bluuebunny/crossref_metadata_2025 huggingface dataset:
Catalytic Mechanism of the Hotdog‐Fold Thioesterase PA1618 Revealed by X‐ray Structure Determination of a Substrate‐Bound Oxygen Ester Analogue Complex
Authors: Latham John A. , Ji Tianyang , Matthews Kaila , Mariano Patrick S. , Allen Karen N. , Dunaway‐Mariano Debra
Published: July 2017

Thioesterase activity accounts for the majority of the activities in the hotdog‐fold superfamily. The structures and mechanisms of catalysis for many hotdog enzymes have been elucidated by X‐ray crystallography and kinetics to probe the specific substrate usage and cellular functions. However, structures of hotdog thioesterases in complexes with substrate analogues reported to date utilize ligands that either represent truncations of the substrate or include additional atoms to prevent hydrolysis. Here we present the synthesis of an isosteric and isoelectronic substrate analogue—benzoyl‐OdCoA—and the X‐ray crystal structure of a complex of the analogue with Pseudomonas aeruginosa hotdog thioesterase PA1618 (at 1.72 Å resolution). The complex is compared with that of the “imperfect” substrate analogue phenacyl‐CoA, refined to a resolution of 1.62 Å. Kinetic and structural results are consistent with Glu64 as the catalytic residue and with the involvement of Gln49 in stabilization of the transition state. Structural comparison of the two ligand‐bound structures revealed a crucial ordered water molecule coordinated in the active site of the benzoyl‐OdCoA structure but not present in the phenacyl‐CoA‐bound structure. This suggests a general base mechanism of catalysis in which Glu64 activates the coordinated water nucleophile. Together, our findings reveal the importance of a closely similar substrate analogue to determine the true substrate binding and catalytic mechanism.
Intrauterine exposure to oestradiol promotes sex‐specific differential effects on the prostatic development of neonate gerbils
Authors: Sanches Bruno D. A. , Maldarine Juliana S. , Biancardi Manoel F. , Santos Fernanda C. A. , Pinto‐Fochi Maria E. , Antoniassi Julia Q. , Góes Rejane M. , Vilamaior Patrícia S. L. , Taboga Sebastião R.
Published: July 2017

The effects of intrauterine exposure to 17β‐oestradiol (E2) are well studied for the male prostate and there are accumulating evidences that the exposure to high dosages leads to a hypomorphic development. However, there is a lack of information about the effects of intrauterine exposure to E2 in the prostate of rodent females, and such research becomes relevant in view of the presence of functional prostate in a proportion of women, and the morphophysiological similarities between the prostate of female rodents and the prostate of women. This study uses histochemical, immunohistochemical, immunofluorescence and three‐dimensional (3D) reconstruction techniques to evaluate the effects of intrauterine exposure to E2 (500 BW/d) on neonatal prostate development in both male and female gerbils. It was verified that intrauterine exposure to E2 promotes epithelial proliferation and growth of prostatic budding in females, whereas in males the prostatic budding shows hypomorphic growth in the VMP (Ventral Mesenchymal Pad) as well as reduced epithelial proliferation. Together, the data demonstrate that intrauterine exposure to E2 causes different effects on male and female prostates of the gerbil even at the early postnatal development of the gland.
Only 1 in 4 teens/young adults with OUDs get naltrexone or buprenorphine: Study
Authors: Knopf Alison
Published: July 2017

While buprenorphine and naltrexone are both used for adolescents and young adults with opioid use disorder (OUD), the extent of such use has not been studied on a national basis, until the publication in JAMA Pediatrics in July of a study by Scott E. Hadland, M.D., and colleagues.
Neuropsychiatric outcomes of extreme prematurity on 11‐year‐olds
Authors: Knopf Alison
Published: July 2017

This is the first study on prematurity and outcomes in adolescence, conducted by Swedish researchers and published in Pediatrics in 2007. The second study, published in February in Pediatrics, with the same author (Aijaz Farooqi, M.D., Ph.D., and colleagues), shows the relevance of the conclusions: that there is a preterm behavioral phenotype that can be seen in adolescents (see p. 1, bottom lead). The third, published in July in Pediatrics and focusing on behavioral issues in the teens, will be examined in next month's issue of CABL. The studies are important because they support the same concept: that prematurity can denote a phenotype with sequelae in adolescence which could be prevented or reduced.
First patient with hereditary spastic paraplegia type 8 in Poland
Authors: Bogucki Piotr , Sobczyńska‐Tomaszewska Agnieszka
Published: July 2017

Key Clinical Message

SPG 8 is an autosomal dominant HSP, which phenotype results from KIAA0196 gene mutations. There have been twelve types of KIAA0196 mutations described in HGMD, which are located in conservative region of gene encoding strumpellin. We describe first patient in Poland, simultaneously second in the world with KIAA0196 mutation – p.V620A.
Silver‐Doped Cobalt (Magnesium) Aluminum Mixed Metal Oxides as Potential Catalysts for Nitrous Oxide Decomposition
Authors: Jabłońska Eng. Magdalena , Buselli Lorenzo , Nocuń Eng. Marek , Palkovits Regina
Published: July 2017

N2O is a potent greenhouse gas released among others in nitric and adipic acid production as well as from stationary and mobile combustion sources. A catalytic decomposition is highly attractive but requires catalysts active over a broad temperature range and in the presence of inhibiting compounds such as NO and O2. Ag‐doped Co‐(Mg)‐Al‐Ox mixed metal oxides obtained by the coprecipitation of metal nitrate precursors followed by calcination were evaluated as potential catalysts for N2O decomposition (deN2O) also in the presence of NO and/or O2. Ag integration during synthesis proved to be essential for superior catalytic activity. The catalyst with the optimum composition, AgCo3Al‐Ox (Co/Al=3:1 mol %, 1.0 wt % Ag), achieved full N2O conversion at 350 and 450 °C under N2O/N2 and N2O/NO/O2/N2 conditions, respectively. Catalyst characterization, with a focus on H2 temperature‐programmed reduction and X‐ray photoelectron spectroscopy, evidenced that abundant Ag0 on the surface of (1.0–2.8 wt %)AgCo3Al‐Ox enhanced the reduction of cobalt spinels to enable the superior catalytic performance.
Mesoporous Ni(OH)2/CeNixOy Composites Derived Ni/CeNixOy Catalysts for Dry Reforming of Methane
Authors: Dou Jian , Bao Zhenghong , Yu Fei
Published: July 2017

Designing stable nickel‐based catalysts is critical for dry reforming of methane with carbon dioxide (DRM) to produce fuels and chemicals. Herein, mesoporous Ni(OH)2/CeNixOy composites were prepared by a one‐pot hydrothermal synthetic route. Aggregation of Ni(OH)2 nanoplates and CeNixOy nanocrystals generates mesopores from the void space and creates a surface area as high as 138 m2 g−1. With the Ni content in the range of 0.7–12.5 %, the mesoporous structure is stable after reduction with the highest surface area as 94 m2 g−1. Reduction of Ni(OH)2/CeNixOy composites at 500 °C converts Ni(OH)2 nanoplates into Ni nanoparticles. The size of the reduced Ni nanoparticles was controlled from 10 to 140 nm by adjusting the Ni loading from 0.7 to 42.7 %. The catalysts with Ni/(Ni+Ce) ratios of 0.4 and 0.5, 0.4 Ni/CeNixOy and 0.5 Ni/CeNixOy, respectively, exhibit enhanced catalytic performance for DRM reaction with their activities 3–5 times as high as those of 0.6 Ni/CeNixOy and 0.8 Ni/CeNixOy catalysts, owing to the good dispersion of 10 nm Ni nanoparticles within mesoporous CeNixOy. Furthermore, the 0.5 Ni/CeNixOy catalyst is very stable for DRM for 140 h. The robust stability of 0.5 Ni/CeNixOy catalyst possibly stems from the strong interactions between Ni nanoparticles and the CeNixOy surface, which stabilize Ni nanoparticles during DRM reaction.
Two‐Step Deposition/Reduction Synthesis of Porous Lamellar β‐Ni(OH)2/Reduced Graphene Oxide Composites with Large Capacitance for Supercapacitors
Authors: Yuan Shuxia , Lu Chunxiang , Li Ying , Wang Xiaomin
Published: July 2017

Ni(OH)2/RGO composite are synthesized though a facile two‐step method, in which the Ni(OH)2 deposition and GO reduction processes take place separately. The present methods promote the deposition of more Ni(OH)2 and full utilization of RGO, owing to the high reactivity, good solubility, and dispersity of GO. Moreover, the utilization of additives is avoided. The Ni(OH)2/RGO synthesized by using the two‐step method shows a uniform porous lamellar structure with a high specific surface area. When employed as a supercapacitor electrode material, the Ni(OH)2/RGO composite exhibits a high specific capacitance of 2877 F g−1, long cycle life with capacitance retention of 86.5 % after 4000 cycles, and high energy density of 120.9 Wh kg−1 at a power density of 0.14 kW kg−1. The Ni(OH)2/RGO composite prepared by using the two‐step method in this work shows 11.8–85.1 % higher specific capacitances than composites fabricated by using the other method. The excellent performances and the facile synthesis method highlight the promising potential of the present Ni(OH)2/RGO composite in supercapacitor applications.
Light‐Controlled Photochemical Synthesis of Gelatin‐Capped Gold Nanoparticles for Spectral Activity and Electro‐oxidation of Quercetin
Authors: Thirumalraj Balamurugan , Rajkumar Chellakannu , Chen Shen‐Ming , Dhenadhayalan Namasivayam , Lin King‐Chuen
Published: July 2017

Gelatin‐capped gold nanoparticles (GEL‐AuNPs) were prepared through the in situ reduction of tetrachloroauric acid (HAuCl4) in gelatin solution under UV light without external reducing agents. The effect of HAuCl4 concentration and reaction time intervals were monitored by using UV/Vis spectroscopy. The hydrophilic and biocompatible nature of the GEL‐AuNPs composite was studied in terms of their optical activity and electrocatalytic activity toward quercetin (QR). The optical spectra showed a decrease in the absorbance and enhancement in fluorescence of QR as a function of AuNPs, owing to the interaction between QR and GEL‐AuNPs. The spectral changes of QR may be caused by hydrogen‐bond formation between the amine groups in GEL‐AuNPs and −OH and/or carbonyl groups in QR. In addition, the GEL‐AuNPs exhibited excellent electrocatalytic activity towards QR oxidation. The DPV results displayed a good linear response range over the concentrations of QR (0.02 to 34.5 μM) with a detection limit of 1.9 nM. Moreover, GEL‐AuNPs could be utilized for the determination of QR in onion and apple samples for practical applications with satisfactory recoveries.
Stepwise Growth of Fullerene Nanoparticles through Guest Exchange of γ‐Cyclodextrin Complexes in Water
Authors: Sugikawa Kouta , Kozawa Kentaro , Ueda Masafumi , Ikeda Atsushi
Published: July 2017

Stepwise growth of fullerene nanoparticles (nCx; x=60 or 70) was performed through guest exchange of a γ‐cyclodextrin (γ‐CD) complex. Fullerenes bicapped by γ‐CD were mixed with presynthesized nCx in the presence of poly(ethylene glycol) (PEG) in water. Fullerenes expelled from the γ‐CD hosts by PEG were piled on the original nCx, resulting in growth of nCx. This process could be repeated and the size of nCx increased according to the number of growth steps. The growth of fullerene nanoparticles was confirmed by UV/Vis absorption spectroscopy, dynamic light scattering measurements, and TEM observations. The stepwise growth method also enabled the preparation of C60/C70 core/shell fullerene nanoparticles, which had the ability to photogenerate active oxygen, 1O2.
Prediction of EPR Spectra of Lyotropic Liquid Crystals using a Combination of Molecular Dynamics Simulations and the Model‐Free Approach
Authors: Prior Christopher , Oganesyan Vasily S.
Published: July 2017

We report the first application of fully atomistic molecular dynamics (MD) simulations to the prediction of the motional electron paramagnetic resonance (EPR) spectra of lyotropic liquid crystals in different aggregation states doped with a paramagnetic spin probe. The purpose of this study is twofold. First, given that EPR spectra are highly sensitive to the motions and order of the spin probes doped within lyotropic aggregates, simulation of EPR line shapes from the results of MD modelling provides an ultimate test bed for the force fields currently employed to model such systems. Second, the EPR line shapes are simulated using the motional parameters extracted from MD trajectories using the Model‐Free (MF) approach. Thus a combined MD‐EPR methodology allowed us to test directly the validity of the application of the MF approach to systems with multi‐component molecular motions. All‐atom MD simulations using the General AMBER Force Field (GAFF) have been performed on sodium dodecyl sulfate (SDS) and dodecyltrimethylammonium chloride (DTAC) liquid crystals. The resulting MD trajectories were used to predict and interpret the EPR spectra of pre‐micellar, micellar, rod and lamellar aggregates. The predicted EPR spectra demonstrate good agreement with most of experimental line shapes thus confirming the validity of both the force fields employed and the MF approach for the studied systems. At the same time simulation results confirm that GAFF tends to overestimate the packing and the order of the carbonyl chains of the surfactant molecules.
A Series of Linear {FeIII2FeII} Complexes with Paramagnetic Building‐Block‐Modified Spin Crossover Behaviors
Authors: Hu Ji‐Xiang , Meng Yin‐Shan , Zhao Liang , Zhu Hai‐Lang , Liu Lei , Liu Qiang , Jiao Cheng‐Qi , Liu Tao
Published: July 2017

Tuning of the spin crossover (SCO) behavior through paramagnetic building blocks with different steric hindrance effects is of great interest in terms of the synergy between SCO and magnetic interactions. Herein, the steric effect of specified FeIII building blocks is modified, from the large Tp* (hydridotris(3,5‐dimethylpyrazol‐1‐yl)borate) analogue to a small Tp (hydrotris(pyrazolyl)borate) derivative; the FeII SCO unit and FeIII paramagnetic ions are incorporated into three well isolated trinuclear complexes featuring thermally induced and light‐induced SCO properties. Reanalysis of the structures reveals that π–π stacking interactions play a key role in the thermal hysteresis and anomalous octahedral distortion parameter Σ around the FeII ion. The Tp* ligand showing the largest steric hindrance induces elongated FeII−N bond lengths and bending of the C≡N−FeII angle in 1, as well as having a relatively large electron donor effect, which leads to the lowest thermal transition temperature among the three compounds.
Gemini Surfactants Templated Mesoporous Silica Microparticles: from Solid to Hollow Mesoporous Spheres
Authors: Li Min , Zhang Chun , Yang Xiangliang
Published: July 2017

We synthesized a series of mesoporous silica microparticles (MSs) using cationic gemini surfactants C14–2‐n (n = 2, 6, 10, 14) as templates. The porous structures and pore size of these MSs can be tuned by varying the length of alkyl chain in gemini surfactant templates. These MSs showed effective doxorubicin (DOX) loading and a pH‐responsive drug release characteristics. These results indicate that the MSs, especially the hollow mesoporous silica nanoparticles, have great potential for biomedical applications.
Regio‐ and (E)‐Stereoselective Triborylation of Propargylic Carbonates
Authors: Yang Zheng , Cao Tao , Han Yulin , Lin Weilong , Liu Qi , Tang Yang , Zhai Yizhan , Jia Minqiang , Zhang Wanli , Zhu Tonghao , Ma Shengming
Published: July 2017

An efficient synthesis of (E)‐alken‐1,2,3‐triboronates form readily available propargylic carbonates is described. The reaction enjoys excellent regio‐ and E‐selectivity and many synthetically useful functional groups can be tolerated. Based on mechanistic studies, a two‐step mechanism via 1,2‐allenyl boronate intermediate is proposed.
Discovery of Novel Potent Muscarinic M3 Receptor Antagonists with Proper Plasma Stability by Structural Recombination of Marketed M3 Antagonists
Authors: Xiang Zuojuan , Liu Jun , Sun Hongbin , Wen Xiaoan
Published: July 2017

The marketed long‐acting M3 antagonists for treatment of chronic obstructive pulmonary disease have inappropriate plasma stability (either overstable or excessively unstable), which causes substantial systemic exposure or poor patient compliance. To discover novel M3 antagonists with proper plasma stability, we synthesized and biologically evaluated a series of chiral quaternary ammonium salts of pyrrolidinol esters, which were designed by structural recombination of the marketed M3 antagonists. As a result, two novel potent M3 antagonists, (R/S)‐3‐[2‐hydroxy‐2,2‐di(thiophen‐2‐yl)acetoxy]‐1,1‐dimethylpyrrolidinium bromides (1 a: Ki=0.16 nm, IC50=0.38 nm, t1/2=9.34 min; 1 b: Ki=0.32 nm, IC50=1.01 nm, t1/2=19.2 min) with proper plasma stability were identified, which (particularly 1 a) hold great promise as clinical drug candidates to overcome the drawbacks caused by the inappropriate stability of the currently marketed M3 antagonists. In addition, structure–activity relationship studies revealed that the R configuration of the pyrrolidinyl C3 atom was clearly better than the S configuration.
Prognostic factors and survival outcomes in patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era: Cohort study of 477 patients
Authors: Jain Preetesh , Kantarjian Hagop M. , Ghorab Ahmad , Sasaki Koji , Jabbour Elias J. , Nogueras Gonzalez Graciela , Kanagal‐Shamanna Rashmi , Issa Ghayas C. , Garcia‐Manero Guillermo , KC Devendra , Dellasala Sara , Pierce Sherry , Konopleva Marina , Wierda William G. , Verstovsek Srdan , Daver Naval G. , Kadia Tapan M. , Borthakur Gautam , O'Brien Susan , Estrov Zeev , Ravandi Farhad , Cortes Jorge E.
Published: July 2017

BACKGROUND

Outcomes in patients with chronic myeloid leukemia in blast phase (CML‐BP) are historically dismal. Herein, the authors sought to analyze the characteristics, prognostic factors, and survival outcomes in patients with CML‐BP in the tyrosine kinase inhibitor (TKI) era.

METHODS

A total of 477 patients with CML‐BP were treated with a TKI at some point during the course of their CML. Cox proportional hazard models identified characteristics that were predictive of survival. Overall survival and failure‐free survival were assessed. Optimal cutoff points for specific parameters were identified using classification and regression tree (CART) analysis.

RESULTS

The median age of the patients was 53 years (range, 16‐84 years) and 64% were male. Approximately 80% of patients initially were diagnosed in the chronic phase of CML at a median of 41 months (range, 0.7‐298 months) before transformation to CML‐BP. De novo CML‐BP occurred in 71 patients. Approximately 72% of patients received TKI therapy before CML‐BP. The initial therapy for CML‐BP included a TKI alone (35%), a TKI with chemotherapy (46%), and non‐TKI therapies (19%). The median overall survival was 12 months and the median failure‐free survival was 5 months. In multivariate analysis, myeloid immunophenotype, prior TKI, age ≥58 years, lactate dehydrogenase level ≥1227 IU/L, platelet count < 102 K/μL, no history of stem cell transplantation, transition to BP from chronic phase/accelerated phase, and the presence of chromosome 15 aberrations predicted for a significantly increased risk of death. Achievement of major hematologic response and/or complete cytogenetic response to first‐line treatment was found to be predictive of better survival. The combination of a TKI with intensive chemotherapy followed by stem cell transplantation appeared to confer the best outcome.

CONCLUSIONS

Patients with CML‐BP continue to pose a therapeutic challenge, have dismal outcomes, and require newer treatment approaches. Cancer 2017;123:4391‐402. © 2017 American Cancer Society.
Pseudocapacitive Desalination of Brackish Water and Seawater with Vanadium‐Pentoxide‐Decorated Multiwalled Carbon Nanotubes
Authors: Lee Juhan , Srimuk Pattarachai , Aristizabal Katherine , Kim Choonsoo , Choudhury Soumyadip , Nah Yoon‐Chae , Mücklich Frank , Presser Volker
Published: July 2017

A hybrid membrane pseudocapacitive deionization (MPDI) system consisting of a hydrated vanadium pentoxide (hV2O5)‐decorated multi‐walled carbon nanotube (MWCNT) electrode and one activated carbon electrode enables sodium ions to be removed by pseudocapacitive intercalation with the MWCNT–hV2O5 electrode and chloride ion to be removed by non‐faradaic electrosorption of the porous carbon electrode. The MWCNT–hV2O5 electrode was synthesized by electrochemical deposition of hydrated vanadium pentoxide on the MWCNT paper. The stable electrochemical operating window for the MWCNT–hV2O5 electrode was between −0.5 V and +0.4 V versus Ag/AgCl, which provided a specific capacity of 44 mAh g−1 (corresponding with 244 F g−1) in aqueous 1 m NaCl. The desalination performance of the MPDI system was investigated in aqueous 200 mm NaCl (brackish water) and 600 mm NaCl (seawater) solutions. With the aid of an anion and a cation exchange membrane, the MPDI hybrid cell was operated from −0.4 to +0.8 V cell voltage without crossing the reduction and oxidation potential limit of both electrodes. For the 600 mm NaCl solution, the NaCl salt adsorption capacity of the cell was 23.6±2.2 mg g−1, which is equivalent to 35.7±3.3 mg g−1 normalized to the mass of the MWCNT–hV2O5 electrode. Additionally, we propose a normalization method for the electrode material with faradaic reactions based on sodium uptake capacities.
If the coping fits, use it: Preadolescent recent stress exposure differentially predicts post‐TSST salivary cortisol recovery
Authors: Bendezú Jason J. , Wadsworth Martha E.
Published: July 2017

This study examined recent stress exposure and effortful coping effects on salivary cortisol (sC) response patterns in preadolescent boys and girls (N = 121, Mage = 10.60 years). Children were exposed to the Trier Social Stress Test (TSST) and one of two randomly assigned, post‐TSST coping conditions: distraction and avoidance. Piecewise growth multilevel modeling did not link children's recent stressful life events or hair cortisol (hC) levels to sC reactivity, though each interacted with coping condition to predict sC recovery patterns. Children with elevated life stressor and hC levels demonstrated protracted sC recovery when primed with distraction, yet more efficient sC recovery when primed with avoidance. Findings challenge assumptions about universally “good” and “bad” coping by highlighting contexts where each succeed and fail in helping children manage acute stress physiology.
Three decades of forest harvesting along a suburban–rural continuum
Authors: Kittredge David B. , Thompson Jonathan R. , Morreale Luca L. , Short Gianotti Anne G. , Hutyra Lucy R.
Published: July 2017

Timber harvest is an important ecological disturbance that influences species composition, understory conditions, stand structure and growth, and carbon dynamics. Regional variation in harvest regimes and the associated ecological consequences are linked to social and biophysical attributes of the landscape. We analyzed three decades of change in commercial timber harvesting on all private and public forest throughout 328 towns in Massachusetts (USA). We quantified changes in harvest activity over time and estimated probability of harvest occurrence and proportion of a town's harvest as functions of biophysical and social settings. We found little evidence of any temporal trends in harvest activity at the state or town scale. Across the suburban–rural interface, the probability of harvest occurrence on private land was consistently a function of the proportion of a town's land in forest and the distance to the urban center (Boston). The proportion of private land in a town subject to harvest was negatively related to a town's median household income. There was a significant difference in the proportion of private forest harvested in suburban vs. rural towns. The proportion of public forest subject to harvests was not related to any of the variables we examined. Total statewide estimates of commercial timber that fail to account for the suburban–rural transition may overestimate available or potential volume. Ecologically, the timber harvest disturbance regime in landscapes dominated by private ownership is strongly influenced by socioeconomic factors such as affluence and proximity to urban development, unlike other forms of natural disturbance typical of the region (e.g., wind).
A prospective evaluation of the established criteria for heart failure with preserved ejection fraction using the Alberta HEART cohort
Authors: Ezekowitz Justin A. , McAlister Finlay A. , Howlett Jonathan , Alemayehu Wendimagegn , Paterson Ian , Belenkie Israel , Oudit Gavin Y. , Kaul Padma , Dyck Jason R. , Anderson Todd ,   on behalf of the Alberta HEART Investigators
Published: July 2017

Aims

Heart failure with a preserved ejection fraction (HF‐PEF) remains a difficult clinical diagnosis. The aim of this study was to test the utility of established criteria to classify patients with HF‐PEF. We prospectively enrolled patients into one of five groups across a spectrum of cardiac disease and applied three different criteria for HF‐PEF and calculated diagnostic metrics.

Methods and results

A total of 565 patients were included in the analysis, including 170 patients with an adjudicated diagnosis of HF‐PEF, 152 patients with heart failure with reduced ejection fraction, 152 patients at risk for heart failure, and 91 age‐matched healthy controls. For the diagnosis of HF‐PEF, the positive likelihood ratios were 6.1, 6.9, and 4.8 for the Zile, European Society of Cardiology (ESC) 2007, and ESC 2016 criteria, respectively. The negative likelihood ratios were 0.58, 0.60, and 0.42 for the Zile, ESC 2007, and ESC 2016 criteria, respectively. All three criteria lacked sensitivity to detect HF‐PEF (46.5%, 44.1%, and 51.8%, respectively) but were highly specific (92.4%, 93.9%, and 89%, respectively). We further evaluated the criteria to distinguish HF‐PEF from other diagnoses after excluding heart failure with reduced ejection fraction; the results were similar.

Conclusions

In this community based cohort, the likelihood ratios of the existing criteria for HF‐PEF were not at the level necessary to be considered diagnostic. Improved criteria for the diagnosis of patients with HF‐PEF are needed.
Role of CD4 T cell helper subsets in immune response and deviation of CD8 T cells in mice*
Authors: Hogg Alison , Sui Yongjun , Ben‐Sasson Shlomo Z. , Paul William E. , Berzofsky Jay A.
Published: July 2017

The ability of different CD4+ T cell subsets to help CD8+ T‐cell response is not fully understood. Here, we found using the murine system that Th17 cells induced by IL‐1β, unlike Th1, were not effective helpers for antiviral CD8 responses as measured by IFNγ‐producing cells or protection against virus infection. However, they skewed CD8 responses to a Tc17 phenotype. Thus, the apparent lack of help was actually immune deviation. This skewing depended on both IL‐21 and IL‐23. To overcome this effect, we inhibited Th17 induction by blocking TGF‐β. Anti‐TGF‐β allowed the IL‐1β adjuvant to enhance CD8+ T‐cell responses without skewing the phenotype to Tc17, thereby providing an approach to harness the benefit of common IL‐1‐inducing adjuvants like alum without immune deviation.
Reduced parahippocampal volume and psychosis symptoms in Alzheimer's disease
Authors: McLachlan Emma , Bousfield Jennifer , Howard Robert , Reeves Suzanne
Published: July 2017

Objective

Establishing structural imaging correlates of psychosis symptoms in Alzheimer's disease (AD) could localise pathology and target symptomatic treatment. This study investigated whether psychosis symptoms are associated with visuoperceptual or frontal networks, and whether regional brain volume differences could be linked with the paranoid (persecutory delusions) or misidentification (misidentification phenomena and/or hallucinations) subtypes.

Methods

A total of 104 patients with probable AD (AddNeuroMed; 47 psychotic, 57 non‐psychotic), followed up for at least one year with structural MRI at baseline. Presence and subtype of psychosis symptoms were established using the Neuropsychiatric Inventory. Volume and cortical thickness measures in visuoperceptual and frontal networks were explored using multivariate analyses to compare with both a global (psychotic versus not) and subtype‐specific approach, adjusting for potential confounding factors.

Results

There was a significant main effect of psychosis subtypes on the ventral visual stream region of interest (F30,264 = 1.65, p = 0.021, np2 = 0.16). This was explained by reduced left parahippocampal gyrus volume (F1,97 = 11.1, p = 0.001, np2 = 0.10). When comparisons were made across psychosis subtypes, left parahippocampal volume reduction remained significant (F7,95 = 3.94, p = 0.011, np2 = 0.11) and was greatest for the misidentification and mixed subtypes compared to paranoid and non‐psychotic groups.

Conclusions

These findings implicate the ventral visual stream in psychosis in AD, consistent with integrative theories regarding origins of psychosis, and provide further evidence for a role in the misidentification subtype. Specifically, reduced volume in the parahippocampal gyrus is implicated in misidentification delusion formation, which we hypothesise is due to its role in context attribution. Copyright © 2017 John Wiley & Sons, Ltd.
Protein secondary structure analysis of dried blood serum using infrared spectroscopy to identify markers for colitis screening
Authors: Titus Jitto , Ghimire Hemendra , Viennois Emilie , Merlin Didier , Unil Perera A. G.
Published: July 2017

There remains a great need for diagnosis of inflammatory bowel disease, for which the current technique, colonoscopy, is costly and also has risks for complications. Attenuated total reflectance Fourier transform infrared spectroscopy is a new screening technique to evaluate colitis. Using second derivative spectral deconvolution of the absorbance spectra, a full set of spectral markers were identified based on statistical analysis. Using this method, Amide I group frequencies, (specifically, α‐helix to β‐sheet ratio of the protein secondary structure) were identified in addition to the previously reported glucose and mannose signatures in sera of chronic and acute mice models of colitis. We also used the same technique to demonstrate that these spectral markers (α‐helix/β‐sheet ratio, glucose and mannose) are recovering to basal levels upon anti‐TNFα therapy. Hence, this technique will be able to identify changes in the sera due to diseases.
When epigenetics meets bioengineering—A material characteristics and surface topography perspective
Authors: Larsson Lena , Pilipchuk Sophia P. , Giannobile William V. , Castilho Rogerio M.
Published: July 2017

The field of tissue engineering and regenerative medicine (TE/RM) involves regeneration of tissues and organs using implantable biomaterials. The term epigenetics refers to changes in gene expression that are not encoded in the DNA sequence, leading to remodeling of the chromatin and activation or inactivation of gene expression. Recently, studies have demonstrated that these modifications are influenced not only by biological cues but also by mechanical and topographical signals. This review highlights the current knowledge on emerging approaches in TE/RM with a focus on the effect of materials and topography on the epigenetic expression pattern in cells with potential impacts on modulating regenerative biology. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2065–2071, 2018.
Surface cross‐linked ultra high molecular weight polyethylene by emulsified diffusion of dicumyl peroxide
Authors: Kayandan Sanem , Doshi Brinda N. , Oral Ebru , Muratoglu Orhun K.
Published: July 2017

Cross‐linking improves the wear resistance of ultrahigh molecular weight polyethylene (UHMWPE) used in hip and knee implants. Free radicals, generated by ionizing radiation or chemically, react to form cross‐links. Limiting cross‐linking to the articulating surface of the implant is desirable to enable high wear resistance on the surface and higher strength and toughness in the bulk. We investigated the diffusion of emulsified dicumyl peroxide (DCP) into vitamin E‐blended UHMWPE (0.1 and 0.3 wt. % vitamin‐E) with subsequent thermal decomposition in situ to obtain surface cross‐linking with the objective of achieving surface wear rate equivalent or lower than that of current clinically available materials. We diffused emulsified DCP at 100°C followed by in situ decomposition at 150°C. We also assessed the effect of having vitamin‐E in the DCP emulsion. The oxidative stability of the treated samples increased with increasing vitamin E concentration in the blend and by incorporating vitamin E into the peroxide emulsion. The impact strength of a surface cross‐linked, 0.3 wt% vitamin E blended UHMWPE prepared using this method was superior to a clinically available irradiated and melted highly cross‐linked UHMWPE while the wear resistance was comparable. These results showed the feasibility of surface cross‐linking using emulsified peroxide diffusion as a method of making tough and wear resistant joint implant bearing surfaces. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1517–1523, 2018.
Melatonin prevents mitochondrial dysfunctions and death in differentiated skeletal muscle cells
Authors: Salucci Sara , Battistelli Michela , Baldassarri Valentina , Burini Debora , Falcieri Elisabetta , Burattini Sabrina
Published: July 2017

Oxidative stress increase induces cellular damage and apoptosis activation, a mechanism believed to represent a final common pathway correlated to sarcopenia and many skeletal muscle disorders. The goal of this study is to evaluate if melatonin, a ROS scavenger molecule, is able to counteract or modulate myotube death. Here, differentiated C2C12 skeletal muscle cells have been treated with melatonin before chemicals known to induce apoptotic death and oxidative stress, and its effect has been investigated by means of morpho‐functional analyses. Ultrastructural observations show melatonin protection against triggers by the reducing of membrane blebbing, chromatin condensation, myonuclei loss and in situ DNA cleavage. Moreover, melatonin is able to prevent mitochondrial dysfunctions which occur in myotubes exposed to the trigger alone. These findings demonstrate melatonin ability in preventing apoptotic cell death in skeletal muscle fibers in vitro, suggesting for this molecule a potential therapeutic role in the treatment of various muscle disorders.
Lung Cancer: Short‐Term Reproducibility of Intravoxel Incoherent Motion Parameters and Apparent Diffusion Coefficient at 3T
Authors: Jiang Jianqin , Yin Jianbin , Cui Lei , Gu Xiaowen , Cai Rongfang , Gong Shenchu , Xu Yiming , Ma Hang , Mao Jian
Published: July 2017

Purpose

To prospectively evaluate the short‐term reproducibility of intravoxel incoherent motion (IVIM) parameters and apparent diffusion coefficient (ADC) in lung cancer patients.

Materials and Methods

In all, 50 patients (50 lesions) underwent free‐breathing diffusion‐weighted imaging (DWI) (b = 0, 300, 800 s/mm2) and IVIM (10 b‐values, 0–1000 s/mm2) scans twice (0.5–1‐hour interval) at 3T. Regions of interests (ROIs) were drawn on ADC maps and IVIM images to derive the mean ADC value and IVIM parameters D, D*, and f. Intra‐ and interobserver, test–retest reproducibility were assessed with intraclass correlation coefficients (ICCs), within coefficient‐of‐variations (WCVs), and Bland–Altman analysis. The effects of type, size, and location of lung lesions were compared with WCVs.

Results

D and ADC showed good intraobserver reproducibility and interobserver agreement, while D* and f showed relatively larger variability (WCV 20.89–34.97%). The test–retest reproducibility of D and ADC were good (ICC 0.763–0.837; WCV 11.12–12.55%), while those of D* and f were relatively poor (ICC 0.604–0.842; WCV 36.54–72.62%). D and ADC had decreased reproducibility for lesions <2 cm (WCV 14.20%, 16.34%, respectively) and for lesions in the lower lung zones (WCV 16.52%, 14.78%, respectively). f had decreased reproducibility in central lung cancers (WCV 50.11%) and lesions >2 cm (WCV 42.64%). D* had even worse reproducibility in peripheral lung cancers (WCV 84.11%) and lesions in the lower lung zones (WCV 80.84%).

Conclusion

If the change in ADC, D, D*, and f values is less than ∼31%, 34%, 170%, and 130%, respectively, it may be caused by measurement error. The type, size, and location of lung lesions have an effect on measurement errors.

Level of Evidence: 1

Technical Efficacy Stage: 1

J. Magn. Reson. Imaging 2018;47:1003–1012.
Different resuscitation strategies and novel pharmacologic treatment with valproic acid in traumatic brain injury
Authors: Dekker Simone E. , Nikolian Vahagn C. , Sillesen Martin , Bambakidis Ted , Schober Patrick , Alam Hasan B.
Published: July 2017

Traumatic brain injury (TBI) is a leading cause of death in young adults, and effective treatment strategies have the potential to save many lives. TBI results in coagulopathy, endothelial dysfunction, inflammation, cell death, and impaired epigenetic homeostasis, ultimately leading to morbidity and/or mortality. Commonly used resuscitation fluids such as crystalloids or colloids have several disadvantages and might even be harmful when administered in large quantities. There is a need for next‐generation treatment strategies (especially in the prehospital setting) that minimize cellular damage, improve survival, and enhance neurological recovery. Pharmacologic treatment with histone deacetylase inhibitors, such as valproic acid, has shown promising results in animal studies of TBI and may therefore be an excellent example of next‐generation therapy. This review briefly describes traditional resuscitation strategies for TBI combined with hemorrhagic shock and describes preclinical studies on valproic acid as a new pharmacologic agent in the treatment of TBI. It finally discusses limitations and future directions on the use of histone deacetylase inhibitors for the treatment of TBI.
Immediate and short‐term effects of real‐time knee adduction moment feedback on the peak and cumulative knee load during walking
Authors: Jackson Brennan , Gordon Keith E. , Chang Alison H.
Published: July 2017

The peak external knee adduction moment (pKAM), KAM impulse, and peak knee flexion moment (pKFM) during gait are important loading variables in medial tibiofemoral osteoarthritis. We evaluated the effects of gait modification, using real‐time pKAM visual feedback, on pKAM, KAM impulse, and pKFM; and whether participants could maintain the KAM‐reducing gait after feedback removal. Eleven healthy individuals performed a series of walking trials on a split‐belt instrumented treadmill under four conditions of Baseline, Feedback, No Feedback Early, and No Feedback Late. Guided by real‐time feedback of pKAM, they modified their gait patterns to lower pKAM by 20%. Three‐dimensional joint kinematics/kinetics during each walking condition were recorded by a 12‐camera motion capture system and the instrumented treadmill. Change in each knee loading parameter from baseline across conditions was assessed using one‐way repeated‐measures analysis‐of‐variances. In the feedback limb, successful 20% reductions from baseline in pKAM and KAM impulse were achieved across all three conditions. There was a trend for concomitant pKFM increases, partially attenuating the beneficial effects of pKAM reduction. A carry‐over effect of KAM reduction in the non‐feedback limb was noted. The altered gait patterns were participant‐specific and multi‐modal; each participant reported a combination of two to three gait modification strategies used for pKAM reduction. Toe‐in and medial foot contact were the most reported strategies. The findings support the real‐time pKAM visual feedback as a tool for individualized gait modification to reduce knee load. Future studies to evaluate its effectiveness in persons with or at risk for medial knee osteoarthritis is warranted. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:397–404, 2018.
Bayesian one‐step IPD network meta‐analysis of time‐to‐event data using Royston‐Parmar models
Authors: Freeman Suzanne C. , Carpenter James R.
Published: July 2017

Network meta‐analysis (NMA) combines direct and indirect evidence from trials to calculate and rank treatment estimates. While modelling approaches for continuous and binary outcomes are relatively well developed, less work has been done with time‐to‐event outcomes. Such outcomes are usually analysed using Cox proportional hazard (PH) models. However, in oncology with longer follow‐up time, and time‐dependent effects of targeted treatments, this may no longer be appropriate. Network meta‐analysis conducted in the Bayesian setting has been increasing in popularity. However, fitting the Cox model is computationally intensive, making it unsuitable for many datasets. Royston‐Parmar models are a flexible alternative that can accommodate time‐dependent effects. Motivated by individual participant data (IPD) from 37 cervical cancer trials (5922 women) comparing surgery, radiotherapy, and chemotherapy, this paper develops an IPD Royston‐Parmar Bayesian NMA model for overall survival. We give WinBUGS code for the model. We show how including a treatment‐ln(time) interaction can be used to conduct a global test for PH, illustrate how to test for consistency of direct and indirect evidence, and assess within‐design heterogeneity. Our approach provides a computationally practical, flexible Bayesian approach to NMA of IPD survival data, which readily extends to include additional complexities, such as non‐PH, increasingly found in oncology trials.
A quantified risk‐scoring system and rating model for postsurgical gastroparesis syndrome in gastric cancer patients
Authors: Chen Xiao‐dong , Mao Chen‐chen , Zhang Wei‐teng , Lin Ji , Wu Rui‐sen , Zhang Feng‐min , Sun Xiang‐wei , Chi Chu‐huai , Shen Xian , Wang Peng‐fei
Published: July 2017

Background and Objectives

The study aimed to investigate the relationship between obesity and postsurgical gastroparesis syndrome (PGS), and to construct a scoring system and a risk model to identify patients at high risk.

Methods

A total of 634 patients were retrospectively analyzed. Clinical characteristics were evaluated via receiver operating characteristic (ROC) curve analysis. Logistic analysis was performed to determine the independent predictive indicators of PGS. A scoring system consisting of these indicators and a risk‐rating model were constructed and evaluated via ROC curve analysis.

Results

Based on the ROC curves, the visceral fat area (VFA) cutoff value for PGS was 94.00. Logistic analysis showed that visceral obesity (VFA ≥ 94.00 cm2), the reconstruction technique, and tumor size were independent prognostic factors for PGS. The scoring system could predict PGS reliably with a high area under the ROC curve ([AUC] = 0.769). A high‐risk rating had a high AUC (AUC I = 0.56, AUC II = 0.65, and AUC III = 0.77), indicating that the risk‐rating model could effectively screen patients at high risk of PGS.

Conclusions

Visceral obesity defined by VFA effectively predicted PGS. Our scoring system may be a reliable instrument for identifying patients most at risk of PGS.
Prevalence of psychiatric comorbidities among women undergoing free tissue autologous breast reconstruction
Authors: Becherer Babette E. , Kamali Parisa , Paul Marek A. , Wu Winona , Curiel Daniel A. , Rakhorst Hinne A. , Lee Bernard , Lin Samuel J. , Kansal Kari J.
Published: July 2017

Background and Objectives

Autologous breast reconstruction (BR) can be a stressful life event. Therefore, women undergoing mastectomy and autologous BR are required to have sufficient coping mechanisms. Although mental health problems are widespread, information regarding the prevalence of psychiatric diagnosis among these patients is scarce.

Methods

Retrospective analysis was performed using data from a large tertiary teaching hospital and the Nationwide Inpatient Sample (NIS) database. Patients undergoing autologous BR after mastectomy were included and evaluated for psychiatric disorders. Prevalence of each disorder, timing of diagnosis (preoperative or postoperative), and data per age group were reviewed.

Results

Between 2004 and 2014, 817 patients were included from the institutional database and 26 399 from the NIS database. Preoperatively, 15.3% of the patients were diagnosed with a psychiatric disorder within our institution and 17.6% nationwide (P < 0.001). Postoperatively, 20.5% of the institutional patients were diagnosed with a psychiatric disorder. No major differences in prevalence were seen between age groups.

Conclusions

Approximately, one in six patients were diagnosed with a psychiatric comorbidity preoperatively. Postoperatively, an additional 20.5% developed a psychiatric disorder. There was no difference in prevalence and timing of diagnosis between age groups.
Increased Mindfulness Skills as Predictors of Reduced Trauma‐Related Guilt in Treatment‐Seeking Veterans
Authors: Held Philip , Owens Gina P. , Monroe J. Richard , Chard Kathleen M.
Published: July 2017

The present study examined the predictive role of increased self‐reported mindfulness skills on reduced trauma‐related guilt in a sample of veterans over the course of residential treatment for posttraumatic stress disorder (PTSD; N = 128). The residential treatment consisted of seven weeks of intensive cognitive processing therapy (CPT) for PTSD, as well as additional psychoeducational groups, including seven sessions on mindfulness skills. Increased mindfulness skills describing, acting with awareness, and accepting without judgment were significantly associated with reductions in trauma‐related guilt over the course of treatment. Increases in the ability to act with awareness and accept without judgment were significantly associated with reductions in global guilt, R2 = .26, guilt distress, R2= .23, guilt cognitions, R2= .23, and lack of justification, R2= .11. An increase in the ability to accept without judgment was the only self‐reported mindfulness skill that was associated with reductions in hindsight bias, β = −.34 and wrongdoing, β = −.44. Increases in self‐reported mindfulness skills explained 15.1 to 24.1% of the variance in reductions in trauma‐related guilt, suggesting that mindfulness skills may play a key role in reducing the experience of trauma‐related guilt during psychotherapy. Our results provide preliminary support for the use of mindfulness groups as an adjunct to traditional evidence‐based treatments aimed at reducing trauma‐related guilt, though this claim needs to be tested further using experimental designs.
Tailoring the Morphology of Responsive Bioinspired Bicomponent Fibers
Authors: Gernhardt Marvin , Peng Ling , Burgard Matthias , Jiang Shaohua , Förster Beate , Schmalz Holger , Agarwal Seema
Published: July 2017

Nature is an intriguing inspiration for designing a myriad of functional materials. However, artificial mimicking of bioinspired structures usually requires different specialized procedures and setups. In this study, a new upscalable concept is presented that allows to produce two bioinspired, bicomponent fiber morphologies (side‐by‐side and coaxial bead‐on‐string) using the same electrospinning setup, just by changing the employed spinning solvent. The generated fiber morphologies are highly attractive for thermoresponsive actuation and water harvesting. Another challenge solved in this work is the compositional characterization of complex fiber morphologies. Raman imaging and atomic force microscopy is introduced as a powerful method for the unambiguous characterization of complex bicomponent fiber morphologies. The work opens the way for the construction of heterostructured fiber morphologies based on different polymers combinations, offering high potential for applications as actuators, smart textiles, water management, drug release, and catalysis.