bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin K Antagonists Versus Novel Oral Anticoagulants for Elective Electrical Cardioversion of Atrial Fibrillation
Authors: Ţînţ Diana , Petriş Antoniu O. , Pop Ioana , Melnic Rimma , Ignat Andreea-Mihaela , Rogozea Liliana M.
Published: June 2017

Background:

The management strategy for patients with atrial fibrillation (AF) is often very complex, electrical cardioversion (EC) being often used to restore sinus rhythm in those patients. The increased risk of thromboembolic complications was lowered using anticoagulation therapy. Usually, the anticoagulation was achieved using vitamin K antagonists (VKAs), but over the last years we witnessed a wide implementation of the novel oral anticoagulants (NOACs).

Study Question:

Study question was to compare the efficacy of NOACs versus VKAs in patients undergoing elective EC for persistent AF, by assessing the presence of left atrial spontaneous contrast and left atrial thrombi (LACS), as well as the occurrence of the thromboembolic events in the first month after the procedure.

Study Design:

A prospective study, including patients with persistent AF enrolled between January 1, 2015 and December 31, 2016, was conducted in 2 tertiary cardiology clinics. In all these patients, a management strategy based on EC was considered for the treatment of the disease. All patients received anticoagulant therapy for at least 3 weeks before cardioversion. The data of 103 patients were analyzed.

Results:

The patients were divided into 2 groups: group A—VKAs treated—included 45 patients (43.68%), mean age 65.3 ± 12.47, 36% women; group B—NOACs treated—included 58 patients (56.31%), mean age 66.4 ± 9.79, 46% women. There was a trend toward higher incidence of left atrial thrombi in group B (16.28%) versus group A (7.69%), but the difference was not statistically significant (P = 0.5). The incidence of LACS was 40% in group A and 29% in group B, (P = 0.54).

Conclusion:

There are no statistically significant differences between the transesophageal echocardiography characteristics of left atrium and left atrial appendage examinations in the patients who received anticoagulation with VKAs as compared to patients who received anticoagulation with NOACs.
Neural Responses to Heartbeats of Physically Trained and Sedentary Young Adults
Authors: Perakakis Pandelis , Luque Casado Antonio , Ciria Luis , Ivanov Plamen , Sanabria Daniel
Published: June 2017

Regular physical exercise has a positive impact on brain function and cognitive performance. However, it is not yet clear whether the physiological and behavioral benefits associated to physical exercise are caused exclusively by changes in cardiovascular fitness. Here, we explore the relation between regular physical exercise and transient electroencephalographic responses to afferent cardiac signals. We find differences in the neural processing of heartbeats between individuals who exercise regularly and their sedentary counterparts. These differences, localised at two distinct spatio-temporal clusters, occur before the presentation of a target stimulus and correlate with behavioral performance only in the high-fit group. We hypothesise that the different neural processing of afferent cardiac activity by physically trained individuals reflects enhanced interoceptive sensitivity, which contributes to improved sustained attention. Our results are in line with recent research highlighting the role of neural monitoring of visceral signals in perceptual processing and even the generation of the sense of self.
Genetic-metabolic coupling for targeted metabolic engineering
Authors: Cardinale Stefano , Gonzalo Tueros Felipe , Otto Alexander Sommer Morten
Published: June 2017

To produce chemicals, microbes typically employ potent biosynthetic enzymes that interact with native metabolism to affect cell fitness as well as chemical production. However, production optimization largely relies on data collected from wild type strains in the absence of metabolic perturbations, thus limiting their relevance to specific process scenarios. Here, we address this issue by coupling cell fitness to the production of thiamine diphosphate inEscherichia coliusing a synthetic RNA biosensor.

We apply this system to interrogate a library of transposon mutants to elucidate the native gene network influencing both cell fitness and thiamine production. Specifically, we identify uncharacterized effectors of the OxyR-SoxR stress response that limit thiamine biosynthesis via alternative regulation of iron storage and Fe-S-cluster inclusion in enzymes.

Our study represents a new generalizable approach for the reliable high-throughput identification of genetic targets of both known and unknown function that are directly relevant to a specific biosynthetic process.
CRISPRi is not strand-specific and redefines the transcriptional landscape
Authors: Howe Françoise S. , Russell Andrew , El-Sagheer Afaf , Nair Anitha , Brown Tom , Mellor Jane
Published: June 2017

CRISPRi, an adapted CRISPR-Cas9 system, is proposed to act as a strand-specific roadblock to repress transcription in eukaryotic cells using guide RNAs (sgRNAs) to target catalytically inactive Cas9 (dCas9) and offers an alternative to genetic interventions for studying pervasive antisense transcription. Here we successfully use click chemistry to construct DNA templates for sgRNA expression and show, rather than acting simply as a roadblock, binding of sgRNA/dCas9 creates an environment that is permissive for transcription initiation and termination, thus generating novel sense and antisense transcripts. AtHMS2inSaccharomyces cerevisiae, sgRNA/dCas9 targeting to the non-template strand results in antisense transcription termination, premature termination of a proportion of sense transcripts and initiation of a novel antisense transcript downstream of the sgRNA/dCas9 binding site. This redefinition of the transcriptional landscape by CRISPRi demonstrates that it is not strand-specific and highlights the controls and locus understanding required to properly interpret results from CRISPRi interventions.
Do Avoidable Hospitalization Rates among Older Adults Differ by Geographic Access to Primary Care Physicians?
Authors: Daly Michael R. , Mellor Jennifer M. , Millones Marco
Published: June 2017

Objective

To investigate the association between older adults’ potentially avoidable hospitalization rates and both a geographic measure of primary care physician (PCP) access and a standard bounded‐area measure of PCP access.

Data Sources

State physician licensure data from the Virginia Board of Medicine. Patient‐level hospital discharge data from Virginia Health Information. Area‐level data from the American Community Survey and the Area Health Resources Files. Virginia Information Technologies Agency road network data. US Census Bureau TIGER/Line boundary files.

Study Design

We use enhanced two‐step floating catchment area methods to calculate geographic PCP accessibility for each ZIP Code Tabulation Area in Virginia. We use spatial regression techniques to model potentially avoidable hospitalization rates.

Data Collection/Extraction

Geographic accessibility was calculated using ArcGIS. Physician locations were geocoded using TAMU GeoServices and ArcGIS.

Principal Findings

Increased geographic access to PCPs is associated with lower rates of potentially avoidable hospitalization among older adults. This association is robust, allowing for spatial spillovers in spatial lag models.

Conclusions

Compared to bounded‐area density measures, unbounded geographic accessibility measures provide more robust evidence that avoidable hospitalization rates are lower in areas with more PCPs per person. Results from our spatial lag models reveal the presence of positive spatial spillovers.
Efficacy of Substance Removal by Immunoadsorption With a Selective Plasma Separator
Authors: Hanafusa Norio , Yamamoto Hiroko , Tamachi Masaki , Torato Toshihiro , Sakurai Satoko , Tsuchiya Ken , Nitta Kosaku , Nangaku Masaomi
Published: June 2017

Immunoadsorption with a tryptophan‐conjugated column has a limited capacity and reduces fibrinogen. We speculated that immunoadsorption with a selective plasma separator has higher efficiency in removing immunoglobulins than ordinary immunoadsorption without affecting coagulation factors. This study investigated the efficacy of immunoadsorption with a selective plasma separator in vitro. The sieving coefficients, the pool concentration, and the adsorbed amount were investigated serially with up to 5 L of processed plasma. The sieving coefficients of the selective plasma separator were 0.8, 0.5, and 0.1 for albumin, immunoglobulin G (IgG), and factor 13, respectively. The trend of concentrations for the ordinary plasma separator in the pool reached its nadir at 1.5 L and 3.5 L of plasma processed for IgG, IgG1, or IgG2, and IgG3, respectively. However, the volume was doubled for the selective plasma separator. The trends of fibrinogen and factor 13 concentrations differed significantly between two plasma separators. The trends of the absorbed amount were mirror images of the concentration in the pool. Comparison of the peak amount absorbed indicated that the amounts were almost identical between the two separators for IgG, IgG1, and IgG2. On the other hand, the peak amounts were less for albumin, fibrinogen, and IgG3 with the selective plasma separator than with the ordinary separator. Although further investigations about bradykinin are required, immunoadsorption with the selective plasma separator supports the administration of more frequent and intensive treatments to remove IgG1 or IgG2 without affecting coagulation factors.
The impact of serum potassium‐influencing antihypertensive drugs on the risk of out‐of‐hospital cardiac arrest: A case–control study
Authors: Alharbi Fawaz F. , Souverein Patrick C. , de Groot Mark C. H. , Blom Marieke T. , de Boer Anthonius , Klungel Olaf H. , Tan Hanno L.
Published: June 2017

Aims

Sudden cardiac arrest (SCA) is a complex multifactorial event and most commonly caused by ventricular tachycardia/ fibrillation (VT/ VF). Some antihypertensive drugs could induce hypokalaemia or hyperkalaemia, which may increase susceptibility to VT/VF and SCA.

Objective

To assess the association between different classes of antihypertensive drugs classified according to their potential impact on serum potassium levels and the occurrence of out‐of‐hospital cardiac arrest (OHCA) based on VT/VF.

Methods

A case–control study was performed among current users of antihypertensive drugs. Cases were OHCA victims with electrocardiogram documented VT/VF drawn from the AmsteRdam REsuscitation STudies (ARREST) registry, and controls were non‐OHCA individuals from the PHARMO database. Antihypertensive drugs were classified into: (i) antihypertensives with neutral effect on serum potassium levels; (ii) hypokalaemia‐inducing antihypertensives; (iii) hyperkalaemia‐inducing antihypertensives; (iv) combination of antihypertensives with hypo‐ and hyperkalaemic effects.

Results

We included 1345 cases and 4145 controls. The risk of OHCA was significantly increased among users of hypokalaemia‐inducing antihypertensives [adjusted odds ratio (OR) 1.39; 95% confidence interval (CI) 1.10–1.76] and among users of a combination of antihypertensives with hypo‐ and hyperkalaemic effects (adjusted OR 1.42; 95%CI 1.17–1.72) vs. users of antihypertensives with neutral effect. There was no difference in OHCA risk between users of hyperkalaemia‐inducing antihypertensives vs. users of antihypertensive drugs with neutral effect (adjusted OR 1.15; 95%CI 0.95–1.40).

Conclusion

The risk of OHCA is significantly increased in patients who were current users of hypokalaemia‐inducing antihypertensives and patients using a combination of antihypertensives with hypo‐ and hyperkalaemic effects.
Next generation phenotyping in Emanuel and Pallister‐Killian syndrome using computer‐aided facial dysmorphology analysis of 2D photos
Authors: Liehr T. , Acquarola N. , Pyle K. , St‐Pierre S. , Rinholm M. , Bar O. , Wilhelm K. , Schreyer I.
Published: June 2017

High throughput approaches are continuously progressing and have become a major part of clinical diagnostics. Still, the critical process of detailed phenotyping and gathering clinical information has not changed much in the last decades. Forms of next generation phenotyping (NGP) are needed to increase further the value of any kind of genetic approaches, including timely consideration of (molecular) cytogenetics during the diagnostic quest. As NGP we used in this study the facial dysmorphology novel analysis (FDNA) technology to automatically identify facial phenotypes associated with Emanuel (ES) and Pallister‐Killian Syndrome (PKS) from 2D facial photos. The comparison between ES or PKS and normal individuals expressed a full separation between the cohorts. Our results show that NPG is able to help in the clinic, and could reduce the time patients spend in diagnostic odyssey. It also helps to differentiate ES or PKS from each other and other patients with small supernumerary marker chromosomes, especially in countries with no access to more sophisticated genetic approaches apart from banding cytogenetics. Inclusion of more facial pictures of patient with sSMC, like isochromosome‐18p‐, cat‐eye‐syndrome or others may contribute to higher detection rates in future.
Effects of off‐highway vehicles on sandy habitat critical to survival of a rare beetle
Authors: Knisley Charles B. , Gowan Charles , Fenster Michael S.
Published: June 2017

Recreational activity, including use of off‐highway vehicles, threatens a variety of rare taxa that depend on undisturbed marine beaches, freshwater shorelines, aeolian dunes and other sandy habitats.

The endemic Coral Pink Sand Dunes (CPSD) tiger beetle (Cicindela albissima Rumpp) occupies a 300 × 1500 m area within a larger dune field in southwestern Utah.

Our objectives were to determine the habitat required by larvae, explain why habitat is so restricted, and to quantify how off‐highway vehicles (OHVs) affected habitat.

Macrohabitat characteristics (subsurface moisture, sediment grain size, compaction, vegetation cover) were not different in areas containing high beetle densities compared to those with low.

Within the core area containing most beetles, larvae were found primarily in microhabitats with cohesive sand close to the surface.

Compaction and moisture provide the cohesive sand required for larvae to maintain burrows during development. Compacted sand, soil moisture and vegetation supporting larval prey were largely absent in heavy OHV‐use areas.

Larvae were less abundant within OHV tracks compared to non‐track areas. Apparent survival of larvae experimentally translocated to OHV tracks was lower than that of larvae translocated to non‐OHV areas.

Our results show that beetles are restricted to an area where cohesive sand occurs near the surface, interspersed with sufficient vegetation to produce prey. These conditions are localised to an area where dunes migrate at a rate sustaining these conditions.

Restricting OHV use from all areas where natural processes create cohesive sand covered with adequate vegetation will minimise extinction probability for the beetle.
Pain associated with pressure injury: A qualitative study of community‐based, home‐dwelling individuals
Authors: Jackson Debra , Durrant Lisa , Bishop Emily , Walthall Helen , Betteridge Ria , Gardner Sarah , Coulton Wendy , Hutchinson Marie , Neville Stephen , Davidson Patricia M. , Usher Kim
Published: June 2017

Aims

The aim of this study was to provide deep insights into the pain associated with pressure injuries in home‐dwelling individuals using narrative accounts.

Background

Pressure injuries or pressure ulcers are burdensome and costly. Prevalence data, surveys and systematic reviews demonstrate that pain associated with pressure injury is widespread, but voices of home‐dwelling patients have remained largely unheard.

Design

Concurrent mixed methods case study of a UK community of approximately 50,000 adults.

Methods

Qualitative interviews, conducted in 2016, of 12 home‐dwelling adult participants with a current pressure injury (n = 10), or a recently healed pressure injury (n = 2).

Findings

Pain had an adverse impact on activities of daily living, mobility and sleep. Participants described days that were clouded in pain; a pain they felt was poorly understood and often out of control. Thematic content analysis revealed two major themes; these are: Poorly controlled pain: “I just want the pain to go away”; and, Uncertainty for the future: “it almost seems insurmountable.”

Conclusion

Findings of our study support the need to develop an appropriate assessment tool for pressure injury patients in the community to enable healthcare professionals and patients to recognize and manage pressure injury‐related pain effectively.
An epidemiological study of cataracts in wild and farmed lumpfish (Cyclopterus lumpus L.) and the relation to nutrition
Authors: Jonassen T , Hamadi M , Remø S C , Waagbø R
Published: June 2017

Twelve groups of farmed lumpfish and one of wild lumpfish were screened for cataract and sampled for fish muscle tissue, whole heart and both eye lenses to investigate possible relations between cataract and tissue free amino acid concentrations. Cataract prevalence ranged from 20% to 100%, with the highest average score of 7.3 (max 8) and incidences of severe cataract (>5) in all groups. Cataract could not be explained by suboptimal histidine concentrations in the feed. Neither muscle nor cardiac tissues had concentrations of free histidine compounds. The lumpfish lens contained N‐acetylhistidine (NAH), of which low concentrations were strongly related to cataract severity. However, no correlation between lens NAH and cataract severity was found in the present sample set. Wild lumpfish had higher levels compared to farmed lumpfish, suggesting that the farmed lumpfish may have been deficient in histidine or have a higher utilization of NAH due to osmotic problems. Thus, cataract in farmed lumpfish may be related to primary or secondary disturbed nutrient metabolism or malnutrition, shown by the high levels of specific amino acids in different tissues, which may cause osmotic imbalance and cataract development. This nutritional or environmental‐related welfare problem deserves further research.
Four new species of Talaromyces from clinical sources
Authors: Guevara‐Suarez Marcela , Sutton Deanna A. , Gené Josepa , García Dania , Wiederhold Nathan , Guarro Josep , Cano‐Lira José F.
Published: June 2017

The genus Talaromyces constitutes an important group of molds with species that are mainly found in soil, indoor environments and food products. Traditionally, it has been considered, together with Eupenicillium, the teleomorphic state of Penicillium. However, the taxonomy of these fungi has changed considerably, and Talaromyces currently includes sexually and asexually reproducing species. In a previous study of the occurrence of penicillium‐like fungi from clinical samples in the USA, we used the combined phylogeny of the internal transcribed spacer (ITS) region of the rDNA and β‐tubulin (BenA) gene to identify 31 isolates of Talaromyces, 85 of Penicillium and two of Rasamsonia. However, seven isolates of Talaromyces were assigned to the corresponding sections but not to any particular species. In this study, we have resolved the taxonomy of these isolates through a multilocus sequence analysis of the ITS, fragments of the BenA, calmodulin (CaM), and RNA polymerase II second largest subunit (RPB2) genes, and a detailed phenotypic study. As a result, four new species are described and illustrated, ie Talaromyces alveolaris, T. georgiensis, T. minnesotensis and T. rapidus.
Prednisolone for the first rhinovirus‐induced wheezing and 4‐year asthma risk: A randomized trial
Authors: Koistinen Annamari , Lukkarinen Minna , Turunen Riitta , Vuorinen Tytti , Vahlberg Tero , Camargo Carlos A. , Gern James , Ruuskanen Olli , Jartti Tuomas
Published: June 2017

Background

Previous findings show that corticosteroid treatment during the first acute wheezing episode may reduce recurrent wheezing in children with high rhinovirus genome load at 12‐month follow‐up. Longer‐term effects have not been investigated prospectively.

Methods

After PCR confirmation of rhinovirus from nasopharyngeal aspirate, 79 children with the first acute wheezing episode were randomized to receive orally prednisolone or placebo for 3 days. The initiation of asthma control medication before the age of 5 years was confirmed from medical record and/or from parental interview. The outcome was the time to initiation of regular asthma control medication. Interaction analysis examined rhinovirus genome load.

Results

Fifty‐nine (75%) children completed the follow‐up. Asthma control medication was initiated in 40 (68%) children at the median age of 20 months. Overall, prednisolone did not affect the time to initiation of asthma control medication when compared to placebo (P=.99). Rhinovirus load modified the effect of prednisolone regarding the time to initiation of asthma control medication (P‐value for interaction=.04). In children with high rhinovirus load (>7000 copies/mL; n=23), the risk for initiation of medication was lower in the prednisolone group compared to the placebo group (P=.05). In the placebo group, asthma medication was initiated to all children with high rhinovirus load (n=9) during the 14 months after the first wheezing episode.

Conclusions

Overall, prednisolone did not affect the time to initiation of asthma control medication when compared to placebo. However, prednisolone may be beneficial in first‐time wheezing children whose episode was severe and associated with high rhinovirus load. (ClinicalTrials.gov, NCT00731575).
Linear Unilateral Basaloid Follicular Hamartoma Following Blaschko's Lines: Two Case Reports and Review of the Literature
Authors: López Jiménez Esmeralda C. , Grau Cristina , Islas Norris Diana , Montenegro Dámaso Társila , Azón Antoni , Borrego Hernando Leopoldo
Published: June 2017

Basaloid follicular hamartoma (BFH) is a rare follicular malformation characterized by variable clinical presentations and identical histopathologic features. We present the cases of a 3‐month‐old boy and an 8‐year‐old boy with linear unilateral BFH. To the best of our knowledge, only 14 cases of linear unilateral BFH have been described in the English‐language literature.
Chlorogenic acid supplementation during in vitro maturation improves maturation, fertilization and developmental competence of porcine oocytes
Authors: Nguyen T‐V , Tanihara F , Do LTK , Sato Y , Taniguchi M , Takagi M , Van Nguyen T , Otoi T
Published: June 2017

Contents

Chlorogenic acid (CGA) is a quinic acid conjugate of caffeic acid, and a phytochemical found in many fruits and beverages that acts as an antioxidant. The present study investigated the effects of CGA supplementation during in vitro maturation (IVM), on in vitro development of porcine oocytes, to improve the porcine in vitro production (IVP) system. Oocytes were matured either without (control) or with CGA (10, 50, 100 and 200 μM). Subsequently, the matured oocytes were fertilized and cultured in vitro for 7 day. The rates of maturation, fertilization and blastocyst formation of oocytes matured with 50 μM CGA were significantly (p < .05) higher than those of the control oocytes. Hydrogen peroxide (H2O2) is one of the reactive oxygen species and induces DNA damage in porcine oocytes. When oocytes were matured with 1 mM H2O2 to assess the protective effect of CGA, 50 μM CGA supplementation improved the maturation rate and the proportion of DNA‐fragmented nuclei in oocytes compared with control oocytes matured without CGA. Moreover, when oocytes were matured with either 50 μM CGA (control) or caffeic acid (10, 50 and 100 μM), the rates of maturation, fertilization and the blastocyst formation of oocytes matured with 50 μM CGA were similar to those of oocytes matured with 10 and 50 μM caffeic acid. Our results suggest that CGA has comparable effects to caffeic acid, and IVM with 50 μM CGA is particularly beneficial to IVP of porcine embryos and protects oocytes from DNA damage induced by oxidative stress. Supplementation of CGA to the maturation medium has a potential to improve porcine IVP system.
Cryopreservation of Nili‐Ravi buffalo (Bubalus bubalis) semen in AndroMed® extender; in vitro and in vivo evaluation
Authors: Ansari MS , Rakha BA , Akhter S
Published: June 2017

Contents

The study was designed to evaluate AndroMed® for the freezability and fertility of Nili‐Ravi buffalo semen. Semen was collected from four adult Nili‐Ravi buffalo (Bubalus bubalis) bulls for 3 weeks (replicate). Semen ejaculates from each buffalo bull were divided into three aliquots. One aliquot was used for evaluation of motility, plasma membrane integrity, livability, viability, DNA integrity and normal apical ridge. Remaining two aliquots were diluted (37°C; 50 × 106 spermatozoa/ml) in tris‐citric egg yolk or AndroMed® extender and cryopreserved in 0.5 ml French straws. After thawing, per cent post‐thaw motility (47.9 ± 0.8, 49.2 ± 1.7), plasma membrane integrity (44.4 ± 1.2, 46.8 ± 1.8) and normal apical ridge (81.4 ± 0.3, 83.2 ± 0.3) were recorded similar (p > .05) in tris‐citric egg yolk and AndroMed® extender. Higher (p < .05) percentage of sperm livability (70.5 ± 1.4 and 64.4 ± 1.0), viability (67.5 ± 1.5 and 61.5 ± 0.6) and DNA integrity (97.0 ± 0.3 and 93.4 ± 0.21) were recorded in AndroMed® compared to tris‐citric egg yolk post‐thaw. Values for all the aforementioned spermatozoal quality parameters were observed lower (p < .05) in frozen‐thawed compared to fresh semen irrespective of the experimental extenders. Fertility rates of buffalo semen did not differ (p > .05) either cryopreserved in tris‐citric egg yolk or AndroMed® extender (45.5% vs. 49%). It is concluded that AndroMed® is capable in protecting the buffalo bull sperm during freeze‐thawing process and can be adopted safely for routine use replacing the tris‐citric egg yolk extender in artificial insemination programme.
Blood wastage management in a regional blood transfusion centre
Authors: Javadzadeh Shahshahani H. , Taghvai N.
Published: June 2017

Objectives

The aim of this study was to determine the rate of blood component wastage before and after interventions at Yazd Blood Transfusion Center.

Background

The growing need for blood components along with blood safety issues and rising costs constantly pressurise blood centres to improve their efficiency. Reducing the quantity of discarded blood at all stages of the supply chain can decrease the total costs.

Methods

Data on discarded blood components were extracted from the database of Yazd Blood Transfusion Center. Multiple interventions, including implementation of wastage management standard operating procedures and reduction of red blood cells (RBCs) inventory level, were implemented. Discard rates of blood components in the 3 years after intervention (2013–2015) were compared with the discard rates in the 3 years before interventions.

Results

The total wastage rate of blood components decreased by almost 60%. Discard rates of RBCs, platelets and plasma decreased from 9·7%, 18·5% and 5·4% to 2·9%, 10·5% and 2·3%, (P < 0·001) after intervention, respectively. The most prevalent reason for discarding units was expiration of RBCs and platelets. Plasma units were discarded mostly due to technical faults during processing. The cost saving of reduction in blood wastage was estimated to be 1,500,000 dollars.

Conclusion

Interventions had a significant impact on the reduction of blood wastage with respect to both cost and blood supply saving.
Can U.S. states and cities overcome Paris exit?
Authors: Cornwall Warren
Published: June 2017

Emissions will keep declining, but likely not enough for the United States to meet 2025 goal.
Observation of Anderson localization in disordered nanophotonic structures
Authors: Sheinfux Hanan Herzig , Lumer Yaakov , Ankonina Guy , Genack Azriel Z. , Bartal Guy , Segev Mordechai
Published: June 2017

Localizing light at the nanometer scale

Waves will propagate through a medium until scattering processes result in the excitation
gradually dying away. Introducing disorder can affect that propagation by increasing the
scattering, potentially reaching a point where transport is stopped. Typically, the
length scale of the disorder is larger than the propagating waves. Herzig Sheinfux
et al
. now show that a stack of several-nanometer-thick layers of
alternating high- and low-refractive- index material can result in the localization of
light. Such deep-subwavelength structures could provide a route to manipulating light on
the nanometer scale.

Science
, this issue p.
953
Redox stratification of an ancient lake in Gale crater, Mars
Authors: Hurowitz J. A. , Grotzinger J. P. , Fischer W. W. , McLennan S. M. , Milliken R. E. , Stein N. , Vasavada A. R. , Blake D. F. , Dehouck E. , Eigenbrode J. L. , Fairén A. G. , Frydenvang J. , Gellert R. , Grant J. A. , Gupta S. , Herkenhoff K. E. , Ming D. W. , Rampe E. B. , Schmidt M. E. , Siebach K. L. , Stack-Morgan K. , Sumner D. Y. , Wiens R. C.
Published: June 2017

The depths of an ancient lake on Mars

Gale crater on Mars was once a lake fed by rivers and groundwater. Hurowitz
et
al
. analyzed 3.5 years of data from the Curiosity rover’s exploration of
Gale crater to determine the chemical conditions in the ancient lake. Close to the
surface, there were plenty of oxidizing agents and rocks formed from large, dense
grains, whereas the deeper layers had more reducing agents and were formed from finer
material. This redox stratification led to very different environments in different
layers, which provides evidence for Martian climate change. The results will aid our
understanding of where and when Mars was once habitable.

Science
, this issue p.
eaah6849
A genetic signature of the evolution of loss of flight in the Galapagos cormorant
Authors: Burga Alejandro , Wang Weiguang , Ben-David Eyal , Wolf Paul C. , Ramey Andrew M. , Verdugo Claudio , Lyons Karen , Parker Patricia G. , Kruglyak Leonid
Published: June 2017

Loss of flight in the Galapagos cormorant

Although rare among existing birds, the loss of flight appears to have occurred multiple times in evolutionary history. However, the genetic changes that ground avian species are not well understood. Burgaet al. sequenced genomes from three cormorant species and compared them with that of the flightless Galapagos cormorant (see the Perspective by Cooper). They identified variants in genes involved in primary ciliogenesis. Functional analyses of these variants suggest that the impaired function of the genes may be responsible for skeletal changes associated with the Galapagos cormorant’s loss of flight.

Science, this issue p.eaal3345; see also p.904
Structural basis for antibody-mediated neutralization of Lassa virus
Authors: Hastie Kathryn M. , Zandonatti Michelle A. , Kleinfelter Lara M. , Heinrich Megan L. , Rowland Megan M. , Chandran Kartik , Branco Luis M. , Robinson James E. , Garry Robert F. , Saphire Erica Ollmann
Published: June 2017

The crystal structure of an antibody–viral glycoprotein complex illuminates viral entry mechanisms and provides a blueprint for vaccine design.
Entanglement distillation between solid-state quantum network nodes
Authors: Kalb N. , Reiserer A. A. , Humphreys P. C. , Bakermans J. J. W. , Kamerling S. J. , Nickerson N. H. , Benjamin S. C. , Twitchen D. J. , Markham M. , Hanson R.
Published: June 2017

A distillation protocol is developed that enhances entanglement between distant nodes of a quantum network.
A Cation-Binding Surface Protein as a Vaccine Antigen To Prevent Moraxella catarrhalis Otitis Media and Infections in Chronic Obstructive Pulmonary Disease
Authors: Murphy Timothy F. , Brauer Aimee L. , Johnson Antoinette , Wilding Gregory E. , Koszelak-Rosenblum Mary , Malkowski Michael G.
Published: June 2017

Moraxella catarrhalis
is an exclusively human respiratory tract pathogen that is a common cause of otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. A vaccine to prevent these infections would have a major impact on reducing the substantial global morbidity and mortality in these populations. Through a genome mining approach, we identified AfeA, an ∼32-kDa substrate binding protein of an ABC transport system, as an excellent candidate vaccine antigen. Recombinant AfeA was expressed and purified and binds ferric, ferrous, manganese, and zinc ions, as demonstrated by thermal shift assays. It is a highly conserved protein that is present in all strains of
M. catarrhalis
. Immunization with recombinant purified AfeA induces high-titer antibodies that recognize the native
M. catarrhalis
protein. AfeA expresses abundant epitopes on the bacterial surface and induces protective responses in the mouse pulmonary clearance model following aerosol challenge with
M. catarrhalis
. Finally, AfeA is expressed during human respiratory tract infection of adults with chronic obstructive pulmonary disease (COPD). Based on these observations, AfeA is an excellent vaccine antigen to be included in a vaccine to prevent infections caused by
M. catarrhalis
.
Transcriptional Profiling Confirms the Therapeutic Effects of Mast Cell Stabilization in a Dengue Disease Model
Authors: Morrison Juliet , Rathore Abhay P. S. , Mantri Chinmay K. , Aman Siti A. B. , Nishida Andrew , St. John Ashley L.
Published: June 2017

There are no approved therapeutics for the treatment of dengue disease despite the global prevalence of dengue virus (DENV) and its mosquito vectors. DENV infections can lead to vascular complications, hemorrhage, and shock due to the ability of DENV to infect a variety of immune and nonimmune cell populations. Increasingly, studies have implicated the host response as a major contributor to severe disease. Inflammatory products of various cell types, including responding T cells, mast cells (MCs), and infected monocytes, can contribute to immune pathology. In this study, we show that the host response to DENV infection in immunocompetent mice recapitulates transcriptional changes that have been described in human studies. We found that DENV infection strongly induced metabolic dysregulation, complement signaling, and inflammation. DENV also affected the immune cell content of the spleen and liver, enhancing NK, NKT, and CD8+T cell activation. The MC-stabilizing drug ketotifen reversed many of these responses without suppressing memory T cell formation and induced additional changes in the transcriptome and immune cell composition of the spleen, consistent with reduced inflammation. This study provides a global transcriptional map of immune activation in DENV target organs of an immunocompetent host and supports the further development of targeted immunomodulatory strategies to treat DENV disease.

IMPORTANCEDengue virus (DENV), which causes febrile illness, is transmitted by mosquito vectors throughout tropical and subtropical regions of the world. Symptoms of DENV infection involve damage to blood vessels and, in rare cases, hemorrhage and shock. Currently, there are no targeted therapies to treat DENV infection, but it is thought that drugs that target the host immune response may be effective in limiting symptoms that result from excessive inflammation. In this study, we measured the host transcriptional response to infection in multiple DENV target organs using a mouse model of disease. We found that DENV infection induced metabolic dysregulation and inflammatory responses and affected the immune cell content of the spleen and liver. The use of the mast cell stabilization drug ketotifen reversed many of these responses and induced additional changes in the transcriptome and immune cell repertoire that contribute to decreased dengue disease.
West Nile Virus NS1 Antagonizes Interferon Beta Production by Targeting RIG-I and MDA5
Authors: Zhang Hong-Lei , Ye Han-Qing , Liu Si-Qing , Deng Cheng-Lin , Li Xiao-Dan , Shi Pei-Yong , Zhang Bo
Published: June 2017

West Nile virus (WNV) is a mosquito-borne flavivirus that causes epidemics of encephalitis and viscerotropic disease worldwide. This virus has spread rapidly and has posed a significant public health threat since the outbreak in New York City in 1999. The interferon (IFN)-mediated antiviral response represents an important component of virus-host interactions and plays an essential role in regulating viral replication. Previous studies have suggested that multifunctional nonstructural proteins encoded by flaviviruses antagonize the host IFN response via various means in order to establish efficient viral replication. In this study, we demonstrated that the nonstructural protein 1 (NS1) of WNV antagonizes IFN-β production, most likely through suppression of retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) activation. In a dual-luciferase reporter assay, WNV NS1 significantly inhibited the activation of the IFN-β promoter after Sendai virus infection or poly(I·C) treatment. NS1 also suppressed the activation of the IFN-β promoter when it was stimulated by interferon regulatory factor 3 (IRF3)/5D or its upstream molecules in the RLR signaling pathway. Furthermore, NS1 blocked the phosphorylation and nuclear translocation of IRF3 upon stimulation by various inducers. Mechanistically, WNV NS1 targets RIG-I and melanoma differentiation-associated gene 5 (MDA5) by interacting with them and subsequently causing their degradation by the proteasome. Furthermore, WNV NS1 inhibits the K63-linked polyubiquitination of RIG-I, thereby inhibiting the activation of downstream sensors in the RLR signaling pathway. Taken together, our results reveal a novel mechanism by which WNV NS1 interferes with the host antiviral response.

IMPORTANCE
WNV Nile virus (WNV) has received increased attention since its introduction to the United States. However, the pathogenesis of this virus is poorly understood. This study demonstrated that the nonstructural protein 1 (NS1) of WNV antagonizes the induction of interferon beta (IFN-β) by interacting with and degrading retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5), which are crucial viral sensors in the host innate immune system. Further experiments suggested that NS1-mediated inhibition of the RIG-I-like receptor (RLR) signaling pathway involves inhibition of RIG-I K63-linked polyubiquitination and that the proteasome plays a role in RIG-I degradation. This study provides new insights into the regulation of WNV NS1 in the RLR signaling pathway and reveals a novel mechanism by which WNV evades the host innate immune response. The novel findings may guide us to discover new therapeutic targets and develop effective vaccines for WNV infections.
Incidence, risk factors and management of intractable diplopia
Authors: Newsham David , O’Connor Anna R , Harrad Richard A
Published: June 2017

Aims

There is a paucity of literature concerning intractable diplopia. The aims of this study were to determine the incidence of intractable diplopia in the UK, identify the causes and any associated risk factors, establish how cases are managed and if the treatment is successful and tolerated.

Methods

A 1-year prospective observational study was undertaken via the British Ophthalmological Surveillance Unit (BOSU). This involved implementation of a reporting mechanism, which then triggered distribution of an incident questionnaire to explore clinical details concerning each case and a follow-up questionnaire 6 months later to explore how the case had been managed.

Results

The incidence of intractable diplopia was 53 cases per year. The most common preceding events were strabismus surgery (32%), no known preceding event, that is,spontaneous (25%), severe head trauma (8%), cataract surgery (6%) and vitrectomy (6%). In the at-risk age group of 7 years and above, the incidence of intractable diplopia following strabismus surgery is 1 in 494 (95% CI; 1 in 296 to 790) cases. A total of nine different treatments were used in the management, with many patients receiving between two and four different methods. The overall success rate was poor, but most effective were opaque intraocular lenses (IOLs) (86%) and opaque contact lenses (50%).

Conclusion

Intractable diplopia is a relatively rare but important condition. The main risk factor is a pre-existing strabismus, and careful counselling is needed when planning surgical correction in patients with no demonstrable binocular function. Treatment success of intractable diplopia is high when using opaque IOLs, although with additional risk, but is often disappointing via other methods where it can be difficult to eradicate the diplopia successfully.
Primary enucleation for group D retinoblastoma in the era of systemic and targeted chemotherapy: the price of retaining an eye
Authors: Fabian Ido D , Stacey Andrew W , Johnson Kenneth C , Chowdhury Tanzina , Duncan Catriona , Reddy M Ashwin , Sagoo Mandeep S
Published: June 2017

Background

Chemotherapy is increasingly used as primary treatment for group D retinoblastoma, whereas primary enucleation is considered to have a diminishing role. This study aimed to compare the management course, including number of examinations under anaesthesia (EUAs), of group D patients treated by enucleation versus chemotherapy.

Methods

A retrospective analysis of 92 group D patients, of which 40 (37 unilateral) underwent primary enucleation and 52 (17 unilateral) were treated with intravenous chemotherapy. Number of EUAs was compared between the treatment groups with respect to the whole cohort, using univariate and multivariate analysis, and to unilateral cases only.

Results

Patients were followed up for a median of 61 months (mean: 66, range: 14–156), in which time primary enucleated patients had on average seven EUAs and chemotherapy-treated patients 21 EUAs (p<0.001). Chemotherapy, young age, bilateral disease, multifocal tumours, familial and germline retinoblastoma were found on univariate analysis to correlate with increased number of EUAs (p≤0.019). On multivariate analysis, however, only treatment type and presentation age were found significant (p≤0.001). On subanalysis of the unilateral cases, patients undergoing primary enucleation had in average seven EUAs, as compared with 16 in the chemotherapy group (p<0.001). Of the 55 unilateral-presenting patients, a new tumour developed in the fellow eye only in a single familial case.

Conclusion

Group D patients’ families should be counselled regarding the significant difference in number of EUAs following primary enucleation versus chemotherapy when deciding on a treatment strategy. In this regard, primary enucleation would be most beneficial for older patients with unilateral disease.
Randomised controlled trial of transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND Study)
Authors: Barendse Renée M , Musters Gijsbert D , de Graaf Eelco J R , van den Broek Frank J C , Consten Esther C J , Doornebosch Pascal G , Hardwick James C , de Hingh Ignace H J T , Hoff Chrisiaan , Jansen Jeroen M , van Milligen de Wit A W Marc , van der Schelling George P , Schoon Erik J , Schwartz Matthijs P , Weusten Bas L A M , Dijkgraaf Marcel G , Fockens Paul , Bemelman Willem A , Dekker Evelien
Published: June 2017

Objective

Non-randomised studies suggest that endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM), but EMR might be more cost-effective and safer. This trial compares the clinical outcome and cost-effectiveness of TEM and EMR for large rectal adenomas.

Design

Patients with rectal adenomas ≥3 cm, without malignant features, were randomised (1:1) to EMR or TEM, allowing endoscopic removal of residual adenoma at 3 months. Unexpected malignancies were excluded postrandomisation. Primary outcomes were recurrence within 24 months (aiming to demonstrate non-inferiority of EMR, upper limit 10%) and the number of recurrence-free days alive and out of hospital.

Results

Two hundred and four patients were treated in 18 university and community hospitals. Twenty-seven (13%) had unexpected cancer and were excluded from further analysis. Overall recurrence rates were 15% after EMR and 11% after TEM; statistical non-inferiority was not reached. The numbers of recurrence-free days alive and out of hospital were similar (EMR 609±209, TEM 652±188, p=0.16). Complications occurred in 18% (EMR) versus 26% (TEM) (p=0.23), with major complications occurring in 1% (EMR) versus 8% (TEM) (p=0.064). Quality-adjusted life years were equal in both groups. EMR was approximately €3000 cheaper and therefore more cost-effective.

Conclusion

Under the statistical assumptions of this study, non-inferiority of EMR could not be demonstrated. However, EMR may have potential as the primary method of choice due to a tendency of lower complication rates and a better cost-effectiveness ratio. The high rate of unexpected cancers should be dealt with in further studies.
A Broad Case-Based Distance Approach for Screening with Different Target Points
Authors: Ma Li-Ching
Published: June 2017

The case-based distance (CBD) methods for screening are helpful for assisting decision makers in filtering out alternatives that are unlikely to be chosen. However, most of these methods based on selected cases and distance measurements from a chosen target point can only solve screening problems with positive criteria weights. This study proposes a two-phase approach based on mixed integer programming to integrate the concept of Data Envelopment Analysis-Discriminant Analysis (DEA-DA) and the extended case-based distance (ECBD) method for screening problems involving uncertain signs of criteria weights and different target points. The results show that the proposed approach can reduce the misclassification rate and address multiple solution problems. In addition, because the proposed approach can solve problems involving negative weights directly, the influences of different target points can be reduced. Therefore, it is helpful for decision makers to conduct scenario analysis based on different chosen target points.
Colonic Histological Criteria Predict Development of Pouchitis after Ileal Pouch: Anal Anastomosis for Patients with Ulcerative Colitis
Authors: Araki Toshimitsu , Hashimoto Kiyoshi , Okita Yoshiki , Fujikawa Hiroyuki , Kondo Satoru , Kobayashi Minako , Ohi Masaki , Toiyama Yuji , Inoue Yasuhiro , Uchida Keiichi , Mohri Yasuhiko , Kusunoki Masato
Published: June 2017

Background/Aims: Pouchitis is one of the main complications after ileal pouch-anal anastomosis in patients with ulcerative colitis. The aim of this study was to determine whether the use of colonic histological criteria can predict the development of pouchitis. Methodology: We retrospectively reviewed 147 patients' clinical data and performed a histological evaluation of the resected total colon using Tanaka's criteria, which comprise the following 6 factors: ulceration (H1), crypt abscesses (H2), degree of mononuclear cell infiltration (MNCI) (H3), segmental distribution of MNCI (H4), eosinophil infiltration (H5), and extent of disease of resected colon (H6). Results: The development of pouchitis and chronic pouchitis within 3 years after restoration of gastrointestinal continuity was recognized in 52 (35.4%) and 26 (17.7%) of the 147 patients, respectively. Using various combinations of each score, the H3 + H4 - H5 scores of patients with pouchitis or chronic pouchitis were significantly higher than those of patients without. A H3 + H4 - H5 score of >0.4 was a statistically significant risk factor for the development of both pouchitis and chronic pouchitis. Conclusions: The combination of the degree of MNCI, segmental distribution of MNCI, and eosinophil infiltration from histological criteria has utility in predicting the future development of pouchitis, especially chronic pouchitis.