bluuebunny/crossref_metadata_2025 huggingface dataset:
The genetic landscape of familial congenital hydrocephalus
Authors: Shaheen Ranad , Sebai Mohammed Adeeb , Patel Nisha , Ewida Nour , Kurdi Wesam , Altweijri Ikhlass , Sogaty Sameera , Almardawi Elham , Seidahmed Mohammed Zain , Alnemri Abdulrahman , Madirevula Sateesh , Ibrahim Niema , Abdulwahab Firdous , Hashem Mais , Al‐Sheddi Tarfa , Alomar Rana , Alobeid Eman , Sallout Bahauddin , AlBaqawi Badi , AlAali Wajeih , Ajaji Nouf , Lesmana Harry , Hopkin Robert J. , Dupuis Lucie , Mendoza‐Londono Roberto , Al Rukban Hadeel , Yoon Grace , Faqeih Eissa , Alkuraya Fowzan S.
Published: May 2017

Objective

Congenital hydrocephalus is an important birth defect, the genetics of which remains incompletely understood. To date, only 4 genes are known to cause Mendelian diseases in which congenital hydrocephalus is the main or sole clinical feature, 2 X‐linked (L1CAM and AP1S2) and 2 autosomal recessive (CCDC88C and MPDZ). In this study, we aimed to determine the genetic etiology of familial congenital hydrocephalus with the assumption that these cases represent Mendelian forms of the disease.

Methods

Exome sequencing combined, where applicable, with positional mapping.

Results

We identified a likely causal mutation in the majority of these families (21 of 27, 78%), spanning 16 genes, none of which is X‐linked. Ciliopathies and dystroglycanopathies were the most common etiologies of congenital hydrocephalus in our cohort (19% and 26%, respectively). In 1 family with 4 affected members, we identified a homozygous truncating variant in EML1, which we propose as a novel cause of congenital hydrocephalus in addition to its suggested role in cortical malformation. Similarly, we show that recessive mutations in WDR81, previously linked to cerebellar ataxia, mental retardation, and disequilibrium syndrome 2, cause severe congenital hydrocephalus. Furthermore, we confirm the previously reported candidacy of MPDZ by presenting a phenotypic spectrum of congenital hydrocephalus associated with 5 recessive alleles.

Interpretation

Our study highlights the importance of recessive mutations in familial congenital hydrocephalus and expands the locus heterogeneity of this condition. Ann Neurol 2017;81:890–897
Sodium intake and multiple sclerosis activity and progression in BENEFIT
Authors: Fitzgerald Kathryn C. , Munger Kassandra L. , Hartung Hans‐Peter , Freedman Mark S. , Montalbán Xavier , Edan Gilles , Wicklein Eva‐Maria , Radue Ernst‐Wilhelm , Kappos Ludwig , Pohl Christoph , Ascherio Alberto ,   for the BENEFIT Study Group
Published: May 2017

Objective

To assess whether a high‐salt diet, as measured by urinary sodium concentration, is associated with faster conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and MS activity and disability.

Methods

BENEFIT was a randomized clinical trial comparing early versus delayed interferon beta‐1b treatment in 465 patients with a CIS. Each patient provided a median of 14 (interquartile range = 13–16) spot urine samples throughout the 5‐year follow‐up. We estimated 24‐hour urine sodium excretion level at each time point using the Tanaka equations, and assessed whether sodium levels estimated from the cumulative average of the repeated measures were associated with clinical (conversion to MS, Expanded Disability Status Scale [EDSS]) and magnetic resonance imaging (MRI) outcomes.

Results

Average 24‐hour urine sodium levels were not associated with conversion to clinically definite MS over the 5‐year follow‐up (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.67–1.24 per 1g increase in estimated daily sodium intake), nor were they associated with clinical or MRI outcomes (new active lesions after 6 months: HR = 1.05, 95% CI = 0.97–1.13; relative change in T2 lesion volume: −0.11, 95% CI = −0.25 to 0.04; change in EDSS: −0.01, 95% CI = −0.09 to 0.08; relapse rate: HR = 0.78, 95% CI = 0.56–1.07). Results were similar in categorical analyses using quintiles.

Interpretation

Our results, based on multiple assessments of urine sodium excretion over 5 years and standardized clinical and MRI follow‐up, suggest that salt intake does not influence MS disease course or activity. Ann Neurol 2017;82:20–29
Differential neuronal susceptibility and apoptosis in congenital Zika virus infection
Authors: Ho Cheng‐Ying , Ames Heather M. , Tipton Ashley , Vezina Gilbert , Liu Judy S. , Scafidi Joseph , Torii Masaaki , Rodriguez Fausto J. , du Plessis Adre , DeBiasi Roberta L.
Published: May 2017

To characterize the mechanism of Zika virus (ZIKV)‐associated microcephaly, we performed immunolabeling on brain tissue from a 20‐week fetus with intrauterine ZIKV infection. Although ZIKV demonstrated a wide range of neuronal and non‐neuronal tropism, the infection rate was highest in intermediate progenitor cells and immature neurons. Apoptosis was observed in both infected and uninfected bystander cortical neurons, suggesting a role for paracrine factors in induction of neuronal apoptosis. Our results highlight differential neuronal susceptibility and neuronal apoptosis as potential mechanisms in the development of ZIKV‐associated microcephaly, and may provide insights into the design and best timing of future therapy. Ann Neurol 2017;82:121–127
Isomerisierung, Ringerweiterungs‐ und Ringverengungsreaktionen von 1,3‐Diphosphet‐Komplexen
Authors: Rummel Eva‐Maria , Balázs Gábor , Heinl Veronika , Scheer Manfred
Published: May 2017

Reaktionen zwischen dem 1,3‐Diphosphet‐Komplex [Cp′′′Co(η4‐P2C2tBu2)] (1) und Ag[Al{OC(CF3)3}4] (Ag[pftb]) wurden unter verschiedenen Bedingungen durchgeführt. In CH2Cl2 konnte das 1,2‐Diphosphet‐Isomerisierungsprodukt [Ag2{Cp′′′Co(μ,η4:η1:η1‐1,2‐P2C2tBu2)}2{Cp′′′Co(μ,η4:η1‐1,2‐P2C2tBu2)}2]⋅2[pftb] (2) isoliert werden. In Diffusionsexperimenten von 1 in n‐Hexan und Ag[pftb] in CH2Cl2, wurden der Triphosphacobaltocenium‐Komplex [Cp′′′Co(η5‐P3C2tBu2)][pftb] (4) und der Phosphirenylium‐Komplex [Cp′′′Co(η3‐PC2tBu2)][pftb] (5) über eine Ringerweiterung bzw. Ringverengung erhalten. Darüber hinaus wurde durch Hinzugabe von Pyridin zum Ag‐Komplex 2 der 1,2‐Diphosphet‐Komplex [Cp′′′Co(η4‐1,2‐P2C2tBu2)] (3) freigesetzt. Ebenfalls zeigte sich, dass die Bildung von 3 durch Thermolyse von 1 möglich ist, was eine aussichtsreiche Methode für solche Isomerisierungen repräsentiert. 1,2‐Diphosphet‐Komplexe wie 3 sind thermodynamisch stabiler, aber schwerer zu synthetisieren als die 1,3‐Isomere.
Role of poly(2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid) in the modification of polysulfone membranes for ultrafiltration
Authors: Singh Randeep , Purkait Mihir Kumar
Published: May 2017

In this study polysulfone membranes with antifouling and hydrophilic properties were synthesized using poly(2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid) (AMPS) as an additive for the first time. Different wt % of AMPS was used to prepare polysulfone membranes by phase inversion method. The role of AMPS on the porosity, pore size distribution, hydrophilicity, and antifouling nature was investigated and analyzed in detail. Characterization techniques like field emission scanning electron microscope, atomic force microscopy, and imageJ software were used to characterize the morphology of prepared membranes. There is positive effect of the additive addition on all the membrane parameters like Pure water flux [101.76 L/(m2 h)] (MR0) to 464.06 L/(m2 h) (MR4)], hydraulic permeability [0.65 (MR0) to 2.01 (MR4)], equilibrium water content [21.74 (MR0) to 71.45 (MR4)], and porosity [0.024 (MR0) to 0.58 (MR4)]. Response surface methodology was used for the optimization of bovine serum albumin (BSA) flux and rejection. The results of the morphological as well as permeation studies depicted that permeate flux and antifouling nature were increased with the amount of AMPS present in the membrane matrix. The antifouling study of the prepared membranes was undertaken by using BSA solution of 1000 mg/L. Positive results were seen with the increase in amount of AMPS, since, the total membrane resistance has been decreased from 0.95 (MR0) to 0.74 (MR4). Separation of humic acid from aqueous medium was also performed with the best performing membrane (MR4, having the highest amount of AMPS). Separation efficiency of 100% and 94% were obtained using 10 mg/L and 50 mg/L of HA, respectively. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45290.
Restoring Maximum Vertical Browsing Reach in Sauropod Dinosaurs
Authors: PAUL GREGORY S.
Published: May 2017

The ongoing controversy centered on neck posture and function in sauropod dinosaurs is misplaced for a number of reasons. Because of an absence of pertinent data it is not possible to accurately restore the posture and range of motion in long necked fossil animals, only gross approximations are possible. The existence of a single “neutral posture” in animals with long, slender necks may not exist, and its relationship to feeding habits is weak. Restorations of neutral osteological neck posture based on seemingly detailed diagrams of cervical articulations are not reliable because the pictures are not sufficiently accurate due to a combination of illustration errors, and distortion of the fossil cervicals. This is all the more true because fossil cervical series lack the critical inter‐centra cartilage. Maximum vertical reach is more readily restorable and biologically informative for long necked herbivores. Modest extension of 10° between each caudal cervical allowed high shouldered sauropods to raise the cranial portion of their necks to vertical postures that allowed them to reach floral resources far higher than seen in the tallest mammals. This hypothesis is supported by the dorsally extended articulation of the only known co‐fused sauropod cervicals. Many sauropods appear to have been well adapted for rearing in order to boost vertical reach, some possessed retroverted pelves that may have allowed them to walk slowly while bipedal. A combination of improved high browsing abilities and sexual selection probably explains the unusually long necks of tall ungulates and super tall sauropods. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1802–1825, 2017. © 2017 Wiley Periodicals, Inc.
An analysis of 14 Million tweets on hashtag‐oriented spamming*
Authors: Sedhai Surendra , Sun Aixin
Published: May 2017

Over the years, Twitter has become a popular platform for information dissemination and information gathering. However, the popularity of Twitter has attracted not only legitimate users but also spammers who exploit social graphs, popular keywords, and hashtags for malicious purposes. In this paper, we present a detailed analysis of the HSpam14 dataset, which contains 14 million tweets with spam and ham (i.e., nonspam) labels, to understand spamming activities on Twitter. The primary focus of this paper is to analyze various aspects of spam on Twitter based on hashtags, tweet contents, and user profiles, which are useful for both tweet‐level and user‐level spam detection. First, we compare the usage of hashtags in spam and ham tweets based on frequency, position, orthography, and co‐occurrence. Second, for content‐based analysis, we analyze the variations in word usage, metadata, and near‐duplicate tweets. Third, for user‐based analysis, we investigate user profile information. In our study, we validate that spammers use popular hashtags to promote their tweets. We also observe differences in the usage of words in spam and ham tweets. Spam tweets are more likely to be emphasized using exclamation points and capitalized words. Furthermore, we observe that spammers use multiple accounts to post near‐duplicate tweets to promote their services and products. Unlike spammers, legitimate users are likely to provide more information such as their locations and personal descriptions in their profiles. In summary, this study presents a comprehensive analysis of hashtags, tweet contents, and user profiles in Twitter spamming.
Strategies for Efficient Solar Water Splitting Using Carbon Nitride
Authors: Yang Yilong , Wang Songcan , Li Yongli , Wang Jinshu , Wang Lianzhou
Published: May 2017

Graphitic carbon nitride (g‐C3N4)‐based photocatalysts are promising for photocatalytic water splitting to produce clean solar fuels due to their low cost, suitable band structure and excellent photocatalytic performance. This review focuses on the state‐of‐the‐art progress of the strategies for modifying g‐C3N4‐based photocatalysts toward efficient photocatalytic water splitting. In particular, we highlight the importance of interfacial engineering and nanostructural control to facilitating charge separation and migration. Other strategies including doping and defect engineering are also concisely discussed. Finally, the perspectives on the challenges and future development of g‐C3N4‐based photocatalysts are presented.
Retracted: Studies on the luminescence properties of cerium co‐doping on Ca2MgSi2O7:Eu2+ phosphor by solid‐state reaction method
Authors: Sahu Ishwar Prasad , Bisen D. P. , Murthy K. V. R. , Tamrakar R. K.
Published: May 2017

Ca2MgSi2O7:Ce3+, Ca2MgSi2O7:Eu2+ and Ca2MgSi2O7:Eu2+,Ce3+ phosphors were prepared using the solid‐state reaction method. The crystal structures of the sintered phosphors were of melilite type, which has a tetragonal crystallography. The chemical compositions of the sintered phosphors was confirmed by energy dispersive X‐ray spectroscopy. The different thermoluminescence kinetic parameters [activation energy (E), frequency factor (s) and order of the kinetics (b)] of these phosphors were evaluated and compared using the peak shape method. Under ultraviolet excitation, the emission spectra of both Ca2MgSi2O7:Eu2+ and Ca2MgSi2O7:Eu2+,Ce3+ phosphors were composed of a broad emission band peaking at 530 nm. When the Ca2MgSi2O7:Eu2+ phosphor is co‐doped with Ce3+ ions, photoluminescence, afterglow and mechanoluminescence intensity was strongly enhanced. Ca2MgSi2O7:Eu2+ showed some afterglow with a short persist time. On incorporation of Ce3+, efficient energy transfer from Ce3+ to Eu2+ was found and the emission intensity of Eu2+ was enhanced. The mechanoluminescence intensities of Ca2MgSi2O7:Ce3+, Ca2MgSi2O7:Eu2+ and Ca2MgSi2O7:Eu2+,Ce3+ phosphors increased proportionally increased with the increase in impact velocity, which suggests that these phosphors can be used as sensors to detect stress in an object.
Design and chemical syntheses of potent matriptase‐2 inhibitors based on trypsin inhibitor SFTI‐1 isolated from sunflower seeds
Authors: Gitlin‐Domagalska Agata , Dębowski Dawid , Łęgowska Anna , Stirnberg Marit , Okońska Joanna , Gütschow Michael , Rolka Krzysztof
Published: May 2017

Matriptase‐2 plays a pivotal role in keeping iron concentrations within a narrow physiological range in humans. The opportunity to reduce matriptase‐2 proteolytic activity may open a novel possibility to treat iron overload diseases, such as hereditary hemochromatosis and thalassemia. Here, we present 23 new analogues of trypsin inhibitor SFTI‐1 designed to inhibit human matriptase‐2. Influence of the modifications Gly1Lys, Ile10Arg, and Phe12His, as well as the introduction of Narg in P1 or P1 and P4 positions were examined. Selected peptides were further analyzed, together with previously reported peptides, for their inhibitory activity against related human proteases, that are, matriptase‐1, plasmin, thrombin and trypsin. A highly potent inhibitor of matriptase‐2, the bicycylic [Arg5, Arg10, His12]SFTI‐1, with aKivalue of 15 nmwas obtained.
A review of chromatographic methods for ketamine and its metabolites norketamine and dehydronorketamine
Authors: Göktaş Eylem Funda , Arıöz Filiz
Published: May 2017

Ketamine has a synthetic, sedative, nonbarbiturate and fast‐acting anaesthetic properties and it is commonly used in both humans and veterinary surgery. There are many analytical methods available for the qualitative and quantitative determination of ketamine and its metabolites. We have focused on sample pre‐treatment and chromatographic techniques used since the year 2000 for the determination of ketamine and its metabolites in biological samples. Liquid and gas chromatography coupled with various detection techniques (mass spectrometry, ultraviolet or fluorescence detection) have been used in these publications. This review gives information on the implementation of methods for studying ketamine and its metabolites in various research applications. It could be useful in forensic sciences including doping control and also in the therapeutic drug monitoring of ketamine and norketamine in human and animal clinical surgery.
Measuring the aggregation of CHO cells prior to single cell cloning allows a more accurate determination of the probability of clonality
Authors: Klottrup Kerensa J. , Miro‐Quesada Guillermo , Flack Layla , Pereda Ivan , Hawley‐Nelson Pamela
Published: May 2017

The manufacturing process for biotherapeutics is closely regulated by the Food and Drug Administration (FDA), European Medicines Agency (EMA) and other regulatory agencies worldwide. To ensure consistency of the product of a manufacturing cell line, International Committee on Harmonization guidelines (Q5D, 1997) state that the cell substrate should be derived from a single cell progenitor, i.e., clonal.Cell lines in suspension culture may naturally revert to cell adhesion in the form of doublets, triplets and higher order structures of clustered cells. We can show evidence of a single colony from limiting dilution cloning or in semi‐solid media, but we cannot determine the number of cells from which the colony originated. To address this, we have used the ViCELL® XR (Beckman Coulter, High Wycombe, UK) cell viability analyzer to determine the proportion of clusters of two or more cells in a sample of the cell suspension immediately prior to cloning. Here, we show data to define the accuracy of the ViCELL for characterizing a cell suspension and summarize the statistical model combining two or more rounds of cloning to derive the probability of clonality. The resulting statistical model is applied to cloning in semi‐solid medium, but could equally be applied to a limiting dilution cloning process. We also describe approaches to reduce cell clusters to generate a cell line with a high probability of clonality from a CHO host lineage. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:593–601, 2018
Enhanced process understanding and multivariate prediction of the relationship between cell culture process and monoclonal antibody quality
Authors: Sokolov Michael , Ritscher Jonathan , MacKinnon Nicola , Souquet Jonathan , Broly Hervé , Morbidelli Massimo , Butté Alessandro
Published: May 2017

This work investigates the insights and understanding which can be deduced from predictive process models for the product quality of a monoclonal antibody based on designed high‐throughput cell culture experiments performed at milliliter (ambr‐15®) scale. The investigated process conditions include various media supplements as well as pH and temperature shifts applied during the process. First, principal component analysis (PCA) is used to show the strong correlation characteristics among the product quality attributes including aggregates, fragments, charge variants, and glycans. Then, partial least square regression (PLS1 and PLS2) is applied to predict the product quality variables based on process information (one by one or simultaneously). The comparison of those two modeling techniques shows that a single (PLS2) model is capable of revealing the interrelationship of the process characteristics to the large set product quality variables. In order to show the dynamic evolution of the process predictability separate models are defined at different time points showing that several product quality attributes are mainly driven by the media composition and, hence, can be decently predicted from early on in the process, while others are strongly affected by process parameter changes during the process. Finally, by coupling the PLS2 models with a genetic algorithm first the model performance can be further improved and, most importantly, the interpretation of the large‐dimensioned process–product‐interrelationship can be significantly simplified. The generally applicable toolset presented in this case study provides a solid basis for decision making and process optimization throughout process development. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1368–1380, 2017
In vitro methanol production from methyl coenzyme M using the Methanosarcina barkeri MtaABC protein complex
Authors: Dong Ming , Gonzalez Tara D. , Klems Meghan M. , Steinberg Lisa M. , Chen Wilfred , Papoutsakis Eleftherios T. , Bahnson Brian J.
Published: May 2017

Methanol:coenzyme M methyltransferase is an enzyme complex composed of three subunits, MtaA, MtaB, and MtaC, found in methanogenic archaea and is needed for their growth on methanol ultimately producing methane. MtaABC catalyzes the energetically favorable methyl transfer from methanol to coenzyme M to form methyl coenzyme M. Here we demonstrate that this important reaction for possible production of methanol from the anaerobic oxidation of methane can be reversed in vitro. To this effect, we have expressed and purified the Methanosarcina barkeri MtaABC enzyme, and developed an in vitro functional assay that demonstrates MtaABC can catalyze the energetically unfavorable (ΔG° = 27 kJ/mol) reverse reaction starting from methyl coenzyme M and generating methanol as a product. Demonstration of an in vitro ability of MtaABC to produce methanol may ultimately enable the anaerobic oxidation of methane to produce methanol and from methanol alternative fuel or fuel‐precursor molecules. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1243–1249, 2017
Media development for large scale Agrobacterium tumefaciens culture
Authors: Leth Ingrid K. , McDonald Karen A.
Published: May 2017

A chemically defined media was developed for growing Agrobacterium tumefaciens at large scale for commercial production of recombinant proteins by transient expression in plants. Design of experiments was used to identify major and secondary effects of ten media components: sucrose, ammonium sulfate ((NH4)2SO4), magnesium sulfate heptahydrate (MgSO4*7H2O), calcium chloride dihydrate (CaCl2*2H2O), iron (II) sulfate heptahydrate (FeSO4*7H2O), manganese (II) sulfate monohydrate (MnSO4*H2O), zinc sulfate heptahydrate (ZnSO4*7H2O), sodium chloride (NaCl), potassium chloride (KCl) and a sodium/potassium phosphate buffer (Na2HPO4/KH2PO4). Calcium and zinc were found to have no detectable impact on biomass concentration or transient expression level, and concentrations of the other components that maximized final biomass concentration were determined. The maximum specific growth rate of Agrobacterium strain C58C1 pTFS40 in this media was 0.33 ± 0.01 h−1 and the final biomass concentration after 26 h of batch growth in shake flasks was 2.6 g dry cell weight/L. Transient expression levels of the reporter protein GUS following infiltration of a recombinant Agrobacterium strain C58C1 into N. benthamiana were comparable when the strain was grown in the defined media, Lysogeny Broth (LB) media, or yeast extract‐peptone (YEP) media. In LB and YEP media, free amino acid concentration was measured at three points over the course of batch growth of Agrobacterium strain C58C1 pTFS40; results indicated that l‐serine and l‐asparagine were depleted from the media first, followed by l‐alanine and l‐glutamic acid. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1218–1225, 2017
Improving the production, activity, and stability of CLEAs with diepoxides
Authors: Hernández‐García Samanta , García‐García María Inmaculada , García‐Carmona Francisco
Published: May 2017

Among enzyme immobilization techniques, the preparation of cross‐linked enzyme aggregates has shown promising results in biocatalysis, because they are easy to prepare, versatile, and cheap. The method involves the precipitation of enzymes with ammonium sulfate or an organic solvent and subsequent cross‐linking with glutaraldehyde. However, the Schiff base produced with glutaraldehyde is reversible and can be broken with acids or bases, releasing proteins to the reaction medium. To solve this problem, we propose replacing glutaraldehyde with diepoxide compounds to obtain an irreversible secondary amine bond. Such a substitution avoids protein leakage during the biocatalytic process, contamination of the final products, and loss of enzyme. It also improves the synthesis of the biocatalyst, because, while the Schiff base is favored at mildly acidic pH, the epoxide reaction can be made at the optimal enzyme pH, assuring its structural stability and catalytic performance. The proposed method has been successfully used in the production and optimization of aldolase epoxy‐cross‐linked aggregates, which retain 98% activity. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1425–1429, 2017
Enhanced expression of cysteine‐rich antimicrobial peptide snakin‐1 in Escherichia coli using an aggregation‐prone protein coexpression system
Authors: Kuddus Md. Ruhul , Yamano Megumi , Rumi Farhana , Kikukawa Takashi , Demura Makoto , Aizawa Tomoyasu
Published: May 2017

Snakin‐1 (SN‐1) is a cysteine‐rich plant antimicrobial peptide and the first purified member of the snakin family. SN‐1 shows potent activity against a wide range of microorganisms, and thus has great biotechnological potential as an antimicrobial agent. Here, we produced recombinant SN‐1 in Escherichia coli by a previously developed coexpression method using an aggregation‐prone partner protein. Our goal was to increase the productivity of SN‐1 via the enhanced formation of insoluble inclusion bodies in E. coli cells. The yield of SN‐1 by the coexpression method was better than that by direct expression in E. coli cells. After refolding and purification, we obtained several milligrams of functionally active SN‐1, the identity of which was verified by MALDI‐TOF MS and NMR studies. The purified recombinant SN‐1 showed effective antimicrobial activity against test organisms. Our studies indicate that the coexpression method using an aggregation‐prone partner protein can serve as a suitable expression system for the efficient production of functionally active SN‐1. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1520–1528, 2017
Traumatic globe rupture after deep anterior lamellar keratoplasty—A novel management technique
Authors: Fiorentzis Miltiadis , Bäurle Sebastian , Viestenz Anja , Seitz Berthold , Viestenz Arne
Published: May 2017

A traumatic wound dehiscence can occur many years after surgery in 2–6% of all keratoplasties. Intraocular tissue prolapse can lead to severe visual loss. Deep anterior lamellar keratoplasty (DALK) leads to higher wound stability because of the intact Descemet membrane. We report a case of a novel management of wound dehiscence following DALK. A 59‐year‐old patient underwent uncomplicated DALK for advanced keratoconus. Eighteen months later he experienced a traumatic wound dehiscence (globe rupture) after a fall. Visual acuity decreased to light perception on the affected eye, the iris and prolapsed vitreous were incarcerated, and no retinal details were recognizable. The corneal graft was dehiscent over eight clock hours, the Descemet membrane was ruptured, and the stroma dissolved over 30% of its surface in a bell shape. Primary wound closure was performed with nylon 10‐0 single interrupted corneal sutures. One day after emergency treatment, a 23‐gauge pars‐plana‐vitrectomy for vitreous hemorrhage was conducted and a retinal tear was treated with laser photocoagulation. The Descemet membrane was repositioned using a 23 g vitrectomy probe under air and the globe was filled with SF6 gas. Postoperatively, visual acuity increased to 6/15 and the cornea cleared up. Corneal graft and Descemet membrane repositioning after trauma can avoid a further keratoplasty and the risk of immunological rejection of donor endothelial cells. Clin. Anat. 31:56–59, 2018. © 2017 Wiley Periodicals, Inc.
Ultrasonography‐driven combination antibiotic therapy with tigecycline significantly increases survival among patients with neutropenic enterocolitis following cytarabine‐containing chemotherapy for the remission induction of acute myeloid leukemia
Authors: Pugliese Novella , Salvatore Paola , Iula Dora Vita , Catania Maria Rosaria , Chiurazzi Federico , Della Pepa Roberta , Cerchione Claudio , Raimondo Marta , Giordano Claudia , Simeone Luigia , Caruso Simona , Pane Fabrizio , Picardi Marco
Published: May 2017

Neutropenic enterocolitis (NEC) is an abdominal infection reported primarily in patients with acute myeloid leukemia (AML) following chemotherapy, especially cytarabine, a notable efficacious cytotoxic agent for AML remission. Specific data regarding the impact of different cytarabine schedules and/or antibacterial regimens for NEC are sparse. The aim of the study was to identify the predictors of outcome within 30 days of NEC onset. NEC episodes were retrospectively pinpointed among 440 patients with newly diagnosed AML hospitalized in our Institution, over a 10‐year period, for receiving chemotherapy protocols with 100–6000 mg/m2 daily of cytarabine. Two subgroups, survivors versus nonsurvivors, were compared by using logistic regression analysis. NEC was documented in 100 of 420 (23.8%) analyzed patients: 42.5% had received high‐dose cytarabine, whereas 19% and 15% intermediate‐dose and standard‐dose cytarabine, respectively (P < 0.001). The 30‐day NEC attributable mortality rate was 23%. In univariate analysis, antileukemic protocols containing robust dosages of cytarabine were significantly associated with high mortality (P < 0.001); whereas, standard‐dose cytarabine and prompt initiation (at the ultrasonographic appearance of intestinal mural thickening) of NEC therapy with antibiotic combinations including tigecycline were significantly associated with low mortality. In multivariate analysis, high‐dose cytarabine‐containing chemotherapy was the independent predictor of poor outcome (odds ratio [OR]: 0.109; 95% confidence interval [CI]: 0.032–0.364; P < 0.001), whereas ultrasonography‐driven NEC therapy with antibiotic regimens including tigecycline was associated with a favorable outcome (OR: 13.161; 95% CI: 1.587–109.17; P = 0.017). Chemotherapy schedules with robust dosages of cytarabine for AML remission are associated with a high rate of NEC incidence and attributable. Vigorous antibacterial therapy, triggered off pathologic ultrasonographic findings, with drug combinations which have broad antimicrobial coverage and good gut penetration, specifically those also including tigecycline, may be effective in improving 30‐day survival rate after NEC onset.
A three‐gene signature from protein–protein interaction network of LOXL2‐ and actin‐related proteins for esophageal squamous cell carcinoma prognosis
Authors: Zhan Xiu‐hui , Jiao Ji‐wei , Zhang Hai‐feng , Li Chun‐quan , Zhao Jian‐mei , Liao Lian‐di , Wu Jian‐yi , Wu Bing‐li , Wu Zhi‐yong , Wang Shao‐hong , Du Ze‐peng , Shen Jin‐hui , Zou Hai‐ying , Neufeld Gera , Xu Li‐yan , Li En‐min
Published: May 2017

Current staging is inadequate for predicting clinical outcome of esophageal squamous cell carcinoma (ESCC). Aberrant expression of LOXL2 and actin‐related proteins plays important roles in ESCC. Here, we aimed to develop a novel molecular signature that exceeds the power of the current staging system in predicting ESCC prognosis. We found that LOXL2 colocalized with filamentous actin in ESCC cells, and gene set enrichment analysis (GSEA) showed that LOXL2 is related to the actin cytoskeleton. An ESCC‐specific protein–protein interaction (PPI) network involving LOXL2 and actin‐related proteins was generated based on genome‐wide RNA‐seq in 15 paired ESCC samples, and the prognostic significance of 14 core genes was analyzed. Using risk score calculation, a three‐gene signature comprising LOXL2, CDH1, and FN1 was derived from transcriptome data of patients with ESCC. The high‐risk three‐gene signature strongly correlated with poor prognosis in a training cohort of 60 patients (P = 0.003). In mRNA and protein levels, the prognostic values of this signature were further validated in 243 patients from a testing cohort (P = 0.001) and two validation cohorts (P = 0.021, P = 0.007). Furthermore, Cox regression analysis revealed that the signature was an independent prognostic factor. Compared with using the signature or TNM stage alone, the combined model significantly enhanced the accuracy in evaluating ESCC prognosis. In conclusion, our data reveal that the tumor‐promoting role of LOXL2 in ESCC is mediated by perturbing the architecture of actin cytoskeleton through its PPIs. We generated a novel three‐gene signature (PPI interfaces) that robustly predicts poor clinical outcome in ESCC patients.
A state‐wide initiative to promote genetic testing in an underserved population
Authors: Underhill Meghan L. , Blonquist Traci M. , Habin Karleen , Lundquist Debra , Shannon Kristen , Robinson Kathryn , Woodford Mary‐Lou , Boucher Jean
Published: May 2017

Genetic testing for cancer susceptibility has been widely studied and utilized clinically. Access to genetic services in research and practice is largely limited to well‐insured, Caucasian individuals. In 2009, the Cancer Resource Foundation (CRF) implemented the Genetic Information for Treatment Surveillance and Support (GIFTSS) program to cover the out‐of‐pocket expenses associated with cancer genetic testing, targeting high‐risk individuals with limited financial means and limited health insurance coverage. Here, we (i) describe the characteristics of participants in the Massachusetts (MA) GIFTSS program and (ii) evaluate mutations found in this diverse sample. A secondary retrospective data analysis was performed using de‐identified demographic data obtained from laboratory requisition forms and cancer genetic testing result information from the laboratory source. Eligible participants were those who utilized the MA GIFFTS program from 2009 through December of 2014. Data were summarized using descriptive measures of central tendency. Participants were residents of Massachusetts who had health insurance and had a reported income within 250–400% of the federal poverty level. Genetic testing results were categorized following clinical guidelines. Overall, 123 (13%) of participants tested positive for a mutation in a cancer susceptibility gene. For those with a cancer diagnosis, 65 (12%) were found to have a positive result and 20 (7%) had a variant of uncertain significance (VUS). For those unaffected patients, 58 (15%) had a positive result and 10 (3%) were found to have a VUS. The results from this study are useful in describing genetic testing outcomes in this high‐risk underserved community. Repeatedly, the literature reports that individuals from diverse or limited resource settings are less likely to access genetic testing. Continued research efforts should be devoted to promoting the access of genetic testing in the high‐risk, underserved community.
Comparative molecular profiling of HPV‐induced squamous cell carcinomas
Authors: Koncar Robert F. , Feldman Rebecca , Bahassi El Mustapha , Hashemi Sadraei Nooshin
Published: May 2017

Approximately 5% of all cancer incidences result from human papillomavirus (HPV) infection. HPV infection most commonly leads to cancers of the anogenital region or oropharynx. It is unknown whether different HPV‐mediated cancers collectively share a molecular signature and it is important to determine if there are targetable alterations common to different types of HPV‐positive tumors. We analyzed 743 p53 wild‐type samples of anal, cervical, oropharyngeal, and vulvar squamous cell carcinomas which underwent multiplatform testing at a commercial molecular profiling service. Expression of 24 proteins was measured by immunohistochemistry (IHC), mutation of 48 genes was determined by next‐generation and Sanger sequencing, and copy number alteration for six genes was determined by in situ hybridization. The four cohorts had remarkably similar molecular profiles. No gene had a statistically significant difference in mutation frequency or copy number change between the four different types of squamous cell carcinomas. The only significant differences between cohorts were frequency of ERCC1 and SPARC loss as determined by IHC. In all four cancer types, oncogene mutation and PD‐L1 expression was relatively infrequent. The most commonly mutated gene was PIK3CA, with mutations most often affecting the helical domain of the protein and accompanied by concurrent lack of PTEN expression. Loss of MGMT and RRM1 was common among the four cohorts and may be predictive of response to cytotoxic therapies not currently being used to treat these cancer types. The similar molecular profiles of the four cohorts indicate that treatment strategies may be similarly efficacious across HPV‐positive cancers.
A New Anti‐Inflammatory Alkaloid from Roots of Heracleum dissectum
Authors: Zhang Hai‐Long , Wu Xin‐Yuan , Mi Jie , Peng Ya‐Jie , Wang Zhi‐Gang , Liu Ying , Wu Xiu‐Li , Gao Yang
Published: May 2017

Using various chromatographic methods, a new piperidinone alkaloid, (3S)‐3‐{4‐[(1E)‐3‐hydroxyprop‐1‐en‐1‐yl]‐2‐methoxyphenoxy}piperidin‐2‐one (1), together with 10 known compounds, bergapten (2), xanthotoxol (3), isopimpinellin (4), isobergapten (5), heratomol‐6‐O‐β‐d‐glucopyranoside (6), scopoletin (7), apterin (8), 3‐methoxy‐4‐β‐d‐glucopyranosyloxypropiophenone, (praeroside; 9), tachioside (10) and coniferin (11), were isolated from roots of Heracleum dissectum Ledeb. Their structures were elucidated on the basis of physicochemical properties and the detailed interpretation of various spectroscopic data. All the isolated compounds were screened for anti‐inflammatory activity in vitro. As the results, compound 1 and 8 showed significantly inhibitory activity on nitric oxide production in RAW264.7 cells.
Influence of Metal Doping on the Lewis Acid Catalyzed Production of Butadiene from Ethanol Studied by using Modulated Operando Diffuse Reflectance Infrared Fourier Transform Spectroscopy and Mass Spectrometry
Authors: Müller Philipp , Wang Shao‐Chun , Burt Samuel P. , Hermans Ive
Published: May 2017

As a result of the increasing gap between the supply and demand of butadiene, the catalytic coupling of ethanol has regained the attention of the scientific and industrial community as an “on‐purpose” production route to butadiene. The most promising systems are based on bifunctional catalysts that comprise metal sites that can dehydrogenate ethanol to acetaldehyde and Lewis acid sites that catalyze the aldol condensation between two aldehyde molecules and the Meerwein–Ponndorf–Verley reduction of the intermediate crotonaldehyde. Here, we investigate the role of Ag in an established Ag‐Zr‐BEA catalyst using modulated operando diffuse reflectance infrared Fourier transform spectroscopy and mass spectrometry experiments. We obtain insights into the complex reaction network that involves several consecutive and parallel reactions. Based on our investigations, we formulate suggestions for catalyst optimization.
A Composite of Pyrrole‐Doped Carbon Black Modified with Co3O4 for Efficient Electrochemical Oxygen Reduction Reaction
Authors: Liu Zhidong , Su Qingyun , Diao Peng , Li Fan
Published: May 2017

Low‐cost catalysts with high performance toward the oxygen reduction reaction (ORR) in energy conversion systems are intensively desired. Here, we report the preparation of a composite catalyst that is composed of pyrrole‐doped carbon black (py‐CB) and Co3O4 nanoparticles (NPs). The synergetic effect of Co3O4 and pyrrole on CB particles endows the obtained py‐CB/Co3O4 hybrid with pronounced catalytic activity toward the ORR. The onset potential of the hybrid is 0.88 V vs. RHE and the half‐wave potential is only 60 mV negative from that of the commercial Pt/C catalyst. The diffusion‐limit current density of this catalyst reaches 5.47 mA cm−2, which is very close to that of Pt/C. The electron‐transfer number of ORR on the py‐CB/Co3O4 is 3.9, indicating a desirable four‐electron reduction pathway. Moreover, the hybrid catalyst exhibits a much higher durability toward the ORR than the commercial Pt/C catalyst. The py‐CB/Co3O4 composite catalyst is highly competitive compared to other carbon‐based catalysts, owing to its high activity, excellent stability, and especially the use of inexpensive CB and the ease of preparation. This work may open a new avenue for the design and preparation of ORR catalysts based on cheap and commercially available CB.
Alpha‐ and Beta‐Diastereoisomers of Phenylcobalamin from Cobalt‐Arylation with Diphenyliodonium Chloride
Authors: Brenig Christopher , Ruetz Markus , Kieninger Christoph , Wurst Klaus , Kräutler Bernhard
Published: May 2017

Organometallic aryl‐cobalamins are B12‐derivatives featuring properties of potential ‘B12 antivitamins’. Herein, we describe a new method for the preparation of aryl‐cobalamins using versatile diaryliodonium salts as arylation agents. Formate or sodium borohydride reduction of aquocobalamin in presence of diphenyliodonium chloride furnished Coβ‐phenyl‐cobalamin PhCbl in a roughly 3:1 to 1:1 ratio with its coordination isomer αPhCbl, a first representative ‘base‐off’ Coα‐aryl‐cobalamin. The new structures were secured by detailed spectroscopic analysis, supplemented by an X‐ray crystal structure analysis of PhCbl. Both types of coordination isomers of the aryl‐cobalamins promise to be useful molecular tools in biomedical and biological studies.
Uniform Yolk–Shell MoS2@Carbon Microsphere Anodes for High‐Performance Lithium‐Ion Batteries
Authors: Pan Yunmei , Zhang Jiajia , Lu Hongbin
Published: May 2017

As an electrode material for lithium‐ion batteries (LIBs), MoS2 has attracted much attention because of its high capacity and low cost. However, the rational design of a novel electrode structure with a high capacity, fast charge/discharge rate, and long cycling lifetime remains a great challenge. Herein, a environmentally friendly etching strategy is reported for the construction of monodisperse, inner void‐controlled yolk–shell MoS2@carbon microspheres. The resulting anode reveals an initial discharge capacity up to 1813 mAh g−1, a high reversible capacity (1016 mAh g−1), excellent cycling stability (200 cycles), and superior rate performance. Such microspheres consist of nanosized MoS2 yolks (≈280 nm), porous carbon shells (≈25 nm) and well‐controlled internal voids in between, opening a new pathway for the optimization of the electrochemical properties of MoS2‐based anodes without sacrificing their capacity. In addition, this etching strategy offers a new method for the development of functional, hollow MoS2‐based composites.
α‐Quaternary Mannich Bases through Copper‐Catalyzed Amination‐Induced 1,2‐Rearrangement of Allylic Alcohols
Authors: Weng Wei‐Zhi , Sun Jian‐Guo , Li Ping , Zhang Bo
Published: May 2017

A novel copper‐catalyzed amination‐induced 1,2‐rearrangement reaction of allylic alcohols has been developed under simple and mild conditions. The commercially available N‐fluorobenzenesulfonimide (NFSI) is employed as an amination reagent. In this transformation, not only alkyl, but also aryl substituents can efficiently undergo 1,2‐carbon atom migration, thereby providing an efficient and powerful route to prepare a wide range of α‐quaternary Mannich bases. The reaction features a broad substrate scope, operational simplicity, and excellent practicality.
Adaptive parallel Delaunay triangulation construction with dynamic pruned binary tree model in Cloud
Authors: Lin Jiaxiang , Chen Riqing , Wu Liping , Shu Zhaogang , Yang Changcai
Published: May 2017

The paper illustrates a parallel and distributed scheme for computing a planar Delaunay triangulation using a divide‐and‐conquer strategy in Cloud environment, which combines the incremental insertion algorithm and the divide‐and‐conquer method. The proposed hybrid algorithm for Delaunay triangulation construction is easy to be parallelized due to the dynamic pruned characteristic of the binary tree model used. Moreover, the Cloud platform decreases the communication overhead and improves data locality by making use of a data partitioning and integrating scheme offered by the map‐reduce architecture. The implementation of the parallel and distributed version of the algorithm relied on a robust data structure called quad‐edge, which implies the geometric relationship among the edges and vertexes adjacent. More importantly, the data are serialized easily and transmitted efficiently between different Cloud nodes; the algorithm is executed conveniently on PC clusters. We tested the parallel version of the algorithm on GeoKSCloud, a geographical knowledge service Cloud developed by our research team. Experimental results show that the proposed hybrid algorithm is efficient and competitive; it can be easily migrated and deployed in distributed and parallel computing environment, such as grid and Cloud. The parallel implementation of the hybrid algorithm has a good speed‐up, while data communication is the crucial factor for the efficiency of the parallel version. Overall, the parallel version outperforms both the sequential divide‐and‐conquer algorithm and the sequential incremental insertion algorithm.
Regulatory Consequences of “Brexit” for the Development of Medicinal Products
Authors: Jackson EL , Feldschreiber P , Breckenridge A
Published: May 2017

The United Kingdom voted in a referendum in June 2016 to leave the European Union (EU) after 45 years of membership. Among the many political, social, and scientific consequences are those for the regulation of health care products. No longer will the efficacy, safety, and quality of medicines in the United Kingdom be subject to an EU regulatory framework. The European Medicines Agency (EMA), which is currently located in London, will move elsewhere in Europe. The pharmaceutical industry will reassess its commitment to the UK health scene.
Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia
Authors: Bijleveld YA , Mathôt RAA , van der Lee JH , Groenendaal F , Dijk PH , van Heijst A , Simons SHP , Dijkman KP , van Straaten HLM , Rijken M , Zonnenberg IA , Cools F , Zecic A , Nuytemans DHGM , van Kaam AH , de Haan TR ,   for the PharmaCool Study Group
Published: May 2017

The pharmacokinetics (PK) of amoxicillin in asphyxiated newborns undergoing moderate hypothermia were quantified using prospective data (N = 125). The population PK was described by a 2‐compartment model with a priori birthweight (BW) based allometric scaling. Significant correlations were observed between clearance (Cl) and postnatal age (PNA), gestational age (GA), body temperature (TEMP), and urine output (UO). For a typical patient with GA 40 weeks, BW 3,000 g, 2 days PNA (i.e., TEMP 33.5°C), and normal UO, Cl was 0.26 L/h (interindividual variability (IIV) 41.9%) and volume of distribution of the central compartment was 0.34 L/kg (IIV of 114.6%). For this patient, Cl increased to 0.41 L/h at PNA 5 days and TEMP 37.0°C. The respective contributions of both covariates were 23% and 27%. Based on Monte Carlo simulations we recommend 50 and 75 mg/kg/24h amoxicillin in three doses for patients with GA 36–37 and 38–42 weeks, respectively.