bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative outcomes of transcatheter aortic valve replacement in African American and Caucasian patients with severe aortic stenosis
Authors: Alqahtani Fahad , Aljohani Sami , Almustafa Ahmad , Alhijji Mohammed , Ali Oluseun , Holmes David R. , Alkhouli Mohamad
Published: September 2017

Background

Racial disparities in cardiovascular care have been extensively investigated. The introduction of transcatheter aortic valve replacement (TAVR) revolutionized the treatment of aortic stenosis (AS) in the last decade. Whether a racial disparity in the utilization and outcome of TAVR exists is unknown.

Methods

We utilized the nationwide inpatient sample (NIS) to compare utilization rates, and in‐hospital outcomes of Caucasians and African American (AA) patients who underwent TAVR between August 2011 and December 2014.

Results

A total of 7,176 patients (6870 Caucasians, 95.7%) and (306 AAs, 4.3%) were included in this analysis. Among patients who underwent aortic valve replacement between 2011 and 2014, the rates of TAVR utilization increased from 0.32% to 7.6% in AAs and from 0.4% to 8.8% in Caucasians. In propensity‐matched cohorts of patients (n = 300 Caucasians and n = 300 AAs), in‐hospital mortality was similar (3.7% and 3.3%, respectively, P = 0.99). Also, rates of key complications including stroke, permanent pacemaker implantation (PPMI), vascular complications, acute kidney injury, new dialysis, blood transfusion, and tamponade were similar in both races. There was also no significant difference between Caucasians and AAs with regards to length of stay, cost of hospitalization, and intermediate care facility utilization.

Conclusions

There was no significant difference in the utilization rates, in‐hospital outcomes, and cost of TAVR between Caucasians and AA patients in contemporary US practice. Further comparative studies of surgical and TAVR in AAs and other racial minorities are warranted.
Large‐scale oxidation of multi‐walled carbon nanotubes in fluidized bed from ozone‐containing gas mixtures
Authors: Lassègue Pierre , Noé Laure , Dupin Jean‐Charles , Monthioux Marc , Caussat Brigitte
Published: September 2017

100 g of multi‐walled carbon nanotubes (MWCNTs) tangled in balls of 388 μm in Sauter diameter were treated per run in a pre‐industrial scale fluidized bed reactor, using ozone‐based gaseous mixtures at ambient temperature. The influence of ozone concentration and of the addition of water vapour was studied, for treatment durations between 1 h and 20 h. The process behaviour was analyzed in terms of fluidized bed pressure drop and temperature profile. The nature and amount of the grafted oxygen based functions were analyzed, as the structural modifications created. An oxidation mechanism in two steps was evidenced, showing the grafting of hydroxyl, phenol, and ether functions in a first step and then of lactone, quinone, carbonyl, and carboxylic groups. A moderate etching of the MWCNT outer walls was observed. The amount of grafted functions and of structural defects increased with treatment duration and was highly exalted by the presence of water vapour. All the results obtained showed that the oxidation was uniform on the whole powder of the bed and from the outer part to the centre of the balls, probably thanks to the high fluidization quality maintained all along the ozone treatment.
Comprehensive Pharmacogenomic Study Reveals an Important Role of UGT1A3 in Montelukast Pharmacokinetics
Authors: Hirvensalo Päivi , Tornio Aleksi , Neuvonen Mikko , Tapaninen Tuija , Paile‐Hyvärinen Maria , Kärjä Vesa , Männistö Ville T. , Pihlajamäki Jussi , Backman Janne T. , Niemi Mikko
Published: September 2017

To identify the genetic basis of interindividual variability in montelukast exposure, we determined its pharmacokinetics and sequenced 379 pharmacokinetic genes in 191 healthy volunteers. An intronic single nucleotide variation (SNV), strongly linked with UGT1A3*2, associated with reduced area under the plasma concentration–time curve (AUC0‐∞) of montelukast (by 18% per copy of the minor allele; P = 1.83 × 10−10). UGT1A3*2 was associated with increased AUC0‐∞ of montelukast acyl‐glucuronide M1 and decreased AUC0‐∞ of hydroxymetabolites M5R, M5S, and M6 (P < 10−9). Furthermore, SNVs in SLCO1B1 and ABCC9 were associated with the AUC0‐∞ of M1 and M5R, respectively. In addition, a candidate gene analysis suggested that CYP2C8 and ABCC9 SNVs also affect the AUC0‐∞ of montelukast. The found UGT1A3 and ABCC9 variants associated with increased expression of the respective genes in human liver samples. Montelukast and its hydroxymetabolites were glucuronidated by UGT1A3 in vitro. These results indicate that UGT1A3 plays an important role in montelukast pharmacokinetics, especially in UGT1A3*2 carriers.
Non‐Aqueous Primary Li–Air Flow Battery and Optimization of its Cathode through Experiment and Modeling
Authors: Kim Byoungsu , Takechi Kensuke , Ma Sichao , Verma Sumit , Fu Shiqi , Desai Amit , Pawate Ashtamurthy S. , Mizuno Fuminori , Kenis Paul J. A.
Published: September 2017

A primary Li–air battery has been developed with a flowing Li‐ion free ionic liquid as the recyclable electrolyte, boosting power capability by promoting superoxide diffusion and enhancing discharge capacity through separately stored discharge products. Experimental and computational tools are used to analyze the cathode properties, leading to a set of parameters that improve the discharge current density of the non‐aqueous Li–air flow battery. The structure and configuration of the cathode gas diffusion layers (GDLs) are systematically modified by using different levels of hot pressing and the presence or absence of a microporous layer (MPL). These experiments reveal that the use of thinner but denser MPLs is key for performance optimization; indeed, this leads to an improvement in discharge current density. Also, computational results indicate that the extent of electrolyte immersion and porosity of the cathode can be optimized to achieve higher current density.
Cytopathological and immunocytochemical findings of pancreatic anaplastic carcinoma with ZEB1 expression by means of touch imprint cytology
Authors: Naito Yoshiki , Kawahara Akihiko , Taira Tomoki , Takase Yorihiko , Murata Kazuya , Ishida Yusuke , Okabe Yoshinobu , Tanigawa Masahiko , Mihara Yutaro , Nakayama Masamichi , Shimamatsu Kazuhide , Yano Hirohisa , Akiba Jun
Published: September 2017

Pancreatic anaplastic carcinoma (PAC) is rare and has an aggressive clinical course. We report an autopsy case of PAC focusing on the cytopathological characteristics of the tumor and immunocytochemical staining for vimentin, E‐cadherin, and zinc finger E‐box binding homeobox 1 (ZEB1), which markers are associated with epithelial markers of epithelial‐mesenchymal transition (EMT). A 50‐year‐old woman presented to our hospital with a chief complaint of jaundice. A pancreatic head tumor and multiple liver nodules were detected on abdominal computed tomography. Biliary cytology under endoscopic retrograde cholangiopancreatography suggested ductal adenocarcinoma. Three months after admission, she died of multiorgan failure. At autopsy, touch imprint cytology using squash preparation of the pancreatic tumor identified two different cell types; numerous isolated malignant cells with large and pleomorphic nuclei and a few clusters showing irregularly overlapped nuclei and irregular contours within the necrotic background. Immunocytochemically, isolated cells were positive for vimentin and ZEB1, and negative for E‐cadherin. Conversely, clusters were negative for vimentin and ZEB1, and positive for E‐cadherin. Histologically, the tumor was composed of sarcomatous cells with small foci of adenocarcinoma, which were consistent with a diagnosis of PAC. Immunohistochemical staining of the adenocarcinoma and sarcomatous cells corresponded to those of the clusters and isolated malignant cells, respectively. Immunostaining of these EMT markers is useful to distinguish sarcomatous cells from adenocarcinoma and can contribute to the accurate diagnosis of pancreatic tumors with EMT.
Pitfalls in the cytological diagnosis of tenosynovial giant cell tumor: An illustration of eight discordant cases
Authors: Mondal Krishnendu , Mandal Rupali , Khan Kalyan , Chakraborty Jasashwi
Published: September 2017

Tenosynovial giant cell tumor (TSGCT) is a highly recurrent benign tumor of the extremities. Wide local excision is usually sufficient to achieve its recurrence‐free outcome. However, that needs a confident pre‐operative cytological diagnosis as TSGCT. Aspirates from this tumor express the characteristic polymorphic cytological pattern, enough to impose a definite diagnosis. However rarely so, inadequate sampling from smaller tumors or due to faulty techniques, and selective sampling from topographic clusters of any individual component may lead to wrong interpretation. An unorthodox location near the larger limb joints further complicates the diagnostic misery on occasions. Such tumors are amenable to incomplete removal and risk for future recurrence. In this report, we describe eight cases of TSGCTs that were cytologically diagnosed otherwise. The cytological features of these discrepant tumors and the factors attributable to such dilemma are elaborated. Finally, a possible remedy has been proposed at conclusion in order to avoid future inconveniences.
Asymmetric development of the nervous system
Authors: Alqadah Amel , Hsieh Yi‐Wen , Morrissey Zachery D. , Chuang Chiou‐Fen
Published: September 2017

The human nervous system consists of seemingly symmetric left and right halves. However, closer observation of the brain reveals anatomical and functional lateralization. Defects in brain asymmetry correlate with several neurological disorders, yet our understanding of the mechanisms used to establish lateralization in the human central nervous system is extremely limited. Here, we review left‐right asymmetries within the nervous system of humans and several model organisms, including rodents, Zebrafish, chickens, Xenopus, Drosophila, and the nematode Caenorhabditis elegans. Comparing and contrasting mechanisms used to develop left‐right asymmetry in the nervous system can provide insight into how the human brain is lateralized. Developmental Dynamics 247:124–137, 2018. © 2017 Wiley Periodicals, Inc.
Land use impacts on floodplain water table response to precipitation events
Authors: Kellner Elliott , Hubbart Jason A.
Published: September 2017

Two floodplain sites were instrumented, a bottomland hardwood forest and a historic agricultural field. Continuous, automated, in situ shallow groundwater monitoring was paired with a gridded sampling design to facilitate detailed spatiotemporal analysis of water table response to precipitation events. Data were collected at 30‐min intervals for the duration of the 2011, 2012, 2013, and 2014 water years. Four hundred three precipitation events were observed, with median depth of 3 mm. Results show significantly (p < .001) greater study site median water table response at the agricultural site (0.02 m), relative to the forest (0.01 m). The ratio of water table response magnitude to precipitation depth was 8.3 and 3.3 at the agricultural and forest sites, respectively, a difference of more than 150%. Median shallow groundwater level lag time was shorter with respect to both precipitation and streamflow at the agricultural site (10 and 2 hr for precipitation and flow, respectively), relative to the forest (11.5 and 4.5 hr for precipitation and flow, respectively). Longer lag times indicated slower water table response and potentially increased flood attenuation capacity by the forest site. Results show the agricultural site water table responded to a greater number of precipitation events (including smaller events), reflecting potentially reduced relative flood attenuation capacity. Observed differences highlight the various impacts of forest vegetation on water table dynamics and emphasize the benefits of floodplain forests as a water resource management tool, including for flood mitigation, in mixed‐land‐use watersheds.
Trichostatin A preferentially reverses the upregulation of gene‐expression levels induced by gain of chromosome 7 in colorectal cancer cell lines
Authors: Buishand Floryne O. , Cardin Eric , Hu Yue , Ried Thomas
Published: September 2017

Epithelial cancers are defined by a tumor‐specific distribution of chromosomal aneuploidies that are maintained when cells metastasize and are conserved in cell lines derived from primary tumors. Correlations between genomic copy number and gene expression have been observed for different tumors including, colorectal (CRC), breast, and pancreatic cancer. These ploidy‐driven transcriptional deregulations are characterized by low‐level expression changes of most genes on the affected chromosomes. The emergence of these aberrations at an early stage of tumorigenesis and the strong selection for the maintenance of these aneuploidies suggest that aneuploidy‐dependent transcriptional deregulations might contribute to cellular transformation and maintenance of the malignant phenotype. The histone deacetylase inhibitor (HDACi) Trichostatin A (TSA) has anticancer effects and is well known to lead to large‐scale gene‐expression changes. Here we assessed if TSA could disrupt the aneuploidy‐driven gene expression in the aneuploid colon cancer cell line SW480 and the artificially generated aneuploid cell line DLD‐1 + 7. We found that TSA increases transcriptional activity throughout the genome, yet inhibits aneuploidy‐induced gene‐expression changes on chromosome 7. Among the TSA affected genes on chromosome 7, we identified potential CRC oncogenes. These experiments represent the first attempt to explain how histone acetylation affects aneuploidy‐driven gene‐expression changes.
Hepatitis C virus testing for case identification in persons born during 1945‐1965: Results from three randomized controlled trials
Authors: Yartel Anthony K. , Rein David B. , Brown Kimberly Ann , Krauskopf Katherine , Massoud Omar I. , Jordan Cynthia , Kil Natalie , Federman Alex D. , Nerenz David R. , Brady Joanne E. , Kruger Danielle L. , Smith Bryce D.
Published: September 2017

The Centers for Disease Control and Prevention and US Preventive Services Task Force recommend one‐time hepatitis C virus (HCV) testing for persons born during 1945‐1965 (birth cohort). However, few studies estimate the effect of birth cohort (BC) testing implementation on HCV diagnoses in primary care settings. We aimed to determine the probability of identifying HCV infections in primary care using targeted BC testing compared with usual care at three academic medical centers. From December 2012 to March 2014, each center compared one of three distinct interventions with usual care using an independently designed randomized controlled trial. Across centers, BC patients with no clinical documentation of previous HCV testing or diagnosis were randomly assigned to receive a one‐time offering of HCV antibody (anti‐HCV) testing via one of three independent implementation strategies (repeated‐mailing outreach, electronic medical record–integrated provider best practice alert [BPA], and direct patient solicitation) or assigned to receive usual care. We estimated model‐adjusted risk ratios (aRR) of anti–HCV‐positive (anti‐HCV+) identification using BC testing versus usual care. In the repeated mailing trial, 8992 patients (intervention, n = 2993; control, n = 5999) were included in the analysis. The intervention was eight times as likely to identify anti‐HCV+ patients compared with controls (aRR, 8.0; 95% confidence interval [CI], 2.8‐23.0; adjusted probabilities: intervention, 0.27%; control, 0.03%). In the BPA trial, data from 14,475 patients (BC, n = 8928; control, n = 5,547) were analyzed. The intervention was 2.6 times as likely to identify anti‐HCV+ patients versus controls (aRR, 2.6; 95% CI, 1.1‐6.4; adjusted probabilities: intervention, 0.29%; control, 0.11%). In the patient‐solicitation trial, 8873 patients (BC, n = 4307; control, n = 4566) were analyzed. The intervention was five times as likely to identify anti‐HCV+ patients compared with controls (aRR, 5.3; 95% CI, 2.3‐12.3; adjusted probabilities: intervention, 0.68%; control, 0.11%). Conclusion: BC testing was effective in identifying previously undiagnosed HCV infections in primary care settings. (Hepatology 2018;67:524‐533).
Flexible wide‐field optical micro‐angiography based on Fourier‐domain multiplexed dual‐beam swept source optical coherence tomography
Authors: Song Shaozhen , Xu Jingjiang , Wang Ruikang K.
Published: September 2017

Wide‐field optical coherence tomography angiography (OCTA) is gaining interest in clinical imaging applications. In this pursuit, it is challenging to maintain the imaging resolution and sensitivity throughout the wide field of view (FoV). Here, we propose a novel method/system of dual‐beam arrangement and Fourier‐domain multiplexing to achieve wide‐field OCTA when imaging the uneven surface samples. The proposed system provides 2 separate FoVs, with flexibility that the imaging area, focus of the imaging beam and imaging depth range can be individually adjusted for each FoV, leading to either (1) increased system imaging FoV or (2) capability of targeting 2 regions of interests that locate at depths with large difference between each other. We demonstrate this novel method by employing 100 kHz laser source in a swept source OCTA to achieve an effective 200 kHz sweeping rate, covering a 22 × 22 mm FoV. The results are verified by a SS‐OCTA system employing a 200 kHz laser source, together with the experimental demonstrations when imaging whole brain vasculature in rodent models and skin blood perfusion in human fingers, show‐casing the capability of proposed system to image live large samples with complex surface topography.
An in vitro simulation model to assess the severity of edge loading and wear, due to variations in component positioning in hip joint replacements
Authors: O'Dwyer Lancaster‐Jones O. , Williams S. , Jennings L. M. , Thompson J. , Isaac G. H. , Fisher J. , Al‐Hajjar M.
Published: September 2017

The aim of this study was to develop a preclinical in vitro method to predict the occurrence and severity of edge loading condition associated with the dynamic separation of the centres of the head and cup (in the absence of impingement) for variations in surgical positioning of the cup. Specifically, this study investigated the effect of both the variations in the medial–lateral translational mismatch between the centres of the femoral head and acetabular cup and the variations in the cup inclination angles on the occurrence and magnitude of the dynamic separation, the severity of edge loading, and the wear rate of ceramic‐on‐ceramic hip replacement bearings in a multi‐station hip joint simulator during a walking gait cycle. An increased mismatch between the centres of rotation of the femoral head and acetabular cup resulted in an increased level of dynamic separation and an increase in the severity of edge loading condition which led to increased wear rate in ceramic‐on‐ceramic bearings. Additionally for a given translational mismatch, an increase in the cup inclination angle gave rise to increased dynamic separation, worst edge loading conditions, and increased wear. To reduce the occurrence and severity of edge loading, the relative positions (the mismatch) of the centres of rotation of the head and the cup should be considered alongside the rotational position of the acetabular cup. This study has considered the combination of mechanical and tribological factors for the first time in the medial–lateral axis only, involving one rotational angle (inclination) and one translational mismatch. © 2017 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1897–1906, 2018.
The influence of two common sterilization techniques on the corrosion of Mg and its alloys for biomedical applications
Authors: Johnston Sean , Shi Zhiming , Hoe Cherilyn , Uggowitzer Peter J. , Cihova Martina , Löffler Jörg F. , Dargusch Matthew S. , Atrens Andrej
Published: September 2017

This paper studied the influence of two common sterilization techniques, ethylene oxide (EO) and gamma irradiation (GI), on the corrosion rate of four Mg‐based materials in CO2‐bicarbonate buffered Hanks’ solution. The four materials were: high‐purity (HP)‐Mg, ZE41, ultra‐high purity (XHP)‐Mg, and XHP‐ZX00. The corrosion rate was measured through mass loss (Pm) and hydrogen evolution (PH). Two‐way analysis of variance (ANOVA) was conducted to assess the effect of the sterilization techniques on the corrosion rates across the four materials. The ANOVA analyzed the variables of (1) material, (2) sterilization condition (EO, GI, and an unsterilized control group), and (3) the interaction between these two independent variables. Neither sterilization technique (EO and GI) significantly influenced the corrosion rate as measured byPm(p < 0.84) norPH(p < 0.08). This result was consistent across the four materials tested, as there was no interaction between the test variables of material and sterilization condition forPm(p < 0.49) orPH(p < 0.27). As neither EO nor GI influenced the corrosion rates, either of these techniques warrants consideration for use on Mg‐based medical implants and devices. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1907–1917, 2018.
Bicarbonate Recycling by HIF-1–Dependent Carbonic Anhydrase Isoforms 9 and 12 Is Critical in Maintaining Intracellular pH and Viability of Nucleus Pulposus Cells
Authors: Silagi Elizabeth S , Schoepflin Zachary R , Seifert Erin L , Merceron Christophe , Schipani Ernestina , Shapiro Irving M , Risbud Makarand V
Published: September 2017

Intervertebral disc degeneration is a ubiquitous condition closely linked to chronic low-back pain. The health of the avascular nucleus pulposus (NP) plays a crucial role in the development of this pathology. We tested the hypothesis that a network comprising HIF-1α, carbonic anhydrase (CA) 9 and 12 isoforms, and sodium-coupled bicarbonate cotransporters (NBCs) buffer intracellular pH through coordinated bicarbonate recycling. Contrary to the current understanding of NP cell metabolism, analysis of metabolic-flux data from Seahorse XF analyzer showed that CO2 hydration contributes a significant source of extracellular proton production in NP cells, with a smaller input from glycolysis. Because enzymatic hydration of CO2 is catalyzed by plasma membrane-associated CAs we measured their expression and function in NP tissue. NP cells robustly expressed isoforms CA9/12, which were hypoxia-inducible. In addition to increased mRNA stability under hypoxia, we observed binding of HIF-1α to select hypoxia-responsive elements on CA9/12 promoters using genomic chromatin immunoprecipitation. Importantly, in vitro loss of function studies and analysis of discs from NP-specific HIF-1α null mice confirmed the dependency of CA9/12 expression on HIF-1α. As expected, inhibition of CA activity decreased extracellular acidification rate independent of changes in HIF activity or lactate/H+ efflux. Surprisingly, CA inhibition resulted in a concomitant decrease in intracellular pH that was mirrored by inhibition of sodium-bicarbonate importers. These results suggested that extracellular bicarbonate generated by CA9/12 is recycled to buffer cytosolic pH fluctuations. Importantly, long-term intracellular acidification from CA inhibition lead to compromised cell viability, suggesting that plasma-membrane proton extrusion pathways alone are not sufficient to maintain homeostatic pH in NP cells. Taken together, our studies show for the first time that bicarbonate buffering through the HIF-1α–CA axis is critical for NP cell survival in the hypoxic niche of the intervertebral disc. © 2017 American Society for Bone and Mineral Research.
Paired comparison of therapeutic plasma exchange using the Fenwal Amicus versus TerumoBCTSpectra Optia
Authors: Burgstaler Edwin A. , Bryant Sandra C. , Winters Jeffrey L.
Published: September 2017

Purpose

Terumo BCT Spectra Optia (O) and Fenwal Amicus (A) can perform therapeutic plasma exchange (TPE). We compared these systems in a prospective, randomized, crossover study of 81 paired procedures. Primary objective was to determine if there was a difference in platelet loss between the instruments. Secondary objectives were to determine differences in procedure time (PT), plasma removal efficiency (PRE 1), plasma removal rate (PRR), and fluid balance (FB).

Methods

Fifty‐seven adults undergoing 162 procedures were included. Diagnoses included neurologic, nephrologic, and hematologic diseases. Replacement fluids included 5% normal serum albumin and/or fresh frozen plasma. The first instrument (randomized) established the inlet flow rate for the second with a maximum inlet rate of 120 ml/min. Spun HCT was used to program the procedure. One plasma volume was exchanged, for both instruments. Multivariable general estimating equations were used to assess the relationship between the outcome variables with machine after adjusting for covariates, with P values <.05 significant.

Results

Median total blood volume (4,775 mL‐A, 4,775 mL‐O) and preprocedure spun HCT (33%‐A, 34%‐O) were not statistically different. The plasma removed (3196 mL‐A, 3120 mL‐O), PLT in waste plasma (0.62 × 1011‐A, 0.33 × 1011‐O), PLT decline (8.5%‐A, 6.5%‐O), and PRR (48.1 mL/min‐A, 49.2 mL/min‐O) were not statistically different. There were statistically significant, but clinically irrelevant, differences in PLT CE1 (6.2%‐A, 3.6%‐O), PRE 1 (85.3%‐A, 83.9%‐O), FB (+2 mL‐A,+15 mL‐O), and PT (71 min‐A, 71 min‐O).

Conclusions

Statistical differences were seen but none were of a magnitude to be clinically relevant, indicating comparable TPE performance.
Ergodicity and model quality in template‐restrained canonical and temperature/Hamiltonian replica exchange coarse‐grained molecular dynamics simulations of proteins
Authors: Karczyńska Agnieszka S. , Czaplewski Cezary , Krupa Paweł , Mozolewska Magdalena A. , Joo Keehyoung , Lee Jooyoung , Liwo Adam
Published: September 2017

Molecular simulations restrained to single or multiple templates are commonly used in protein‐structure modeling. However, the restraints introduce additional barriers, thus impairing the ergodicity of simulations, which can affect the quality of the resulting models. In this work, the effect of restraint types and simulation schemes on ergodicity and model quality was investigated by performing template‐restrained canonical molecular dynamics (MD), multiplexed replica‐exchange molecular dynamics, and Hamiltonian replica exchange molecular dynamics (HREMD) simulations with the coarse‐grained UNRES force field on nine selected proteins, with pseudo‐harmonic log‐Gaussian (unbounded) or Lorentzian (bounded) restraint functions. The best ergodicity was exhibited by HREMD. It has been found that non‐ergodicity does not affect model quality if good templates are used to generate restraints. However, when poor‐quality restraints not covering the entire protein are used, the improved ergodicity of HREMD can lead to significantly improved protein models. © 2017 Wiley Periodicals, Inc.
Targeted therapy of human glioblastoma via delivery of a toxin through a peptide directed to cell surface nucleolin
Authors: Dhez Anne‐Chloé , Benedetti Elisabetta , Antonosante Andrea , Panella Gloria , Ranieri Brigida , Florio Tiziana M. , Cristiano Loredana , Angelucci Francesco , Giansanti Francesco , Di Leandro Luana , d'Angelo Michele , Melone Marina , De Cola Antonella , Federici Luca , Galzio Renato , Cascone Ilaria , Raineri Fabio , Cimini Annamaria , Courty José , Giordano Antonio , Ippoliti Rodolfo
Published: September 2017

Targeted anticancer therapies demand discovery of new cellular targets to be exploited for the delivery of toxic molecules and drugs. In this perspective, in the last few years, nucleolin has been identified as an interesting surface marker to be used for the therapy of glioblastoma. In this study, we investigated whether a synthetic antagonist of cell‐surface nucleolin known as N6L, previously reported to decrease both tumor growth and tumor angiogenesis in several cancer cell lines, including glioblastoma cells, as well as endothelial cells proliferation, could be exploited to deliver a protein toxin (saporin) to glioblastoma cells. The pseudopeptide N6L cross‐linked to saporin‐S6 induced internalization of the toxin inside glioblastoma cancer cells. Our results in vitro demonstrated the effectiveness of this conjugate in inducing cell death, with an ID50 four orders of magnitude lower than that observed for free N6L. Furthermore, the preliminary in vivo study demonstrated efficiency in reducing the tumor mass in an orthotopic mouse model of glioblastoma.
Enzymatic ring‐opening polymerization (ROP) of polylactones: roles of non‐aqueous solvents
Authors: Zhao Hua
Published: September 2017

Aliphatic polyesters such as polylactides (PLAs) and other polylactones are thermoplastic, biodegradable and biocompatible polymers with the potential to replace petro‐chemical‐based synthetic polymers. A benign route for synthesizing these polyesters is through the enzyme‐catalyzed ring‐opening polymerization (ROP) reaction; this type of enzymatic process is very sensitive to reaction conditions such as solvents, water content and temperature. This review systematically evaluates the crucial roles of different solvents (such as solvent‐free/in bulk, organic solvents, supercritical fluids, ionic liquids, and aqueous biphasic systems) on the degree of polymerization and polydispersity. In general, many studies suggest that hydrophobic organic solvents with minimum water contents lead to efficient enzymatic polymerization and subsequently high molecular weights of polyesters; the selection of solvents is also limited by the reaction temperature, e.g. the ROP of lactide is often conducted at above 100 °C, therefore, the solvent typically needs to have its boiling point above this temperature. The use of supercritical fluids could be limited by its scaling‐up potential, while ionic liquids have exhibited many advantages including their low‐volatility, high thermal stability, controllable enzyme‐compatibility, and a wide range of choices. However, the fundamental and mechanistic understanding of the specific roles of ionic liquids in enzymatic ROP reactions is still lacking. Furthermore, the lipase specificity towards l‐ and d‐lactide is also surveyed, followed by the discussion of engineered lipases with improved enantioselectivity and thermal stability. In addition, the preparation of polyester‐derived materials such as polyester‐grafted cellulose by the enzymatic ROP method is briefly reviewed. © 2017 Society of Chemical Industry
Giant pseudoaneurysm of the external carotid artery causing stroke: A case report
Authors: Budinčević Hrvoje , Milošević Marina , Pavlović Tomislav
Published: September 2017

We report a patient in whom mechanical compression of the internal carotid artery by a giant external carotid artery pseudoaneurysm caused a stroke. This was a case of vascular Eagle syndrome due to the impingement of an elongated styloid process on the external carotid artery with subsequent dissection and formation of a pseudoaneurysm. Carotid ultrasonographic examination allowed distinguishing the pseudoaneurysm from other vascular and solid masses of the neck.
Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis
Authors: Miura Fumihiko , Okamoto Kohji , Takada Tadahiro , Strasberg Steven M. , Asbun Horacio J. , Pitt Henry A. , Gomi Harumi , Solomkin Joseph S. , Schlossberg David , Han Ho‐Seong , Kim Myung‐Hwan , Hwang Tsann‐Long , Chen Miin‐Fu , Huang Wayne Shih‐Wei , Kiriyama Seiki , Itoi Takao , Garden O. James , Liau Kui‐Hin , Horiguchi Akihiko , Liu Keng‐Hao , Su Cheng‐Hsi , Gouma Dirk J. , Belli Giulio , Dervenis Christos , Jagannath Palepu , Chan Angus C. W. , Lau Wan Yee , Endo Itaru , Suzuki Kenji , Yoon Yoo‐Seok , de Santibañes Eduardo , Giménez Mariano Eduardo , Jonas Eduard , Singh Harjit , Honda Goro , Asai Koji , Mori Yasuhisa , Wada Keita , Higuchi Ryota , Watanabe Manabu , Rikiyama Toshiki , Sata Naohiro , Kano Nobuyasu , Umezawa Akiko , Mukai Shuntaro , Tokumura Hiromi , Hata Jiro , Kozaka Kazuto , Iwashita Yukio , Hibi Taizo , Yokoe Masamichi , Kimura Taizo , Kitano Seigo , Inomata Masafumi , Hirata Koichi , Sumiyama Yoshinobu , Inui Kazuo , Yamamoto Masakazu
Published: September 2017

The initial management of patients with suspected acute biliary infection starts with the measurement of vital signs to assess whether or not the situation is urgent. If the case is judged to be urgent, initial medical treatment should be started immediately including respiratory/circulatory management if required, without waiting for a definitive diagnosis. The patient's medical history is then taken; an abdominal examination is performed; blood tests, urinalysis, and diagnostic imaging are carried out; and a diagnosis is made using the diagnostic criteria for cholangitis/cholecystitis. Once the diagnosis has been confirmed, initial medical treatment should be started immediately, severity should be assessed according to the severity grading criteria for acute cholangitis/cholecystitis, and the patient's general status should be evaluated. For mild acute cholangitis, in most cases initial treatment including antibiotics is sufficient, and most patients do not require biliary drainage. However, biliary drainage should be considered if a patient does not respond to initial treatment. For moderate acute cholangitis, early endoscopic or percutaneous transhepatic biliary drainage is indicated. If the underlying etiology requires treatment, this should be provided after the patient's general condition has improved; endoscopic sphincterotomy and subsequent choledocholithotomy may be performed together with biliary drainage. For severe acute cholangitis, appropriate respiratory/circulatory management is required. Biliary drainage should be performed as soon as possible after the patient's general condition has been improved by initial treatment and respiratory/circulatory management. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.
Effects of rumen‐protected pantothenate supplementation on lactation performance, ruminal fermentation, nutrient digestion and blood metabolites in dairy cows
Authors: Wang Cong , Liu Qiang , Li He Qiong , Wu Xiao Xu , Guo Gang , Huo Wen Jie , Pei Cai Xia , Zhang Yan Li , Zhang Shuan Lin
Published: September 2017

BACKGROUND

Lactation performance of dairy cow has considerably increased with animal breeding and management improvement in recent years. Ruminal net synthesised pantothenic acid is insufficient to meet the requirement of high producing dairy cows. The objective was to investigate the effects of rumen‐protected pantothenate (RPP) on lactation performance, ruminal fermentation, nutrient digestion and blood metabolites in dairy cows.

RESULTS

Dry matter (DM) intake tended to increase, whereas milk yields, milk fat percentage and yield, body condition score (BCS) changes and net energy output except for maintenance increased linearly with increasing RPP supplementation. Ruminal pH and ammonia N concentration tended to decrease, total VFA tended to increase, while acetate‐to‐propionate ratio increased linearly with increasing RPP supplementation. Digestibilities of DM, organic matter and crude protein increased linearly, but neutral detergent fibre and acid detergent fibre digestibility tended to increase. Blood glucose, total protein, non‐esterified fatty acids, pantothenic acid, pantothenate kinase, succinyl CoA, acyl carrier protein and acetyl CoA also increased linearly with increasing RPP supplementation.

CONCLUSION

The results indicated that supplementary RPP improved lactation performance, nutrient digestion and blood parameters in a dose‐dependent manner, and the optimal dose was 12 g RPP per cow per day in the current study. © 2017 Society of Chemical Industry
Migration modelling of phthalate from non‐alcoholic beer bottles by adaptive neuro‐fuzzy inference system
Authors: Rafiei Nazari Roshanak , Noorian Simin , Arabameri Majid
Published: September 2017

BACKGROUND

There are limitations to the basic knowledge regarding various ways by which packaging components migrate into food as well as ways by which various conditions, elements and molecules related to this phenomenon are analysed. This research aimed to model phthalate migration from polyethylene terephthalate bottles containing non‐alcoholic beer by performing adaptive neuro‐fuzzy inference system (ANFIS) analysis.

RESULTS

The data showed that storage temperature, contact surface and storage period correlates with the rate of migration. Migration of phthalate increases with storage duration gradually and reduces under different temperatures and contact surface. Moreover, increased temperature and storage duration resulted in an increase in migration level ranging from 0.6 μg L−1 to 2.9 μg L−1. In summary, the present study used an ANFIS architecture which consists of three inputs (temperature, surface and storage period), Gauss‐bell membership functions for each input variable and one output layer, which represent the migration level. The validation and training models showed an excellent match between the experimental and predicted values of ANFIS.

CONCLUSION

Analysis of the model showed that ANFIS is a powerful tool for predicting phthalate migration from bottles containing non‐alcoholic beer. © 2017 Society of Chemical Industry
Investigating the uptake and acquisition of potentially toxic elements in plants and health risks associated with the addition of fresh biowaste amendments to industrially contaminated soil
Authors: Yousaf Balal , Liu Guijian , Abbas Qumber , Wang Ruwei , Imtiaz Muhammad , Zia‐ur‐Rehman Muhammad
Published: September 2017

Soil contamination by potentially toxic elements (PTEs), due to rapid industrialization and urbanization, is a serious environmental concern that has been threatening both the sustainability of various agroecosystems and human health. Efforts to investigate the bioavailability, transfer, and accumulation of PTEs in the soil–plant system and their possible health consequences have almost exclusively focused in the past studies. However, there is limited evidence for increased human exposure to PTEs through dietary intake of food crop grown on contaminated soil influenced by fresh biowaste amendments (FBAs). Here, we show that FBAs addition to soil markedly (p ≤ .01) intensified human exposure to PTEs through impacts on solubility, uptake, and bioaccumulation compared with the control. In general, the risk assessment performed indicated that the hazard index values for FBAs treatments were notably higher than that of control; however, these were shown to be less than the legal limit (<1). In addition, the lifetime risks of developing carcinogenicity from exposure to PTEs were far above the maximum regulatory limits (1.00E‐06), indicating that remarkable (p ≤ .01) amount of PTEs was transferred to food with the addition of FBAs. Conclusively, these results suggest that the use of FBAs to contaminated soil aggravates health risks of PTEs through wheat consumption. Further studies, which incorporate the in vitro gastrointestinal bioaccessibility, should be conducted to heighten our understanding about PTEs exposure and the risks associated with FBAs addition to contaminated soil.
Grazing enhances soil nutrient effects: Trade‐offs between aboveground and belowground biomass in alpine grasslands of the Tibetan Plateau
Authors: Sun Jian , Ma Baibing , Lu Xuyang
Published: September 2017

Understanding the impact of grazing patterns on grassland production is of fundamental importance for grassland conservation and management. The objective of this study is to obtain an understanding of the trade‐offs between aboveground biomass and belowground biomass, which are influenced by environmental factors in free grazing (FG) and grazing exclusion (GE) alpine grasslands on the Tibetan Plateau. We explored the relationships between the trade‐off and environmental factors using correlation analysis, a generalized additive model and a structural equation model, and then found that the key factors that determine trade‐off showed differences in FG and GE grasslands and that the final structural equation modeling result explained that 96% (path coefficient = 0.96) and 65% (path coefficient = 0.65) of the variations in the trade‐off were due to FG or GE classifications, respectively. The results demonstrated that soil organic carbon, soil carbon/soil nitrogen, and soil available nitrogen affect the trade‐off between aboveground and belowground biomass in FG grasslands more obviously than in GE grasslands. However, the effects of growing season temperature on the trade‐off were insignificant, −0.218 and −0.181 in FG and GE grasslands, respectively. FG increased the soil bulk density, which resulted in an alteration in the soil pore size distribution and a greater resistance to root penetration. In addition, FG affected the level of soil nutrition, which will affect the nitrogen mineralization of decomposition and absorption, as well as the root biomass. Consequently, this study can provide guidance to improve the quality of grassland.
Model‐based exploration of hydrological connectivity and solute transport in a forested hillslope
Authors: Laine‐Kaulio Hanne , Koivusalo Harri
Published: September 2017

Preferential flowpaths control hydrological connectivity in forested hillslopes. However, current understanding on the nature, extent, and impacts of hydrological connectivity within hillslopes is still limited. Distributed 2‐pore domain models of subsurface water flow and solute transport in and between the preferential flowpaths and the soil matrix provide applicable means to investigate the connectivity. We identified possible (dis)connections of preferential flowpaths in a forested hillslope section from dye tracer data and incorporated them in a 3D 2‐pore domain model; the model was run and evaluated against ion tracer data. The objectives were to explore hydrological connectivity within the hillslope and quantify its impacts on solute transport. The main control for capturing the internal concentration dynamics of the ion‐tracer plume with the model was an explicit description of local disconnections of preferential flowpaths in the form of local reductions in their hydraulic conductivity. Continuous preferential flowpaths were formed by rooting activities, erosion caused by subsurface flow, freezing–thawing cycles, and soil fauna, but they were locally disconnected by, for example, cemented soil material. As a result, the dominant lateral flowpath was tortuous, and tracer transport within this pathway was highly preferential: Compared to earlier models without flowpath disconnections, increase in the average lateral tracer load was 1.7‐fold and in the maximum load 7.9‐fold. The results indicate that the volume and hydraulic conductivity of the actual, connected preferential flowpaths control, in combination with linkages between preferential flowpaths and soil matrix, pollutant transport in forested hillslopes.
Characterization of the diffusion coefficient of blood
Authors: Funck Carsten , Laun Frederik Bernd , Wetscherek Andreas
Published: September 2017

Purpose

To characterize the diffusion coefficient of human blood for accurate results in intravoxel incoherent motion imaging.

Methods

Diffusion‐weighted MRI of blood samples from 10 healthy volunteers was acquired with a single‐shot echo‐planar‐imaging sequence at body temperature. Effects of gradient profile (monopolar or flow‐compensated), diffusion time (40–100 ms), and echo time (60–200 ms) were investigated.

Results

Although measured apparent diffusion coefficients of blood were larger for flow‐compensated than for monopolar gradients, no dependence of the apparent diffusion coefficient on the diffusion time was found. Large differences between individual samples were observed, with results ranging from 1.26 to 1.66 µm2/ms for flow‐compensated and 0.94 to 1.52 µm2/ms for monopolar gradients. Statistical analysis indicates correlations of the flow‐compensated apparent diffusion coefficient with hematocrit (P = 0.007) and hemoglobin (P = 0.017), but not with mean corpuscular volume (P = 0.64). Results of Monte‐Carlo simulations support the experimental observations.

Conclusions

Measured blood apparent diffusion coefficient values depend on hematocrit/hemoglobin concentration and applied gradient profile due to non‐Gaussian diffusion. Because in vivo measurement is delicate, an estimation based on blood count results could be an alternative. For intravoxel incoherent motion modeling, the use of a blood self‐diffusion constant Db = 1.54 ± 0.12 µm2/ms for flow‐compensated and Db = 1.30 ± 0.18 µm2/ms for monopolar encoding is suggested. Magn Reson Med 79:2752–2758, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Recurrent desmoplastic small round cell tumor responding to an mTOR inhibitor containing regimen
Authors: Tarek Nidale , Hayes‐Jordan Andrea , Salvador Laura , McAleer Mary F. , Herzog Cynthia E. , Huh Winston W.
Published: September 2017

Desmoplastic small round cell tumor (DSRCT) is a rare mesenchymal tumor that typically presents with multiple abdominal masses. Initial treatment is multimodal in nature. Patients with relapsed DSRCT have a poor prognosis, and there are no standard therapies. We report our experience with five patients treated with vinorelbine, cyclophosphamide, and temsirolimus (VCT). Median number of VCT courses delivered was 7 (range 4–14 courses), and partial response was observed in all patients. Median time to progression or relapse was 8.5 months (range 7–16 months). Neutropenia and mucositis were most common toxicities (n = 4 each).