. Deficiency for this enzyme is associated with inattention but preserved response control. The polymorphism rs17268988 within the X‐linked STS gene is associated with inattentive, but not other, symptoms in boys with attention deficit hyperactivity disorder (ADHD).

Methods

We initially tested whether rs17268988 genotype was associated with attention, response control, and underlying aspects of cognition, using questionnaires and neuropsychological tasks, in two independent cohorts of healthy adult males. In an additional analysis based upon existing data, the performance of mice with genetic or pharmacological manipulations of the STS axis under attentionally demanding conditions was investigated.

Results

G‐allele carriers at rs17268988 exhibited reduced reaction time, enhanced attention, and reduced reaction time variability relative to C‐allele carriers. Mice with genetic or pharmacological manipulations of the STS axis were shown to have perturbed reaction time variability.

Discussion

Our findings provide additional support for an association between rs17268988 genotype and attention, which may be partially mediated by reaction time variability; they also indicate that, in contrast to the situation in boys with ADHD, in healthy men, the G‐allele at rs17268988 is associated with enhanced cognition. As reaction time variability is a predictor of well‐being, rs17268988 genotype may represent a biomarker for long‐term health.
Next‐generation sequencing of miRNAs in clinical samples of Epstein–Barr virus‐associated B‐cell lymphomas
Authors: Sakamoto Kouta , Sekizuka Tsuyoshi , Uehara Taeko , Hishima Tsunekazu , Mine Sohtaro , Fukumoto Hitomi , Sato Yuko , Hasegawa Hideki , Kuroda Makoto , Katano Harutaka
Published: February 2017

Epstein–Barr virus (EBV) encodes 49 microRNAs (miRNAs) in the BART and BHRF1 regions of its genome. Although expression profiles of EBV‐encoded miRNAs have been reported for EBV‐positive cell lines and nasopharyngeal carcinoma, to date there is little information about total miRNA expression, including cellular and viral miRNAs, in the primary tumors of EBV‐associated B‐lymphoproliferative disorders. In this study, next‐generation sequencing and quantitative real‐time reverse transcription‐PCR were used to determine the expression profiles of miRNAs in EBV‐infected cell lines and EBV‐associated B‐cell lymphomas, including AIDS‐related diffuse large B‐cell lymphoma (DLBCL), pyothorax‐associated lymphoma, methotrexate‐associated lymphoproliferative disorder, EBV‐positive DLBCL of the elderly, and Hodgkin lymphoma. Next‐generation sequencing revealed that EBV‐encoded miRNAs accounted for up to 34% of total annotated miRNAs in these cases. Expression of three miR‐BHRF1s was significantly higher in AIDS‐related DLBCL and pyothorax‐associated lymphoma compared with methotrexate‐associated lymphoproliferative disorder and EBV‐positive DLBCL of the elderly, suggesting the association of miR‐BHRF1s expression with latency III EBV infection. Heat map/clustering analysis of expression of all miRNAs, including cellular and EBV miRNAs, by next‐generation sequencing demonstrated that each EBV tumor, except methotrexate‐associated lymphoproliferative disorder, formed an isolated cluster. Principal component analysis based on the EBV‐encoded miRNA expression showed that each EBV tumor formed a distinguished cluster, but AIDS‐related DLBCL and pyothorax‐associated lymphoma formed larger clusters than other tumors. These data suggest that expression of miRNAs, including EBV‐encoded miRNAs, is associated with the tumor type and status of virus infection in these tumors.
Induction of cell death by pyropheophorbide‐α methyl ester‐mediated photodynamic therapy in lung cancer A549 cells
Authors: Tu Ping‐hua , Huang Wen‐jun , Wu Zhan‐ling , Peng Qing‐zhen , Xie Zhi‐bin , Bao Ji , Zhong Ming‐hua
Published: February 2017

Pyropheophorbide‐α methyl ester (MPPa) was a promising photosensitizer with stable chemical structure, strong absorption, higher tissue selectivity and longer activation wavelengths. The present study investigated the effect of MPPa‐mediated photodynamic treatment on lung cancer A549 cells as well as the underlying mechanisms. Cell Counting Kit‐8 was employed for cell viability assessment. Reactive oxygen species levels were determined by fluorescence microscopy and flow cytometry. Cell morphology was evaluated by Hoechst staining and transmission electron microscopy. Mitochondrial membrane potential, cellular apoptosis and cell cycle distribution were evaluated flow‐cytometrically. The protein levels of apoptotic effectors were examined by Western blot. We found that the photocytotoxicity of MPPa showed both drug‐ and light‐ dose dependent characteristics in A549 cells. Additionally, MPPa‐PDT caused cell apoptosis by reducing mitochondrial membrane potential, increasing reactive oxygen species (ROS) production, inducing caspase‐9/caspase‐3 signaling activation as well as cell cycle arrest at G0/G1 phase. These results suggested that MPPa‐PDT mainly kills cells by apoptotic mechanisms, with overt curative effects, indicating that MPPa should be considered a potent photosensitizer for lung carcinoma treatment.
Slowly on, Slowly off: Bisubstrate‐Analogue Conjugates of 5‐Iodotubercidin and Histone H3 Peptide Targeting Protein Kinase Haspin
Authors: Kestav Katrin , Viht Kaido , Konovalov Anton , Enkvist Erki , Uri Asko , Lavogina Darja
Published: February 2017

The atypical protein kinase haspin is a key player in mitosis by catalysing the phosphorylation of Thr3 in histone H3, and thus ensuring the normal function of the chromosomal passenger complex. Here, we report the development of bisubstrate‐analogue inhibitors targeting haspin. The compounds were constructed by linking 5‐iodotubercidin to the N terminus of histone H3 peptide. The new conjugates show high affinity (sub‐nanomolar KD) towards haspin as well as slow kinetics of association and dissociation (residence time of several hours). This reflects a unique binding mode and translated into improved selectivity. The latter was confirmed in a biochemical binding/displacement assay with a panel of ten protein kinases, in a thermal shift assay with off‐targets of 5‐iodotubercidin (adenosine kinase and the Cdc2‐like kinase family) and in assay with spiked HeLa cell lysate.
A novel KRAS gene mutation report in sporadic colorectal cancer, from Northwest of Iran
Authors: Dolatkhah Roya , Somi Mohammad Hossein , Kermani Iraj Asvadi , Farassati Faris , Dastgiri Saeed
Published: February 2017

Key Clinical Message

While the role of KRAS gene mutations has been widely accepted for predicting responses to anti‐EGFR therapy in patients with colorectal cancer, although this study was based on observation of a single case it gives hope that some KRAS gene mutation may have favorable prognosis. More studies are required on patients with similar mutation to validate this finding.
Anticoagulant therapy with fondaparinux in a liver transplant patient with thrombosis and liver fibrosis: a case report
Authors: Cafolla Arturo , Gentile Giuseppe
Published: February 2017

Key Clinical Message

The treatment with fondaparinux is the effective and safe anticoagulant therapy in liver transplant patient on immunosuppressive therapy with arterial thrombosis, and it seems able to reduce liver fibrosis. Although this treatment is not generalizable, further prospective large studies need to confirm this case report.
ABE Condensation over Monometallic Catalysts: Catalyst Characterization and Kinetics
Authors: Goulas Konstantinos A. , Gunbas Gorkem , Dietrich Paul J. , Sreekumar Sanil , Grippo Adam , Chen Justin P. , Gokhale Amit A. , Toste F. Dean
Published: February 2017

Herein, we present work on the catalyst development and the kinetics of acetone‐butanol‐ethanol (ABE) condensation. After examining multiple combinations of metal and basic catalysts reported in the literature, Cu supported on calcined hydrotalcites (HT) was found to be the optimal catalyst for the ABE condensation. This catalyst gave a six‐fold increase in reaction rates over previously reported catalysts. Kinetic analysis of the reaction over CuHT and HT revealed that the rate‐determining step is the C−H bond activation of alkoxides that are formed from alcohols on the Cu surface. This step is followed by the addition of the resulting aldehydes to an acetone enolate formed by deprotonation of the acetone over basic sites on the HT surface. The presence of alcohols reduces aldol condensation rates, as a result of the coverage of catalytic sites by alkoxides.
Iridium(III)‐Doped Core‐Shell Silica Nanoparticles: Near‐IR Electrogenerated Chemiluminescence in Water
Authors: Kesarkar Sagar , Rampazzo Enrico , Valenti Giovanni , Marcaccio Massimo , Bossi Alberto , Prodi Luca , Paolucci Francesco
Published: February 2017

The electrogenerated chemiluminescence (ECL) properties of two neutral cyclometalated Ir(III) complexes, Ir(iqbt)2dpm (1) and its parent complex fac‐Ir(iqbt)3 (2) [iqbt=1‐(benzo[b]thiophen‐2‐yl)‐isoquinolinate], have been investigated in acetonitrile solution. Complexes 1 and 2 display near‐infrared (near‐IR) ECL emission in acetonitrile with maxima at 712 and 706 nm, respectively. Species 1 and 2 showed a strong increase in ECL intensity upon employing benzoyl peroxide (BPO) as a co‐reactant with respect to the annihilation. The remarkable continuous ECL emission in near‐IR region makes these complexes promising candidates for development of near‐IR‐emitting Ir‐based labels in diagnostics. Furthermore, encapsulation of complex 1 within silica‐PEG nanoparticles was successfully obtained: the resulting 1@NPs are easily solubilized in aqueous media where remarkable ECL emission was observed even in aerated conditions.
Propagation of the Allosteric Modulation Induced by Sodium in the δ‐Opioid Receptor
Authors: Sun Xianqiang , Laroche Genevieve , Wang Xu , Ågren Hans , Bowman Gregory R. , Giguère Patrick M. , Tu Yaoquan
Published: February 2017

Allosteric sodium in the helix bundle of a G protein‐coupled receptor (GPCR) can modulate the receptor activation on the intracellular side. This phenomenon has confounded the GPCR community for decades. In this work, we present a theoretical model that reveals the mechanism of the allosteric modulation induced by sodium in the δ‐opioid receptor. We found that the allosteric sodium ion exploits a distinct conformation of the key residue Trp2746.48 to propagate the modulation to helices 5 and 6, which further transmits along the helices and regulates their positions on the intracellular side. This mechanism is supported by subsequent functional assays. Remarkably, our results highlight the contrast between the allosteric effects towards two GPCR partners, the G protein and β‐arrestin, as indicated by the fact that the allosteric modulation initiated by the sodium ion significantly affects the β‐arrestin recruitment, while it alters the G protein signaling only moderately. We believe that the mechanism revealed in this work can be used to explain allosteric effects initiated by sodium in other GPCRs since the allosteric sodium is highly conserved across GPCRs.
Wave and wind effects on the oxygen transfer across an air‐water interface: An experimental study
Authors: Tamburrino Aldo , Martínez Natalia
Published: February 2017

The results of an experimental study on the oxygen transfer across the air‐water interface under the combined effect of wind and mechanically generated waves are presented in the paper. The experiments were carried out in a wind tunnel containing a water tank. From the analysis of the experimental data, a relationship for determining the gas transfer coefficient was obtained, and found that the mean square slope of the water waves, the wave celerity, the wind shear velocity, and the Schmidt number are the relevant variables involved in the phenomena. The results of this study can be considered as a contribution to the advancement of the phenomenon of reaeration in closed water bodies subjected to waves and wind, such as reservoirs and lakes.
Individual and interaction effects of operating parameters on the photocatalytic degradation under visible light illumination: Response surface methodological approach
Authors: Feilizadeh Mehrzad , Rahimi Mohammad , Zakeri S. M. Esmaeil , Mahinpey Nader , Vossoughi Manouchehr , Qanbarzadeh Mojtaba
Published: February 2017

In this study, for the first time a statistical analysis based on the response surface methodology (RSM) was employed to investigate individual and interaction effects of key operating parameters of the photocatalytic degradation under visible‐light irradiation using Ag‐S/PEG/TiO2. Ag‐S/PEG/TiO2 is a visible‐light‐driven photocatalyst and was synthesized (based on earlier research) by co‐doping of TiO2 with silver and sulphur and addition of polyethylene glycol (as a reagent template). In addition, the model pollutant was methylene orange (MO) and the studied operating parameters included the photocatalyst loading, initial concentration of the pollutant, and pH of the solution. The statistics‐based experimental design and RSM was utilized to find a quadratic model as a functional relationship between the degradation efficiency and the three operating parameters. The regression analysis with R2 value of 0.9678 showed a close fit between the model prediction and experimental data of the degradation efficiency. The analysis of variance based on the model indicated that pH of the solution was the most influential factor, while the two other operating parameters were also significant. The efficiency of MO degradation reached 94.0 % under the optimum conditions (i.e. photocatalyst loading of 1.20 g/L, MO concentration of 5 mg/L, and pH of 2).
High cancer drug prices 4 years later—Progress and prospects
Authors: Kantarjian Hagop , Patel Yogin
Published: February 2017

High cancer drug prices continue to be a significant problem in the United States despite the existence of remedial solutions that can be readily implemented with appropriate legislation.

See also pages 1313‐23.
Improving access to high‐cost cancer drugs in Latin America: Much to be done
Authors: Ruiz Rossana , Strasser‐Weippl Kathrin , Touya Diego , Herrero Vincent Carmen , Hernandez‐Blanquisett Abraham , St. Louis Jessica , Bukowski Alexandra , Goss Paul E.
Published: February 2017

Lack of access to high‐cost medications is a complex issue at the intersection of economics, medicine, politics, and ethics, and it poses a significant threat to global health care. The problem is even more significant in low‐ and middle‐income countries, such as those in Latin America, where governments and individuals struggle to pay for products that are priced at several times the level of their per capita gross domestic product. In this review, we examine the determinants for increasing drug costs and how Latin American countries face this burgeoning crisis. We emphasize that a number of opportunities and strategies to reduce costs and improve access exist and should be identified and implemented, ideally within a regional approach with multiple stakeholders involved and based on systematic and transparent cost‐effectiveness analyses. Cancer 2017;123:1313–1323. © 2016 American Cancer Society.
Artificial intelligence (AI) systems for interpreting complex medical datasets
Authors: Altman RB
Published: February 2017

Advances in machine intelligence have created powerful capabilities in algorithms that find hidden patterns in data, classify objects based on their measured characteristics, and associate similar patients/diseases/drugs based on common features. However, artificial intelligence (AI) applications in medical data have several technical challenges: complex and heterogeneous datasets, noisy medical datasets, and explaining their output to users. There are also social challenges related to intellectual property, data provenance, regulatory issues, economics, and liability.
Translation and Clinical Development of Bispecific T‐cell Engaging Antibodies for Cancer Treatment
Authors: Yuraszeck T , Kasichayanula S , Benjamin JE
Published: February 2017

Bispecific T‐cell Engagers (BiTE®) antibody constructs enable a polyclonal T‐cell response to cell‐surface tumor‐associated antigens, bypassing the narrow specificities of T‐cell receptors and the need for antigen presentation through the major histocompatibility complex pathways. Blinatumomab, a CD19xCD3 BiTE® antibody construct, received accelerated approval for the treatment of relapsed/refractory Philadelphia chromosome negative acute lymphoblastic leukemia. Herein we review the pharmacology, safety, and efficacy observed in studies of blinatumomab and other BiTE® antibody constructs. Quantitative systems pharmacology is envisioned as a means to optimize dosing decisions for trials in which BiTE® antibody constructs are administered as monotherapy or in combination with other immunotherapies.
Essential Medicines for Children
Authors: Hoppu K
Published: February 2017

The World Health Organization (WHO) defines Essential Medicines as those that satisfy the priority healthcare needs of the population. The right to essential medicines has been considered an important component of the right to health. In the name of equity, children should also have access to appropriate, available, affordable, and quality essential medicines they need, but children's essential medicines are too often missing.
Occlusal features and need for orthodontic treatment in persons with osteogenesis imperfecta
Authors: Nguyen Minh Son , Binh Ho Duy , Nguyen Khac Minh , Maasalu Katre , Kõks Sulev , Märtson Aare , Saag Mare , Jagomägi Triin
Published: February 2017

The aim of the study was to (a) analyse dental occlusion and determine the need for orthodontic treatment of persons with osteogenesis imperfecta (OI) in comparison with the healthy population and (b) investigate the associations between OI and malocclusion. A case‐control study included 26 OI persons and 400 healthy participants (control group). Occlusal features and the need for orthodontic treatment were defined according to Dental Health Component‐Index of Orthodontic Treatment Need and Dental Aesthetic Index. Results showed that Angle Class I, II, and III relationship was found in 23.1%, 3.8%, and 73.1% of OI group, and in the control group, it was 67%, 17.5%, and 15.5%, respectively. OI group had significantly higher prevalence of reverse overjet >1 mm (76.9%), missing teeth (42.3%), posterior crossbite (34.6%), and open bite >2 mm (19.2%) compared to the control group (8.5%, 2.2%, 6.2%, and 3.5%, respectively). OI group had less incisal segment crowding and more incisal segment spacing than the control group (p < 0.05). The need for orthodontic treatment of OI group according to Dental Health Component‐Index of Orthodontic Treatment Need and Dental Aesthetic Index was 88.5% and 61.5%, respectively, while in the control group, it was 24.8% and 51.8%. The malocclusion in OI persons was associated with reverse overjet > 1 mm (OR = 13.3, 95% CI = 3.9–44.7, p < .001), Angle Class III malocclusion (OR = 8.0, 95% CI = 2.0–30.8, p = .003), and missing teeth (OR = 4.7, 95% CI = 1.0–22.4, p = .049). In conclusion, there is the high probability of malocclusion in OI persons. Persons with OI require early orthodontic treatment because of significant correlation of OI disease with Angle Class III malocclusion, reverse overjet, and missing teeth.
Electrophysiological evidence of altered visual processing in adults who experienced visual deprivation during infancy
Authors: Segalowitz Sidney J. , Sternin Avital , Lewis Terri L. , Dywan Jane , Maurer Daphne
Published: February 2017

We examined the role of early visual input in visual system development by testing adults who had been born with dense bilateral cataracts that blocked all patterned visual input during infancy until the cataractous lenses were removed surgically and the eyes fitted with compensatory contact lenses. Patients viewed checkerboards and textures to explore early processing regions (V1, V2), Glass patterns to examine global form processing (V4), and moving stimuli to explore global motion processing (V5). Patients' ERPs differed from those of controls in that (1) the V1 component was much smaller for all but the simplest stimuli and (2) extrastriate components did not differentiate amongst texture stimuli, Glass patterns, or motion stimuli. The results indicate that early visual deprivation contributes to permanent abnormalities at early and mid levels of visual processing, consistent with enduring behavioral deficits in the ability to process complex textures, global form, and global motion.
The development of repetitive motor behaviors in deer mice: Effects of environmental enrichment, repeated testing, and differential mediation by indirect basal ganglia pathway activation
Authors: Bechard Allison R. , Bliznyuk Nikolay , Lewis Mark H.
Published: February 2017

Little is known about the mechanisms mediating the development of repetitive behaviors in human or animals. Deer mice reared with environmental enrichment (EE) exhibit fewer repetitive behaviors and greater indirect basal ganglia pathway activation as adults than those reared in standard cages. The developmental progression of these behavioral and neural circuitry changes has not been characterized. We assessed the development of repetitive behavior in deer mice using both a longitudinal and cohort design. Repeated testing negated the expected effect of EE, but cohort analyses showed that progression of repetitive behavior was arrested after 1 week of EE and differed significantly from controls after 3 weeks. Moreover, EE reductions in repetitive behavior were associated with increasing activation of indirect pathway nuclei in males across adolescence, but not females. These findings provide the first assessment of developmental trajectories within EE and support indirect pathway mediation of repetitive behavior in male deer mice.
Variable effects of climate on forest growth in relation to climate extremes, disturbance, and forest dynamics
Authors: Itter Malcolm S. , Finley Andrew O. , D'Amato Anthony W. , Foster Jane R. , Bradford John B.
Published: February 2017

Changes in the frequency, duration, and severity of climate extremes are forecast to occur under global climate change. The impacts of climate extremes on forest productivity and health remain difficult to predict due to potential interactions with disturbance events and forest dynamics—changes in forest stand composition, density, size and age structure over time. Such interactions may lead to non‐linear forest growth responses to climate involving thresholds and lag effects. Understanding how forest dynamics influence growth responses to climate is particularly important given stand structure and composition can be modified through management to increase forest resistance and resilience to climate change. To inform such adaptive management, we develop a hierarchical Bayesian state space model in which climate effects on tree growth are allowed to vary over time and in relation to past climate extremes, disturbance events, and forest dynamics. The model is an important step toward integrating disturbance and forest dynamics into predictions of forest growth responses to climate extremes. We apply the model to a dendrochronology data set from forest stands of varying composition, structure, and development stage in northeastern Minnesota that have experienced extreme climate years and forest tent caterpillar defoliation events. Mean forest growth was most sensitive to water balance variables representing climatic water deficit. Forest growth responses to water deficit were partitioned into responses driven by climatic threshold exceedances and interactions with insect defoliation. Forest growth was both resistant and resilient to climate extremes with the majority of forest growth responses occurring after multiple climatic threshold exceedances across seasons and years. Interactions between climate and disturbance were observed in a subset of years with insect defoliation increasing forest growth sensitivity to water availability. Forest growth was particularly sensitive to climate extremes during periods of high stem density following major regeneration events when average inter‐tree competition was high. Results suggest the resistance and resilience of forest growth to climate extremes can be increased through management steps such as thinning to reduce competition during early stages of stand development and small‐group selection harvests to maintain forest structures characteristic of older, mature stands.
Coupled geomorphic and habitat response to a flood pulse revealed by remote sensing
Authors: Harrison Lee R. , Pike Andrew , Boughton David A.
Published: February 2017

Despite a growing consensus on the importance of floods in structuring river ecosystems, predicting the geomorphic and habitat response to specific flood pulses across a range of scales remains challenging. We used a large reservoir release in a semiarid river to characterize geomorphic and habitat responses to a flood pulse, using an integrated field, remote sensing, and modeling approach. Large‐scale geomorphic changes were observed as a result of the flood, including lateral migration of the river channel, gravel bar formation, and development of off‐channel chutes. Spatial patterns of gravel storage varied with downstream distance from a large dam, with the upper 15 km experiencing a net sediment deficit and the lower 65 km undergoing net deposition. The longitudinal trends in gravel transport and storage reflected differences in channel gradient and predicted values of sediment mobility. The flood lowered the channel by an average of −0.5 m and roughly doubled the areal extent of pools, by incising new pools in curved reaches and in areas where the river abutted valley walls and terraces. The increased pool abundance provided greater habitat connectivity and was predicted to have positive impacts on anadromous steelhead, providing up to a 3‐fold increase in the number of juvenile fish the river could support. Results from this study highlight the value of using flood pulses as opportunities to learn about river behavior, and for testing the degree to which physical processes can help restore the form and function of river ecosystems.
Olefin‐Bond Chemodifferentiation through Cross‐Metathesis Reactions: A Stereocontrolled Approach to Functionalized β2,3‐Amino Acid Derivatives
Authors: Kardos Márton , Kiss Loránd , Haukka Matti , Fustero Santos , Fülöp Ferenc
Published: February 2017

Substituted cyclopentanes or tetrahydrofurans bearing two vinyl groups have been investigated in cross‐metathesis reactions to explore chemodiscrimination of the two olefin bonds. The syntheses consisted of ring opening of constrained unsaturated β‐lactams or bicyclic β‐amino acids, followed by cross‐metathesis to test the chemodifferentiation of the divinyl‐substituted azetidinones or β‐amino esters in the presence of various ruthenium‐based catalysts.
Plasma Modified V2O5/PEDOT Hybrid Based Flexible Electrochromic Devices
Authors: Karaca Gozde Yurdabak , Eren Esin , Alver Ceyda , Koc Umran , Uygun Emre , Oksuz Lutfi , Oksuz Aysegul Uygun
Published: February 2017

Vanadium oxide/poly (3,4‐ ethylenedioxythiophene)(V2O5‐PEDOT) hybrid materials were prepared in a rotating quartz plasma reactor via capacitively coupled radio frequency (RF 13.56 MHz) plasma. Thin films of V2O5‐PEDOT hybrid and V2O5 were obtained by electron beam evaporation technique onto flexible PET substrate for electrochromic devices (ECDs) applications. As a counter electrode, both RF magnetron sputtered MoO3 onto ITO coated PET and only ITO coated PET electrodes were used. Characterizations of the films were carried out via using scanning electron microscopy‐energy dispersive X‐ray spectroscopy (SEM‐EDX) and X‐ray diffraction (XRD). Hybrid ECDs results showed that synergistic effect depending on improved stability between V2O5 and PEDOT. As a result, we developed all solid complementary electrochromic devices including V2O5, V2O5‐PEDOT and MoO3 films. The electrochromic device characteristics such as electrochromic contrast, coloration efficiency, switching time were calculated from optical and electrochemical measurements. The highest coloration efficiency and optical contrast were obtained as 53 cm2/C and 17 % for V2O5‐PEDOT/MoO3‐based ECD.