bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent ischemic stroke as a result of caseous calcifications of the mitral annulus under dual anti‐platelet therapy
Authors: Fukushima Naoya , Yoshizawa Hiroshi , Iijima Mutsumi , Nagashima Yoji , Yamasaki Kenji , Hagiwara Nobuhisa , Kitagawa Kazuo
Published: July 2017

We report on a patient with recurrent ischemic stroke as a result of caseous calcifications of the mitral annulus under dual anti‐platelet therapy. She underwent surgical removal of a calcified mass attached to the posterior mitral valve, and she had no recurrent stroke after surgery. Although mitral annular calcification is usually believed to be benign and at low risk of embolic complications, caseous calcifications of the mitral annulus might be at high risk of embolic stroke and refractory to medical treatment, such as anti‐thrombotic therapy. In patients with ischemic stroke of unknown etiology, thorough examination of uncommon cardiac sources is important. Although there is no established indication of surgical treatment for caseous calcifications of the mitral annulus, surgical removal would be considered when the patients experienced recurrent stroke under aggressive anti‐thrombotic therapy.
Acute complete bilateral ophthalmoplegia and ptosis without ataxia or areflexia associated with serum anti‐GQ1b antibody
Authors: Tsuzaki Koji , Tatsuno Kentaro , Inoue Manabu , Tachibana Naoko , Hamano Toshiaki
Published: July 2017

We report the case of a 65‐year‐old woman who presented with acute complete bilateral ophthalmoplegia and ptosis. Deep tendon reflexes were normal and there were no signs of ataxia. On laboratory examination, the patient had vitamin B1 deficiency; however, symptoms did not improve after fursultiamine administration. Thereafter, it was found that the patient was seropositive for anti‐ganglioside Q1b immunoglobulin G antibody, and she was diagnosed with acute ophthalmoplegia and ptosis associated with anti‐ganglioside Q1b immunoglobulin G antibody. The patient's symptoms improved gradually without further treatment over the next several months. Ataxia and areflexia were not observed during the clinical course.
Radiofrequency ablation of fast ventricular tachycardia causing an ICD storm in an infant with hypertrophic cardiomyopathy
Authors: Ergul Yakup , Ozyilmaz Isa , Bilici Meki , Ozturk Erkut , Haydin Sertaç , Guzeltas Alper
Published: July 2017

An implantable cardioverter defibrillator (ICD) storm involves very frequent arrhythmia episodes and ICD shocks, and it is associated with poor short‐term and long‐term prognosis. Radiofrequency catheter ablation can be used as an effective rescue treatment for patients with an ICD storm. To our knowledge, this is the first report of an infant with hypertrophic cardiomyopathy presenting with an ICD storm and undergoing successful radiofrequency catheter ablation salvage treatment for the fast left posterior fascicular ventricular tachycardia.
Commentary: Neighborhood Associations and Homeowner Associations: Do They Really Make a Difference in Your Community?
Authors: Turner Victor T.
Published: July 2017

Related Content: Craw (PAR September/October 2017)
Can Geospatial Data Improve House Price Indexes? A Hedonic Imputation Approach with Splines
Authors: Hill Robert J. , Scholz Michael
Published: July 2017

Determining how and when to use geospatial data (i.e. longitudes and latitudes for each house) is probably the most pressing open question in the house price index literature. This issue is particularly timely for national statistical institutes (NSIs) in the European Union, which are now required by Eurostat to produce official house price indexes. Our solution combines the hedonic imputation method with a flexible hedonic model that captures geospatial data using a non‐parametric spline surface. For Sydney, Australia, we find that the extra precision provided by geospatial data as compared with postcode dummies has only a marginal impact on the resulting hedonic price index. This is good news for resource‐stretched NSIs. At least for Sydney, postcodes seem to be sufficient to control for locational effects in a hedonic house price index.
A Penalized Inference Approach to Stochastic Block Modelling of Community Structure in the Italian Parliament
Authors: Signorelli Mirko , Wit Ernst C.
Published: July 2017

We analyse bill cosponsorship networks in the Italian Chamber of Deputies. In comparison with other parliaments, a distinguishing feature of the Chamber is the large number of political groups. Our analysis aims to infer the pattern of collaborations between these groups from data on bill cosponsorships. We propose an extension of stochastic block models for edge-valued graphs and derive measures of group productivity and of collaboration between political parties. As the model proposed encloses a large number of parameters, we pursue a penalized likelihood approach that enables us to infer a sparse reduced graph displaying collaborations between political parties.
Poor genetic differentiation but clear cytoform divergence among cryptic species in Simulium damnosum complex (Diptera: Simuliidae)
Authors: OFORKA LINDA C. , ADELEKE MONSURU A. , ANIKWE JOSEPH C. , HARDY NATE B. , MATHIAS DERRICK K. , MAKANJUOLA WINIFRED A. , FADAMIRO HENRY Y.
Published: July 2017

A complex cryptic species taxonomy has been developed for the flies that vector Onchocerca volvulus Leuckart in Africa. This taxonomy names cytoforms of Simulium damnosum Theobald s.l. based on chromosomal inversion polymorphisms. Researchers have linked variation in cytoforms to variation in geographical distributions and biological traits, but have failed to demonstrate that many of these cytoforms are differentiated genetically or morphologically. This may be explained by recent divergence and incomplete lineage sorting of ancestral polymorphisms. Alternatively, it may be the outcome of ongoing gene flow, with inversions maintaining sets of co‐adapted alleles and selection driving inversion frequency differences across habitats. Here, our goals were to test species delimitations in the S. damnosum complex, and determine if the poor differentiation between these species is better explained by the ancestral polymorphisms or gene‐flow hypotheses. Geometric morphometric analysis and more intensive genetic sampling of populations in Nigeria only reinforced the lack of clear divergence among S. damnosum complex cytoforms. By contrast, the first statistical estimates of evolutionary relationships based on chromosomal inversion polymorphism data revealed clear signs of divergence, which lends support to the ancestral polymorphisms hypothesis. But the latter analyses may be biased by non‐neutral evolution of inversion polymorphisms; more rigorous tests of cytoform‐based species hypothesis will require deeper sampling across populations and neutral genetic markers along with explicit modelling of genetic isolation and migration.
The Accusative‐Subject Generalization
Authors: Wood Jim
Published: July 2017

This article discusses the morphosyntax of accusative‐subject constructions in Icelandic, from the point of view of the “dependent case” analysis of accusative. The primary focus is on deriving the Accusative‐Subject Generalization (ASG), the generalization that accusative subjects are never related thematically to a morphologically intransitive verb. After it is demonstrated that the ASG holds, it is proposed that the ASG follows from the claim that there is no such thing as inherently case‐marked accusatives in Icelandic. The accusative‐subject constructions under scrutiny in fact involve a silent external argument that distributes like a clitic syntactically and is interpreted like a weather pronoun semantically. The account is explanatory insofar as it involves one stipulation—the presence of a silent clitic—from which the ASG and numerous other syntactic, semantic, and morphological properties of accusative‐subject constructions follow. The explanatory value of the account hinges on a grammatical architecture in which morphological idiosyncrasy and semantic idiosyncrasy are computed in distinct components of the grammar, and case marking—even structural case marking—is divorced from DP licensing.
Transfusion for sickle cell disease in pregnancy: a single‐centre survey
Authors: Sharif J. , Byrd L. , Stevenson K. , Raddats J. , Morsman E. , Ryan K.
Published: July 2017

Introduction

Sickle cell disease in pregnancy carries a high risk of maternal and fetal adverse outcomes. The use of prophylactic transfusions to reduce the risk of sickle complications is controversial. Current UK standards do not recommend the routine use of transfusion for sickle pregnancy.

We examined transfusion episodes during sickle pregnancies in a single centre over an 11‐year period.

Methods

We conducted a retrospective observational study of all pregnancies in patients with sickle cell disease who attended the joint obstetric/haematology clinic over an 11‐year period. All pregnancies were managed according to a local protocol, which did not recommend routine transfusion.

Results

A total of 38 pregnancies (HbSS 22, HbSC 13, Hb S/beta thalassaemia 3) were included, with a mean age at booking of 29 years. A total of 61% of pregnancies required on‐demand or emergency transfusion during the course of pregnancy or post‐partum. Women requiring a transfusion during pregnancy had a higher mean number of hospital admissions in the previous year (1·11 vs 0·15, P = 0·057), a significantly lower mean steady‐state haemoglobin (85·0 vs 99·6 g L−1, P = 0·003) and a significantly lower mean haemoglobin at the pregnancy booking visit. (86·1 vs 99·5 g L−1, P = 0·02).

Conclusion

In sickle pregnancies assigned to standard management in a single centre, a high proportion of women required on‐demand transfusion. Possible pre‐pregnancy factors predictive of a need for transfusion include lower baseline haemoglobin and number of hospital admissions in the previous 12 months.
Results of allergen‐specific immunotherapy in atopic dogs withMalasseziahypersensitivity: a retrospective study of 16 cases
Authors: Åberg Liselotte , Varjonen Katarina , Åhman Susanne
Published: July 2017

Background

Hypersensitivity reactions toMalasseziaspp have been shown to occur in dogs with atopic dermatitis (AD) and to cause exacerbation of clinical signs. Improvement of clinical signs following use of antifungal medication is seen with bothMalasseziaovergrowth orMalasseziahypersensitivity (MHS). Subcutaneous immunotherapy (SCIT) is considered a safe and effective treatment for management of canine AD. Adverse effects are considered rare.

Objectives

To report on the use ofSCITwithMalasseziaextracts in mono‐sensitized dogs.

Animals

Sixteen client owned dogs diagnosed withMHSand treated withSCIT.

Methods

A retrospective review of medical records of atopic dogs diagnosed withMHS, mono‐sensitized forMalasseziaallergens on intradermal test and treated withSCITfor more than 10 months. Efficacy was measured by decreasing use of anti‐inflammatory and antifungal medication by ≥50% and by decreasing pruritus by ≥50% as assessed by owners, using a pruritus score.

Results

Good response toSCITwas seen in nine of 16 cases (56%) with both a reduction in use of anti‐inflammatory and antifungal medication as well as a reduction in pruritus scores by ≥50%. No adverse effects were reported.

Conclusion

Allergen‐specific immunotherapy was a safe treatment for dogs withMalasseziahypersensitivity. The efficacy ofMalasseziaimmunotherapy corresponds well to the results of previous studies of immunotherapy with other environmental allergens.
The Role of Unconscious Awareness of Teachers within Teacher-child Relationship
Authors: Gölbaşı Elçin , Önder Alev
Published: July 2017

This article is a descriptive study which aims to investigate preschool teachers’ awareness of their own unconscious and the contribution of unconscious processes to educational activities. It presents a literary review on education as a meeting of the teacher and student at a certain point in time and space, not only at a knowledge level but also with their inner psychological processes. The classroom is an arena in which teachers question themselves via interaction, face their true self and unique characteristics. The educational environment can be purified with the search for the teacher’s awareness of the unconscious by eliminating ambitions, prejudices and negative psychological experiences. Only then does it transform into an environment of symbolism, higher level thinking and free thinking.
Metaphoric Perceptions of the Students of the Sports Sciences Faculty Regarding the Concept of Fair-play
Authors: Çağlayan Hakan Salim , Gül Özgür
Published: July 2017

The objective of this study is to reveal the perceptions of the students of the sports sciences faculty regarding the concept of “Fair-Play” by means of metaphors. 275 students [male(n=173), female(n=102)] studying at the Sports Sciences Faculty of Seljuk University in the fall semester of the 2016-2017 educational year took part in the study voluntarily.The data of the study were obtained by making the students complete the sentence of “Fair-Play is like………….. because………..” Every student was expected to create a metaphor regarding the concept of Fair-Play in that way. In this study, the research design of phenomenology was used and the analysis of the data was conducted by using the content analysis method.The perceptions of the students of the Sports Sciences Faculty for the concept of “Fair-Play” were scrutinized by way of the metaphor analysis method. In this scope, the process of analysis and construal of the metaphors developed by the students took place in five stages as (1) determination of the metaphors, (2) classification of the metaphors, (3) category development, (4) ensuring validity and reliability, and (5) transfer of the data to the SPSS package program for quantitative data analysis.According to the findings of the study, the students created totally 119 valid metaphors regarding the concept of “Fair-Play.”The metaphors were analyzed in terms of their common traits and brought together under seven conceptual categories. At the end of the study, it was determined that students have perceived Fair Play as the “Expression of Wisdom” by 27%; as the “Expression of Nature” by 25%; “as a Guide” by 19%; as the “Expression of Humanly Qualifications” by 13%; as the “Expression of Cleanness” by 8%; as the “Expression of Contradiction” by 5%; and as “Important Persons” by 3%.
Determination of the Perceptions of Primary School Students Regarding the Concept of Television
Authors: Güven Sevim
Published: July 2017

Main purpose of the study is to determine how television is perceived by primary school students by means of metaphors and statements in figures. Being designed as a qualitative study, this study was handled in phenomenology patter and axis. The study was conducted with participation of 57 students continuing their education in 3rd and 4th grade in May 2016. In formation of the study group, analogous sampling technique as one of the purposeful sampling methods was used. The study data were obtained by means of “document analysis” from qualitative research data collection methods. With the purpose of revealing mental images relating to television concepts, the primary school students participating into the study were given an A4 paper with the sentence “Television is like …, because …” to complete on one side, and they were requested to draw a picture about meaning of television concept for the students, and answer the question “What do you want to explain in this picture?” Class teachers provided help for this procedure. The data obtained at the end of the study were analyzed with descriptive analysis and semiological analysis. 57 primary school students participating into the study developed 45 different metaphors and drew 57 different pictures. It was observed as a result of the study that primary school students had more intense positive perceptions towards televisions in their metaphors, and they defined television as mostly a free time and amusement tool. In pictures drawn relating to television, it was detected that television is mostly in the centers of settlement and they mostly used iconic indication and symbol.
Light-induced picosecond rotational disordering of the inorganic sublattice in hybrid perovskites
Authors: Wu Xiaoxi , Tan Liang Z. , Shen Xiaozhe , Hu Te , Miyata Kiyoshi , Trinh M. Tuan , Li Renkai , Coffee Ryan , Liu Shi , Egger David A. , Makasyuk Igor , Zheng Qiang , Fry Alan , Robinson Joseph S. , Smith Matthew D. , Guzelturk Burak , Karunadasa Hemamala I. , Wang Xijie , Zhu Xiaoyang , Kronik Leeor , Rappe Andrew M. , Lindenberg Aaron M.
Published: July 2017

Absorption of light in hybrid perovskite solar cells leads to ultrafast large-amplitude deformations of the inorganic sublattice.
Generation of blue chrysanthemums by anthocyanin B-ring hydroxylation and glucosylation and its coloration mechanism
Authors: Noda Naonobu , Yoshioka Satoshi , Kishimoto Sanae , Nakayama Masayoshi , Douzono Mitsuru , Tanaka Yoshikazu , Aida Ryutaro
Published: July 2017

Coexpression of two anthocyanin modification genes elicits blue flower coloration through interaction with colorless flavonoids.
Community-level regulation of temporal trends in biodiversity
Authors: Gotelli Nicholas J. , Shimadzu Hideyasu , Dornelas Maria , McGill Brian , Moyes Faye , Magurran Anne E.
Published: July 2017

Temporal fluctuations in species richness are frequently regulated, exhibiting a tendency to return toward a central level.
A viral scaffolding protein triggers portal ring oligomerization and incorporation during procapsid assembly
Authors: Motwani Tina , Lokareddy Ravi K. , Dunbar Carmen A. , Cortines Juliana R. , Jarrold Martin F. , Cingolani Gino , Teschke Carolyn M.
Published: July 2017

A novel role for scaffolding protein in portal ring formation.
Residential relocation and change in social capital: A natural experiment from the 2011 Great East Japan Earthquake and Tsunami
Authors: Hikichi Hiroyuki , Sawada Yasuyuki , Tsuboya Toru , Aida Jun , Kondo Katsunori , Koyama Shihoko , Kawachi Ichiro
Published: July 2017

Group residential relocation of survivors helps to preserve social connections in the aftermath of a disaster.
A photonic platform for donor spin qubits in silicon
Authors: Morse Kevin J. , Abraham Rohan J. S. , DeAbreu Adam , Bowness Camille , Richards Timothy S. , Riemann Helge , Abrosimov Nikolay V. , Becker Peter , Pohl Hans-Joachim , Thewalt Michael L. W. , Simmons Stephanie
Published: July 2017

Chalcogen donors in silicon enable a scalable photonic cavity quantum electrodynamics solution for universal quantum computing.
Funders groan under growing review burden
Authors: de Vrieze Jop
Published: July 2017

Granting agencies want research on how to reduce pressure and maintain quality.
Atomic-layered Au clusters on α-MoC as catalysts for the low-temperature water-gas shift reaction
Authors: Yao Siyu , Zhang Xiao , Zhou Wu , Gao Rui , Xu Wenqian , Ye Yifan , Lin Lili , Wen Xiaodong , Liu Ping , Chen Bingbing , Crumlin Ethan , Guo Jinghua , Zuo Zhijun , Li Weizhen , Xie Jinglin , Lu Li , Kiely Christopher J. , Gu Lin , Shi Chuan , Rodriguez José A. , Ma Ding
Published: July 2017

Low-temperature CO removal

Carbon monoxide deactivates fuel cell catalysts, so it must be removed from H
2
generated from hydrocarbons on site. Yao
et al.
developed a catalyst composed of layered gold clusters on molybdenum carbide (MoC) nanoparticles to convert CO through its reaction with water into H
2
and CO
2
at temperatures as low as 150°C. Water was activated on MoC to form surface hydroxyl groups, which then reacted with CO adsorbed on the gold clusters.

Science
, this issue p.
389
Tough adhesives for diverse wet surfaces
Authors: Li J. , Celiz A. D. , Yang J. , Yang Q. , Wamala I. , Whyte W. , Seo B. R. , Vasilyev N. V. , Vlassak J. J. , Suo Z. , Mooney D. J.
Published: July 2017

Sticky even when wet

Tissue adhesives are used as an alternative to stitches or staples and can be
less damaging to the healthy tissues. But they can suffer from low
biocompatibility and poor matching of the mechanical properties with the
tissues. Li
et al.
combined an adhesive surface with a flexible
matrix to develop an adhesive that has the right level of stick but moves with
the surrounding tissues. The adhesive is effective in the presence of blood and
thus might work during wound repair.

Science
, this issue p.
378
Synthesis of FeH
5
: A layered structure with atomic hydrogen slabs
Authors: Pépin C. M. , Geneste G. , Dewaele A. , Mezouar M. , Loubeyre P.
Published: July 2017

Atomic hydrogen with an iron assist

Metal polyhydrides can be used at lower pressures to make material that might have atomic hydrogen bonding. Pépin
et al.
manage to synthesize an incredibly hydrogen-rich FeH
5
compound at 130 GPa pressure. The material consists of slabs of four thin planes of atomic hydrogen intercalated with layers of quasicubic FeH
3
units. These metal polyhydrides were stable at far more accessible pressures than pure hydrogen. This achievement provides an opportunity to investigate special electrical properties expected from atomic hydrogen bonding, such as superconductivity.

Science
, this issue p.
382
Spectral narrowing of x-ray pulses for precision spectroscopy with nuclear resonances
Authors: Heeg K. P. , Kaldun A. , Strohm C. , Reiser P. , Ott C. , Subramanian R. , Lentrodt D. , Haber J. , Wille H.-C. , Goerttler S. , Rüffer R. , Keitel C. H. , Röhlsberger R. , Pfeifer T. , Evers J.
Published: July 2017

Spectral narrowing of x-rays

Modern photon factories typically provide x-ray pulses that are orders of magnitude broader in frequency space than the corresponding atomic or nuclear resonances to be probed. For many spectroscopic applications, however, narrower x-ray light sources are desired. By using precise mechanical displacements of a reference absorber to simulate the effect of an x-ray control field, Heeg
et al.
show that they can spectrally narrow input x-ray pulses. The conversion of off-resonant photons into resonant ones results in increased pulse brilliance at the desired resonant frequency, thereby providing a sharp x-ray probe for precision spectroscopy.

Science
, this issue p.
375
Nanocrystalline copper films are never flat
Authors: Zhang Xiaopu , Han Jian , Plombon John J. , Sutton Adrian P. , Srolovitz David J. , Boland John J.
Published: July 2017

Flat-out failure of copper films

As integrated circuits shrink in size, so does their nanocrystalline metal wiring. Defects at the interfaces between crystallites (grain boundaries) can degrade wires' electrical and thermal conductivity, as well as their longevity. Using scanning tunneling microscopy, Zhang
et al.
showed that the surfaces of nanocrystalline copper films are not flat but rather have ridges and valleys created by the grains rotating out of plane, which then introduces grain boundary defects. Such defects might be avoided if films of different orientations could be grown.

Science
, this issue p.
397
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade
Authors: Le Dung T. , Durham Jennifer N. , Smith Kellie N. , Wang Hao , Bartlett Bjarne R. , Aulakh Laveet K. , Lu Steve , Kemberling Holly , Wilt Cara , Luber Brandon S. , Wong Fay , Azad Nilofer S. , Rucki Agnieszka A. , Laheru Dan , Donehower Ross , Zaheer Atif , Fisher George A. , Crocenzi Todd S. , Lee James J. , Greten Tim F. , Duffy Austin G. , Ciombor Kristen K. , Eyring Aleksandra D. , Lam Bao H. , Joe Andrew , Kang S. Peter , Holdhoff Matthias , Danilova Ludmila , Cope Leslie , Meyer Christian , Zhou Shibin , Goldberg Richard M. , Armstrong Deborah K. , Bever Katherine M. , Fader Amanda N. , Taube Janis , Housseau Franck , Spetzler David , Xiao Nianqing , Pardoll Drew M. , Papadopoulos Nickolas , Kinzler Kenneth W. , Eshleman James R. , Vogelstein Bert , Anders Robert A. , Diaz Luis A.
Published: July 2017

Predicting responses to immunotherapy

Colon cancers with loss-of-function mutations in the mismatch repair (MMR) pathway have favorable responses to PD-1 blockade immunotherapy. In a phase 2 clinical trial, Le
et al.
showed that treatment success is not just limited to colon cancer (see the Perspective by Goswami and Sharma). They found that a wide range of different cancer types with MMR deficiency also responded to PD-1 blockade. The trial included some patients with pancreatic cancer, which is one of the deadliest forms of cancer. The clinical trial is still ongoing, and around 20% of patients have so far achieved a complete response. MMR deficiency appears to be a biomarker for predicting successful treatment outcomes for several solid tumors and indicates a new therapeutic option for patients harboring MMR-deficient cancers.

Science
, this issue p.
409
; see also p.
358
Photolithography based on nanocrystals
Authors: Striccoli Marinella
Published: July 2017

Surface chemistry of all-inorganic nanomaterials enables three-dimensional patterning
Directing reconfigurable DNA nanoarrays
Authors: Yang Yang , Lin Chenxiang
Published: July 2017

Information flow, encoded in structure, can be relayed along a chain of engineered DNA
Nitrogen stewardship in the Anthropocene
Authors: Seitzinger Sybil P. , Phillips Leigh
Published: July 2017

How can nitrogen emissions be reduced and reused to reduce pressure on ecosystems?
Genetic biomarker for cancer immunotherapy
Authors: Goswami Sangeeta , Sharma Padmanee
Published: July 2017

A tumor-associated defect can identify patients to receive immune checkpoint therapy
Babesia microti: from Mice to Ticks to an Increasing Number of Highly Susceptible Humans
Authors: Westblade Lars F. , Simon Matthew S. , Mathison Blaine A. , Kirkman Laura A.
Published: July 2017

Babesia microti
, a zoonotic intraerythrocytic parasite, is the primary etiological agent of human babesiosis in the United States. Human infections range from subclinical illness to severe disease resulting in death, with symptoms being related to host immune status. Despite advances in our understanding and management of
B. microti
, the incidence of infection in the United States has increased. Therefore, research focused on eradicating disease and optimizing clinical management is essential. Here we review this remarkable organism, with emphasis on the clinical, diagnostic, and therapeutic aspects of human disease.
Determination of Disk Diffusion and MIC Quality Control Ranges for Nafithromycin (WCK 4873), a New Lactone-Ketolide
Authors: Hackel Meredith A. , Karlowsky James A. , Dressel Dana , Sahm Daniel F.
Published: July 2017

Disk diffusion and MIC quality control (QC) ranges were determined for nafithromycin, a new lactone-ketolide, following the completion of a nine-laboratory, Clinical and Laboratory Standards Institute (CLSI) document M23-defined tier 2 study. Five QC strains consistent with the spectrum of activity of nafithromycin were tested:
Staphylococcus aureus
ATCC 25923 (disk only),
S. aureus
ATCC 29213 (broth only),
Enterococcus faecalis
ATCC 29212 (broth only),
Streptococcus pneumoniae
ATCC 49619 (disk and broth), and
Haemophilus influenzae
ATCC 49247 (disk and broth). Nafithromycin disk diffusion QC ranges were determined to be 25 to 31 mm for
S. aureus
ATCC 25923, 25 to 31 mm for
S. pneumoniae
ATCC 49619, and 16 to 20 mm for
H. influenzae
ATCC 49247. Nafithromycin MIC QC ranges were determined to be 0.06 to 0.25 μg/ml for
S. aureus
ATCC 29213, 0.016 to 0.12 μg/ml for
E. faecalis
ATCC 29212, 0.008 to 0.03 μg/ml for
S. pneumoniae
ATCC 49619, and 2 to 8 μg/ml for
H. influenzae
ATCC 49247. All disk diffusion and MIC QC ranges established in this study were approved by the CLSI Subcommittee on Antimicrobial Susceptibility Testing at their June 2015 meeting and were initially reported in the 2017 M100S document. The QC ranges established in this study should be used for determining the
in vitro
activity of nafithromycin in phase 2 and phase 3 human clinical trials and subsequently for testing patient isolates and isolates in phase 4 surveillance studies.
Hepatitis C Virus Induces the Localization of Lipid Rafts to Autophagosomes for Its RNA Replication
Authors: Kim Ja Yeon , Wang Linya , Lee Jiyoung , Ou Jing-hsiung James
Published: July 2017

Autophagy plays important roles in maintaining cellular homeostasis. It uses double- or multiple-membrane vesicles termed autophagosomes to remove protein aggregates and damaged organelles from the cytoplasm for recycling. Hepatitis C virus (HCV) has been shown to induce autophagy to enhance its own replication. Here we describe a procedure that combines membrane flotation and affinity chromatography for the purification of autophagosomes from cells that harbor an HCV subgenomic RNA replicon. The purified autophagosomes had double- or multiple-membrane structures with a diameter ranging from 200 nm to 600 nm. The analysis of proteins associated with HCV-induced autophagosomes by proteomics led to the identification of HCV nonstructural proteins as well as proteins involved in membrane trafficking. Notably, caveolin-1, caveolin-2, and annexin A2, which are proteins associated with lipid rafts, were also identified. The association of lipid rafts with HCV-induced autophagosomes was confirmed by Western blotting, immunofluorescence microscopy, and immunoelectron microscopy. Their association with autophagosomes was also confirmed in HCV-infected cells. The association of lipid rafts with autophagosomes was specific to HCV, as it was not detected in autophagosomes induced by nutrient starvation. Further analysis indicated that the autophagosomes purified from HCV replicon cells could mediate HCV RNA replication in a lipid raft-dependent manner, as the depletion of cholesterol, a major component of lipid rafts, from autophagosomes abolished HCV RNA replication. Our studies thus demonstrated that HCV could specifically induce the association of lipid rafts with autophagosomes for its RNA replication.

IMPORTANCE
HCV can cause severe liver diseases, including cirrhosis and hepatocellular carcinoma, and is one of the most important human pathogens. Infection with HCV can lead to the reorganization of membrane structures in its host cells, including the induction of autophagosomes. In this study, we developed a procedure to purify HCV-induced autophagosomes and demonstrated that HCV could induce the localization of lipid rafts to autophagosomes to mediate its RNA replication. This finding provided important information for further understanding the life cycle of HCV and its interaction with the host cells.
Murine Gammaherpesvirus 68 Expressing Kaposi Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen (LANA) Reveals both Functional Conservation and Divergence in LANA Homologs
Authors: Gupta Arundhati , Oldenburg Darby G. , Salinas Eduardo , White Douglas W. , Forrest J. Craig
Published: July 2017

Latency-associated nuclear antigen (LANA) is a multifunctional protein encoded by members of the
Rhadinovirus
genus of gammaherpesviruses. Studies using murine gammaherpesvirus 68 (MHV68) demonstrated that LANA is important for acute replication, latency establishment, and reactivation
in vivo
. Despite structural similarities in their DNA-binding domains (DBDs), LANA homologs from Kaposi sarcoma-associated herpesvirus (KSHV) and MHV68 exhibit considerable sequence divergence. We sought to determine if KSHV and MHV68 LANA homologs are functionally interchangeable. We generated an MHV68 virus that encodes KSHV LANA (kLANA) in place of MHV68 LANA (mLANA) and evaluated the virus's capacity to replicate, establish and maintain latency, and reactivate. kLANA knock-in (KLKI) MHV68 was replication competent
in vitro
and
in vivo
but exhibited slower growth kinetics and lower titers than wild-type (WT) MHV68. Following inoculation of mice, KLKI MHV68 established and maintained latency in splenocytes and peritoneal cells but did not reactivate efficiently
ex vivo
. kLANA repressed the MHV68 promoter for
ORF50
, the gene that encodes the major lytic transactivator protein RTA, while mLANA did not, suggesting a likely mechanism for the KLKI MHV68 phenotypes. Bypassing this repression by providing MHV68 RTA in
trans
rescued KLKI MHV68 replication in tissue culture and enabled detection of KLKI MHV68 reactivation
ex vivo
. These data demonstrate that kLANA and mLANA are functionally interchangeable for establishment and maintenance of latency and suggest that repression of lytic replication by kLANA, as previously shown with KSHV, is a kLANA-specific function that is transferable to MHV68.

IMPORTANCE
Kaposi sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68) are members of the
Rhadinovirus
genus of gammaherpesviruses. These viruses establish lifelong infections that place their respective human and murine hosts at risk for cancer. Latency-associated nuclear antigen (LANA) is a conserved
Rhadinovirus
protein that is necessary for long-term chronic infection by these viruses. To better understand the conserved functions performed by LANA homologs, we generated a recombinant MHV68 virus that encodes the KSHV LANA protein in place of the MHV68 LANA homolog. We determined that the KSHV LANA protein is capable of supporting MHV68 latency in a mouse model of chronic infection but also functions to repress viral replication. This work describes an
in vivo
model system for defining evolutionarily conserved and divergent functions of LANA homologs in
Rhadinovirus
infection and disease.
Insufficient Innate Immunity Contributes to the Susceptibility of the Castaneous Mouse to Orthopoxvirus Infection
Authors: Earl Patricia L. , Americo Jeffrey L. , Moss Bernard
Published: July 2017

The castaneous (CAST) mouse, a wild-derived inbred strain, is highly susceptible to orthopoxvirus infection by intranasal and systemic routes. The 50% lethal intraperitoneal dose of vaccinia virus (VACV) was 3 PFU for CAST mice, whereas BALB/c mice survived 106PFU. At all times and in all organs analyzed, virus titers were higher in CAST than in BALB/c mice. In individual CAST mice, luciferase-expressing VACV was seen to replicate rapidly leading to death, whereas virus levels increased for a few days and then declined in BALB/c mice. Increases in gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) were delayed and low in CAST mice compared to BALB/c mice following VACV infection or poly(I-C) inoculation, consistent with differences in innate immune responses. In addition, naive CAST mice had considerably lower numbers of NK and T cells than BALB/c mice. The percentage of IFN-γ-producing CD4+and CD8+T cells increased following infection of CAST mice only after considerable virus spread, and the absolute cell numbers remained low. Administration of exogenous IFN-γ or -α to CAST mice before or during the first days of infection suppressed virus replication and prolonged survival, allowing the mice to make adaptive CD4+and CD8+T cell responses that were necessary to clear the virus after cessation of interferon treatment. Thus, insufficient innate cytokine and cellular immune responses contribute to the unique susceptibility of CAST mice to VACV, whereas the adaptive immune response can be protective only if virus replication is suppressed during the first several days of infection.

IMPORTANCEMost inbred mouse strains are relatively resistant to orthopoxviruses. The castaneous (CAST) mouse is a notable exception, exhibiting extreme vulnerability to monkeypox virus, cowpox virus, and vaccinia virus and thus providing a unique model for studying pathogenicity, immunity, vaccines, and antiviral drugs. To fully utilize the CAST mouse for such purposes, it is necessary to understand the basis for virus susceptibility. We showed that naive CAST mice make low IFN-γ and TNF-α responses and have low levels of NK cells and CD4+and CD8+T cells compared to a resistant classical inbred mouse strain. Attenuating virus replication with one or more doses of exogenous IFN-α or -γ before or during the first few days of infection enabled the development of adaptive cellular immunity and clearance of virus. Further genetic studies may reveal the basis for the low innate immunity.
LpxK Is Essential for Growth of Acinetobacter baumannii ATCC 19606: Relationship to Toxic Accumulation of Lipid A Pathway Intermediates
Authors: Wei Jun-Rong , Richie Daryl L. , Mostafavi Mina , Metzger Louis E. , Rath Christopher M. , Sawyer William S. , Takeoka Kenneth T. , Dean Charles R.
Published: July 2017

Acinetobacter baumannii
is a Gram-negative pathogen for which new therapies are needed. The lipid A biosynthetic pathway has several potential enzyme targets for the development of anti-Gram-negative agents (e.g., LpxC). However,
A. baumannii
ATCC 19606 can grow in the absence of LpxC and, correspondingly, of lipid A. In contrast, we show that cellular depletion of LpxK, a kinase occurring later in the pathway, inhibits growth. Growth inhibition results from toxic accumulation of lipid A pathway intermediates, since chemical inhibition of LpxC or fatty acid biosynthesis rescues cell growth upon loss of LpxK. Overall, this suggests that targets such as LpxK can be essential for growth even in those Gram-negative bacteria that do not require lipid A biosynthesis
per se
. This strain provides an elegant tool to derive a better understanding of the steps in a pathway that is the focus of intense interest for the development of novel antibacterials.
Phenotypic Differences between Asian and African Lineage Zika Viruses in Human Neural Progenitor Cells
Authors: Anfasa Fatih , Siegers Jurre Y. , van der Kroeg Mark , Mumtaz Noreen , Stalin Raj V. , de Vrij Femke M. S. , Widagdo W. , Gabriel Gülsah , Salinas Sara , Simonin Yannick , Reusken Chantal , Kushner Steven A. , Koopmans Marion P. G. , Haagmans Bart , Martina Byron E. E. , van Riel Debby
Published: July 2017

The mechanism by which ZIKV causes a range of neurological complications, especially congenital microcephaly, is not well understood. The fact that congenital microcephaly is associated with Asian lineage ZIKV strains raises the question of why this was not discovered earlier. One possible explanation is that Asian and African ZIKV strains differ in their abilities to infect cells of the CNS and to cause neurodevelopmental problems. Here, we show that Asian ZIKV strains infect and induce cell death in human neural progenitor cells—which are important target cells in the development of congenital microcephaly—less efficiently than African ZIKV strains. These features of Asian ZIKV strains likely contribute to their ability to cause chronic infections, often observed in congenital microcephaly cases. It is therefore likely that phenotypic differences between ZIKV strains could be, at least in part, responsible for the ability of Asian ZIKV strains to cause congenital microcephaly.
Identification of Rab18 as an Essential Host Factor for BK Polyomavirus Infection Using a Whole-Genome RNA Interference Screen
Authors: Zhao Linbo , Imperiale Michael J.
Published: July 2017

Polyomaviruses bind to a group of specific gangliosides on the plasma membrane of the cell prior to being endocytosed. They then follow a retrograde trafficking pathway to reach the endoplasmic reticulum (ER). The viruses begin to disassemble in the ER and then exit the ER and move to the nucleus. However, the details of intracellular trafficking between the endosome and the ER are largely unknown. By implementing a whole human genome small interfering RNA screen, we identified Rab18, syntaxin 18, and the NRZ complex as key components in endosome-ER trafficking of the human polyomavirus BKPyV. These results serve to further elucidate the route BKPyV takes from outside the cell to its site of replication in the nucleus.
A rare case of persistent nephropleural fistula following percutaneous nephrolithotomy
Authors: Bansal Devanshu , Nayak Brusabhanu , Singh Prabhjot , Srivastava Prashant
Published: July 2017

Nephropleural fistula following percutaneous nephrolithotomy (PCNL) is a very rare complication and there are only a few case reports available in the literature. We present a case of a 65-year-old male patient with a right staghorn renal calculus and a left upper ureteric calculus who developed a right nephropleural fistula following right-sided PCNL. The patient required intercostal tube drainage. The cause of the fistula was identified to be a superior calyceal infundibular obstruction due to tiny residual stone fragments and oedema, which was endoscopically dilated, and the fistula subsequently healed. Urinary diversion using chest drainage and percutaneous nephrostomy followed by infundibular dilation and removal of secondary stones allowed the successful closure of the nephropleural fistula in our case.
Long-term complications, reoperations and survival following cardioverter-defibrillator implant
Authors: Hawkins Nathaniel Mark , Grubisic Maja , Andrade Jason G , Huang Flora , Ding Lillian , Gao Min , Bashir Jamil
Published: July 2017

Objective

Implantable cardioverter-defibrillators (ICDs) reduce risk of death in select populations, but are also associated with harms. We aimed to characterise long-term complications and reoperation rate.

Methods

We assessed the rate, cumulative incidence and predictors of long-term reoperation and survival using a prospective, multicentre registry serving British Columbia in Canada, a universal single payer healthcare system with 4.5 million residents. 3410 patients (mean 63.3 years, 81.7% male) with new primary (n=1854) or secondary prevention (n=1556) ICD implant from 2003 to 2012 were followed for a median of 34 months (single chamber n=1069, dual chamber n=1905, biventricular n=436). Independent predictors of adverse outcomes were defined using Cox regression models.

Results

The overall reoperation rate was 12.0% per patient-year, and less for single vs dual vs biventricular ICDs (9.1% vs 12.5% vs 17.8% per patient-year, respectively). The Kaplan-Meier complication estimates (excluding generator end of life) at 1, 3 and 5 years were respectively: single chamber 10.2%, 16.2% and 21.6%; dual 11.7%, 19.1% and 27.4% and biventricular 15.9%, 22.2% and 24.7%. Cardiac resynchronisation therapy had the highest rate of early lead complications, but lower long-term need for upgrade. Device complexity, age and atrial fibrillation were key determinants of complications. Overall mortality at 1, 3 and 5 years was 5.4%, 17.4% and 32.7%, respectively. In younger patients, observed 5-year survival approached the expected survival in the general population (relative survival ratio=0.96 (0.90–0.98)). With increasing age, observed survival steadily declined relative to expected.

Conclusions

In a prospective registry capturing all procedures, complication and reoperation rates following de novo ICD implantation were high. Shared decision making must carefully consider these factors.
Evaluation of grading systems in stage I lung adenocarcinomas: a retrospective cohort study
Authors: Zombori Tamás , Furák József , Nyári Tibor , Cserni Gábor , Tiszlavicz László
Published: July 2017

Aims

There is no internationally accepted grading system for lung adenocarcinoma despite the new WHO classification. The architectural grade, the Kadota grade and the Sica score were evaluated and compared with overall (OS) and disease-free survival (DFS).

Methods

Comprehensive histological subtyping was used in a series of resected stage I lung adenocarcinoma to identify subtypes of adenocarcinomas, the architectural grade, the Kadota grade, the Sica grade, the mitotic count, nuclear atypia, the presence of lymphovascular, vascular and airway propagation, necrosis, and micropapillary or solid growth pattern in any percentage. Statistical models fitted included Kaplan-Meier estimates and Cox proportional hazard regression models.

Results

261 stage I adenocarcinomas were included. The 5-year survivals of different subtypes were as follows: lepidic (n=40, OS: 92.5%; DFS 91.6%), acinar (n=54, OS: 81.8%; DFS: 68.6%), papillary (n=49, OS: 73.6%; DFS: 61.0%), solid (n=95, OS: 64.7%; DFS: 57.8%) and micropapillary (n=23, OS: 34.8%; DFS: 33.5%). Concerning the architectural grade, there were significant differences between OS and DFS of low and intermediate (pOS=0.005, pDFS<0.001), low and high (pOS<0.001, pDFS<0.001) and intermediate and high grades (pOS=0.002, pDFS<0.001). Low-grade and intermediate grade tumours did not differ in survival according to Kadota grade and Sica grade. In the multivariable model, architectural grade was found to be an independent prognostic marker. In another model, architectural pattern proved to be superior to architectural grade.

Conclusions

Of the three grading systems compared, the architectural grade makes the best distinction between the outcome of low-grade, intermediate-grade and high-grade stage I adenocarcinomas.
The Risk of Postoperative Hemorrhage and Efficacy of Heparin for Preventing Deep Vein Thrombosis and Pulmonary Embolism in Adult Patients Undergoing Neurosurgery: A Systematic Review and Meta-Analysis
Authors: Wang Xuan , Zhou Ying-Chun , Zhu Wen-De , Sun Yun , Fu Peng , Lei De-Qiang , Zhao Hong-Yang
Published: July 2017

The aim of this meta-analysis was to examine the risk of postoperative bleeding and efficacy of heparin for preventing deep vein thrombosis (DVT) and pulmonary embolism (PE) in adult patients undergoing neurosurgery. MEDLINE, Cochrane, and EMBASE databases were searched until October 31, 2016, for randomized controlled trials (RCTs) and non-randomized comparative studies that assessed the rates of postoperative hemorrhage, DVT, PE, and mortality in adult patients undergoing neurosurgery. Nine eligible studies (five RCTs, four retrospective studies) including 874 patients treated with either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) and 1033 patients in control group (placebo with or without compression device) were analyzed. The overall analysis revealed that there was an increase in the risk of postoperative hemorrhage in patients who received heparin (pooled OR 1.66, 95% CI 1.01 to 2.72, p=0.046) compared with no treatment group. The risk of postoperative hemorrhage was more significant if only RCTs were included in analysis. Heparin prophylaxis was associated with a decrease in the risk of DVT (pooled OR 0.48, 95% CI 0.36 to 0.65, p<0.001) and PE (pooled OR 0.25, 95% CI 0.09 to 0.73, p=0.011) but it did not affect the rate of mortality. In conclusion, heparin increased the rate of postoperative bleeding, decreased the risk of DVT, PE and venous thromboembolic event (VTE) but it did not affect the mortality of patients undergoing neurosurgery. For the heparin prophylaxis, the trade-off between the risk of postoperative bleeding and benefit of prophylaxis against VTEs requires further investigation.
Nesting stage and distance to refuge influence terrestrial nesting behavior of Painted Turtles (Chrysemys picta)
Authors: Delaney David M. , Janzen Fredric J. , Warner Daniel A.
Published: July 2017

Theory predicts prey should flee to safety when the fitness benefits of flight meet or exceed the costs. Empirical work has shown the importance of predation risk (e.g., predator behavior, distance to refuge) to prey flight behavior. However, less is known about the influence of flight costs. We monitored nesting Painted Turtles (Chrysemys picta (Schneider, 1783)) to examine their response to a human observer (potential predator) depending on the distance between a turtle and an observer, distance between a turtle and water (i.e., refuge), and nesting stage at the time of the encounter (i.e., searching for a nest site vs. constructing a nest). We found no evidence that the distance to an observer influenced flight decisions. However, turtles were less likely to flee as the distance to water increased, and turtles already constructing nests were more likely to continue nesting than those still searching for nest sites. Turtles that traveled farther from water and that were constructing nests may have continued nesting because they had invested considerable energy and were close to completing oviposition. Thus, the fitness benefits of being closer to successful oviposition may outweigh the costs of increased vulnerability to predators during this important and vulnerable period of reproduction.