bluuebunny/crossref_metadata_2025 huggingface dataset:
Smut infection of perennial hosts: the genome and the transcriptome of the Brassicaceae smut fungus Thecaphora thlaspeos reveal functionally conserved and novel effectors
Authors: Courville Kaitlyn J. , Frantzeskakis Lamprinos , Gul Summia , Haeger Natalie , Kellner Ronny , Heßler Natascha , Day Brad , Usadel Björn , Gupta Yogesh K. , van Esse H. Peter , Brachmann Andreas , Kemen Eric , Feldbrügge Michael , Göhre Vera
Published: January 2019

Biotrophic fungal plant pathogens can balance their virulence and form intricate relationships with their hosts. Sometimes, this leads to systemic host colonization over long time scales without macroscopic symptoms. However, how plant‐pathogenic endophytes manage to establish their sustained systemic infection remains largely unknown.

Here, we present a genomic and transcriptomic analysis of Thecaphora thlaspeos. This relative of the well studied grass smut Ustilago maydis is the only smut fungus adapted to Brassicaceae hosts. Its ability to overwinter with perennial hosts and its systemic plant infection including roots are unique characteristics among smut fungi.

The T. thlaspeos genome was assembled to the chromosome level. It is a typical smut genome in terms of size and genome characteristics. In silico prediction of candidate effector genes revealed common smut effector proteins and unique members. For three candidates, we have functionally demonstrated effector activity. One of these, TtTue1, suggests a potential link to cold acclimation. On the plant side, we found evidence for a typical immune response as it is present in other infection systems, despite the absence of any macroscopic symptoms during infection.

Our findings suggest that T. thlaspeos distinctly balances its virulence during biotrophic growth ultimately allowing for long‐lived infection of its perennial hosts.
Specification Searching and Significance Inflation Across Time, Methods and Disciplines
Authors: Vivalt Eva
Published: January 2019

This paper examines how significance inflation has varied across time, methods and disciplines. Leveraging a unique data set of impact evaluations on 20 kinds of development programmes, I find that results from randomized controlled trials exhibit less significance inflation than results from studies using other methods. Further, randomized controlled trials have exhibited less significance inflation over time, but quasi‐experimental studies have not. There is no robust difference between results from researchers affiliated with economics departments and those from researchers affiliated with other predominantly health‐related departments. Overall, the biases found appear much smaller than those previously observed in other social sciences.
Alignment efficiency of coaxial tubular superelastic nickel‐titanium vs single‐stranded superelastic nickel‐titanium in relieving mandibular anterior crowding in extraction cases: A single‐centre randomized controlled clinical trial
Authors: Sebastian Biju , Abraham Merin Elsa , Sarma Prabhakaran Sankara , Cherian Karun Koshy
Published: January 2019

Structured Abstract

Objectives

To compare the alignment efficiency of coaxial tubular and single‐stranded 0.016” superelastic NiTi archwires in relieving mandibular anterior crowding in extraction cases and to evaluate whether alignment efficiency differed as the initial irregularity increased.

Setting and Sample Population

Forty female patients aged between twelve and twenty years from the postgraduate orthodontic clinic at the authors’ centre.

Materials and Methods

All patients in this single‐centre, 2‐arm parallel trial were randomly allocated in a 1:1 ratio and the mandibular anterior irregularity was measured from the mandibular cast at 0‐, 4‐, 8‐ and 12‐week intervals using a digital calliper.

Results

All forty patients (mean age, 15.08 ± 2.11) completed the study with either coaxial tubular superelastic NiTi (mean age, 15.30 ± 2.36) or single‐stranded superelastic NiTi (mean age, 14.85 ± 1.84). The largest mean irregularity index reduction of −4.88 ± 2.74 and −6.17 ± 2.38 in the single‐stranded superelastic NiTi and the coaxial tubular superelastic NiTi groups, respectively (P = 0.122) was at 4 weeks. Student's t test and repeated measures ANOVA indicated that none of the mean comparisons were statistically significant at a 5% level. Pearson's correlation value (r) indicated no statistically significant influence of initial crowding on alignment efficiency.

Conclusions

There was no statistically significant difference between the alignment efficiency of coaxial tubular superelastic NiTi and single‐stranded superelastic NiTi in extraction cases, and the degree of initial crowding had no influence on the alignment efficiency.
Same or Different? An Aesthetic Design Question
Authors: Li Krista J. , Liu Yan
Published: January 2019

Should brands selling status goods design high‐end and low‐end products to look the same or different? In this paper, we study how brands make this aesthetic design differentiation decision. We first empirically analyze the impact of a brand’s aesthetic design differentiation on consumers’ preferences for the brand’s products using seven years of data of a status good (i.e., cars). We find that consumers prefer high‐end products of a brand to look more differentiated but prefer low‐end products of the brand to look less differentiated, which seems to present brands a product design dilemma, that is, neither design unification nor diversification within a brand can enhance the appeal of the brand’s high‐end and low‐end products at the same time. Based on this finding, we set up a game‐theoretic model to analyze brands’ equilibrium design strategies. Interestingly, we find that the opposing preferences for design differentiation can lead brands to choose asymmetric design strategies, that is, one brand unifies design while another brand diversifies design, which can be a win–win outcome. We also give conditions where both brands unify design or both brands diversify design while the latter can be a prisoner’s dilemma. Furthermore, vertical differentiation (e.g., in brand strength) between brands affects the profitability of design diversification or unification. In addition, we show that the aesthetic design decision has important implications on how brands should set prices and functionalities of products and how much brands should invest in brand‐building activities (e.g., advertising).
Caffeine affects children’s ERPs and performance in an equiprobable go/no‐go task: Testing a processing schema
Authors: Barry Robert J. , De Blasio Frances M. , Fogarty Jack S.
Published: January 2019

Caffeine’s stimulant properties were used to test a proposed processing schema for children’s processing stages in the equiprobable auditory go/no‐go task. Active control‐related ERP components were hypothesized to be differentially enhanced by caffeine. Caffeine (80 mg) was administered in a counterbalanced, randomized, double‐blind, placebo‐controlled, cross‐over study of 24 children, aged 8–12 years. Four blocks of an equiprobable auditory go/no‐go task were completed on each of two occasions, while on or off caffeine. ERP data sets from each condition (caffeine/go, placebo/go, caffeine/no‐go, placebo/no‐go) were subjected to separate temporal PCAs with extraction and varimax rotation of all components. Caffeine significantly reduced reaction time and go omission errors, and enhanced go PN, N2c, and P3b, and no‐go N1‐1 and N2b. This selective enhancement of different go/no‐go components by caffeine matched the predicted amplification of biomarkers of children’s active control processing in this task. Some unexpected findings also support further refinements in the child processing schema.
Out and about: Subsequent memory effect captured in a natural outdoor environment with smartphone EEG
Authors: Piñeyro Salvidegoitia Maria , Jacobsen Nadine , Bauer Anna‐Katharina R. , Griffiths Benjamin , Hanslmayr Simon , Debener Stefan
Published: January 2019

Spatiotemporal context plays an important role in episodic memory. While temporal context effects have been frequently studied in the laboratory, ecologically valid spatial context manipulations are difficult to implement in stationary conditions. We investigated whether the neural correlates of successful encoding (subsequent memory effect) can be captured in a real‐world environment. An off‐the‐shelf Android smartphone was used for wireless mobile EEG acquisition and stimulus presentation. Participants encoded single words, each of which was presented at a different location on a university campus. Locations were approximately 10–12 m away from each other, half of them with striking features (landmarks) nearby. We predicted landmarks would improve recall performance. After a first free recall task of verbal stimuli indoors, participants performed a subsequent recall outdoors, in which words and locations were recalled. As predicted, significantly more words presented at landmark locations as well as significantly more landmark than nonlandmark locations were recalled. ERP analysis yielded a larger posterior positive deflection during encoding for hits compared to misses in the 400–800 ms interval. Likewise, time‐frequency analysis revealed a significant difference during encoding for hits compared to misses in the form of stronger alpha (200–300 ms) and theta (300–400 ms) power increases. Our results confirm that a vibrant spatial context is beneficial in episodic memory processing and that the underlying neural correlates can be captured with unobtrusive smartphone EEG technology. The advent of mobile EEG technology promises to unveil the relevance of natural physical activity and natural environments on memory.
Differences in embryonic gene expression and quality indicate the benefit of epidermal growth factor receptor inhibitor during prematuration to improve competence in bovine oocytes
Authors: Chediek Dall’Acqua Priscila , Barros Nunes Giovana , Rodrigues da Silva Cíntia , Fontes Patrícia Kubo , Fábio Gouveia Nogueira Marcelo , Lombardi Lopes Flávia , Marinho Márcia , Zoccal Mingoti Gisele
Published: January 2019

Contents

The epidermal growth factor receptor (EGFR) pathway is directly involved in oocyte meiotic resumption induced by a gonadotropic stimulus. Here, we used an EGFR inhibitor (AG1478) to inhibit spontaneous meiosis resumption in bovine oocytes (EGFR− group) during 8 hr prematuration and assessed the competence of such oocytes for embryonic development, apoptosis and gene expression in comparison with Control group which was not prematured. Data are presented as mean ± SEM. Blastocysts rate on day 7 (40.81%, averaged) and hatching rate on day 9 (77.35%, averaged) were unaffected by treatment (p > 0.05). Similarly, treatment did not affect (p > 0.05) the total cell number on day 7 (119.05, averaged) and on day 9 (189.5, averaged). Apoptosis was reduced (p < 0.05) in EGFR− group day 7‐embryos compared to Control group (3.7% ± 1.0 vs. 5.2% ± 0.8). Abundance of several transcripts was upregulated (p < 0.05) in EGFR− group, including genes related to embryo development and quality (NANOG and RPLP0), epigenetic regulation (H2AFZ), apoptosis (BID) and stress response (GPX4 and HIF1A). Taken together, the results presented here demonstrated a reduction in the apoptosis index and upregulation of NANOG, H2AFZ and RPLP0 mRNA levels, which are related to embryonic development. Our data suggest that temporary meiosis blockage with EGFR inhibitor during prematuration culture of bovine oocytes may be an interesting strategy to improve embryo quality.
Edge detector‐based automatic segmentation of the skin layers and application to moisturization in high‐resolution 3 Tesla magnetic resonance imaging
Authors: Ognard Julien , Mesrar Jawad , Benhoumich Younes , Misery Laurent , Burdin Valerie , Ben Salem Douraied
Published: January 2019

Introduction

Previous studies have demonstrated the feasibility to explore moisturization with quantification imaging based on T2 mapping. The aim of this study was to describe and validate the first robust automated method to segment the first layers of the skin.

Materials and Methods

Data were picked from a previous study that included 35 healthy subjects who underwent a 3T MRI (multi spin echo calculation T2‐weighted sequence) with a microscopic coil on the left heel before and one hour after moisturization. The automatic algorithm was composed of the T2 map generation, a Canny filter, a selection of boundaries, and a local regression to delimitate stratum corneum, epidermis, and dermis. An automated affine registration was applied between the exams before and after moisturization.

Results

The failure rate of the algorithm was below 5%. Mean computation time was 139.12s. There was a significant and strong correlation between the automatic measurements and the manual ones for the T2 values (ρ: 0.905, P < 0.001) and for the thickness measurements (ρ: 0.8663; P < 0.001). For registration, mean of the Dice index was 0.64 [0.47; 0.80] and of the Hausdorff distance was 0.29 mm 95% CI: [0.28; 0.30].

Conclusion

The proposed automatic method to study the first skin layers in 3T MRI using micro‐coils was robust and described T2 values and thickness measurements with a strong correlation to manual measurements. The use of an automated affine registration could also permit the generation of a mapping for a visual assessment of moisturization.
Impact of cumulative steroid dose on infectious diseases after allogenic hematopoietic stem cell transplantation
Authors: Watanabe Mizuki , Kanda Junya , Hishizawa Masakatsu , Kondo Tadakazu , Yamashita Kouhei , Takaori‐Kondo Akifumi
Published: January 2019

Background

Systemic steroid is used to treat various transplant‐related complications after allogenic hematopoietic stem cell transplantation (allo‐HSCT). However, measures to evaluate its impact on infections are still limited. Hence, we examined the cumulative steroid dose used within 30 days after transplant as a predictor of future risk of infections.

Methods

This study included 226 patients who underwent their first allo‐HSCT at Kyoto University Hospital between 2005 and 2015.

Results

Sixty‐one patients received transplantation from related donors, 106 received unrelated BMT and 59 received unrelated single‐unit CBT. Patients were categorized into three groups according to the cumulative steroid dose in terms of prednisolone: no‐steroid group (n = 174), low‐dose group (≤7 mg/kg) (n = 22) and high‐dose group (>7 mg/kg) (n = 30). In a multivariate analysis, high‐dose steroid administration was associated with cytomegalovirus (CMV) antigenemia (HR 1.91, P = 0.037) and bacteremia (HR 2.59, P = 0.053). No impact was found on the occurrence of invasive fungal infection.

Conclusion

High‐dose cumulative steroid could predict high risks of bacteremia and CMV antigenemia. Additional anti‐bacterial agents for fever and regular measurement of CMV antigen are recommended for whom with systemic steroid administration even after neutrophil engraftment.
A multi‐level response to DNA damage induced by aluminium
Authors: Chen Poyu , Sjogren Caroline A. , Larsen Paul B. , Schnittger Arp
Published: January 2019

Aluminium (Al) ions are one of the primary growth‐limiting factors for plants on acid soils, globally restricting agriculture. Despite its impact, little is known about Al action in planta. Earlier work has indicated that, among other effects, Al induces DNA damage. However, the loss of major DNA damage response regulators, such SOG1, partially suppressed the growth reduction in plants seen on Al‐containing media. This raised the question whether Al actually causes DNA damage and, if so, how. Here, we provide cytological and genetic data corroborating that exposure to Al leads to DNA double‐strand breaks. We find that the Al‐induced damage specifically involves homology‐dependent (HR) recombination repair. Using an Al toxicity assay that delivers higher Al concentrations than used in previous tests, we find that sog1 mutants become highly sensitive to Al. This indicates a multi‐level response to Al‐induced DNA damage in plants.
Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 5—Discontinuation of anticoagulant therapy in small animals
Authors: Brainard Benjamin M. , Buriko Yekaterina , Good Jennifer , Ralph Alan G. , Rozanski Elizabeth A.
Published: January 2019

Objectives

To systematically evaluate the evidence supporting the timing and mechanisms of permanent or temporary discontinuation of antiplatelet or anticoagulant medications in small animals

Design

Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence and quality (poor, fair, or good), and development of consensus on conclusions via a Delphi‐style survey for application of the concepts to clinical practice.

Settings

Academic and referral veterinary medical centers.

Results

Databases searched included Medline via PubMed and CAB abstracts. Two specific courses of inquiry were pursued, one focused on appropriate approaches to use for small animal patients receiving antiplatelet or anticoagulant drugs and requiring temporary discontinuation of this therapy for the purposes of invasive procedures (eg, surgery), and the other aimed at decision‐making for the complete discontinuation of anticoagulant medications. In addition, the most appropriate methodology for discontinuation of heparins was addressed.

Conclusions

To better define specific patient groups, a risk stratification characterization was developed. It is recommended to continue anticoagulant therapy through invasive procedures in patients at high risk for thrombosis that are receiving anticoagulant therapy, while consideration for discontinuation in patients with low to moderate risk of thrombosis is reasonable. In patients with thrombosis in whom the underlying cause for thrombosis has resolved, indefinite treatment with anticoagulant medication is not recommended. If the underlying cause is unknown or untreatable, anticoagulant medication should be continued indefinitely. Unfractionated heparin therapy should be slowly tapered rather than discontinued abruptly.
Improved visualization of the lumbar spine nerve roots in dogs using water excitation (ProSet) as opposed to short tau inversion recovery: A retrospective study of two fat suppression MRI sequences
Authors: Bergamino Chiara , Hoey Séamus E. , de Swarte Marie , Skelly Cliona
Published: January 2019

Magnetic resonance imaging fat suppression techniques are commonly used for diagnosis of canine spinal disease, however, studies comparing different techniques are currently lacking. This retrospective, methods comparison study aimed to evaluate water excitation and STIR MRI pulse sequences for visualization of canine lumbar spinal nerve roots. For inclusion, all dogs had to have dorsal planar MRI studies of the lumbar spine using both sequences. Visual grading analysis was used for scoring the following five criteria: degree of fat suppression; nerve root visualization; subjective tissue contrast; presence of noise; and overall better image quality. Scores were independently recorded by three board‐certified veterinary radiologists on two separate occasions, 3‐6 weeks apart. A total of 90 dogs were sampled. A two‐tailedt‐test showed that there were significant differences in all scored parameters (P < 0.00001), with the exception of noise (P = 0.47343), and that the water excitation sequence scored higher in all cases excluding noise. A Gwets AC kappa for intraobserver and interobserver reliability showed “almost perfect” agreement for the nerve roots in both tests (intra:k = 0.88; inter:k = 0.90). Intraobserver agreement was “substantial” for the degree of fat suppression (k = 0.68), subjective tissue contrast (k = 0.75), and overall better image quality (k = 0.76) and it was “fair” for the noise (k = 0.46). Interobserver agreement was “moderate” for the degree of fat suppression (k = 0.53), subjective tissue contrast (k = 0.63), and overall better image quality (k = 0.66) and “slight” for noise (k = 0.25). These findings supported using the water excitation pulse sequence for fat‐suppressed MRI of canine lumbar spinal nerve roots.
ARE WE CLOSER TO FREE MARKET EUGENICS? THE CRISPR CONTROVERSY
Authors: Peters Ted
Published: January 2019

Might the 2018 birth of two designer babies in China write the opening paragraph for the next chapter in the history of eugenics? The worldwide scientific community has tacitly put a moratorium on human clinical application of CRISPR gene editing, waiting until unknown risks can become known. But this ethical agreement has been breached, and calls are now being heard for more rigorous regulations. Perhaps religious and spiritual leaders can join the bioethical chant: the yellow light of caution is flashing.
Investigation of Hyperactivity and Attention Deficit of University Students Who Do Sport Regularly and Do Not Do Sport in Terms Of Some Variances
Authors: Özkan Zekiye , Arslan Ersin
Published: January 2019

Introduction: Hyperactivity and attention deficit are situations which have been seen in individuals recently and affect both academic and life quality of individual negatively. The aim of this study is to determine hyperactivity and attention deficit level of university student who sport regularly and do not sport.Method: Carried out with scanning model, this study was applied to 353 students, who continue their education at Yuzuncu Yil University during 2017/2018 academic year, including 208 students who sport regularly and 145 students who do not sport. Reliability and validity of Turkish form of WHO’s Adult Attention Deficit/Hyperactivity Disorder Self-Report Scale (ASRS-v1.1) was carried out by Dogan et. al. (2009). As statistical method, as well as descriptive statistics, Kruskal Wallis H test for multiple comparisons and Mann-Whitney U test for paired comparisons were used in the situations in which normality and homogeneity of variances were not provided. p<0.05 was determined as significance level.Findings: When attention deficit (p<0.01) and hyperactivity (p<0.05) levels in those who do sport and those who do not do sport were examined, significant difference was found in favor of those who do sport. In examination of hyperactivity levels and attention deficit in terms of academic success, it was found that there was a significant difference in favor of those who have higher academic success (p<0.05). When hyperactivity levels and attention deficit were analyzed in terms of participants’ sheltering status, a significant difference was seen in favor of those who stay in a house far from their family (p<0.05). A significant difference in terms of high school from which participants graduated and in terms of their parents’ education level (p>0.05).Conclusion: It has been seen that hyperactivity levels and attention deficit of university students are related to many factors. Today, intensely usage of technology affects individuals negatively. Moreover, it has been found that attention deficit and hyperactivity levels are high in those individuals who do not do sport regularly.
Feeling Newton’s Second Law
Authors: Coletta Vincent P. , Bernardin Josh , Pascoe Daniel , Hoemke Anatol
Published: January 2019

Physics instructors recognize the value of kinesthetic experience in learning fundamental physics concepts. We describe a kinesthetic experiment appropriate for both college and high school physics students. The experiment helps students achieve an intuitive understanding of Newton’s second law in a way they find quite enjoyable. It was devised by one of us over 20 years ago and has been performed by thousands of students at Loyola Marymount University (LMU) and by students at some Los Angeles area high schools. Next Generation Science Standards (NGSS) call for high school students to be able to analyze and interpret data and to understand Newton’s second law, which are central to this experiment. The experiment gives students a feel for Newton’s second law by requiring them to adjust their own motion so that they move at constant acceleration in order to maintain a constant force on a cart carrying a second student.
Electromagnetic Induction and Lenz’s Law Revisited
Authors: Behroozi F.
Published: January 2019

Many of the old demonstrations in electricity and magnetism can be performed more effectively and with greater visual appeal by using newly available neodymium magnets and color LEDs. For this reason several demonstrations, commonly used for teaching electromagnetic induction and Lenz’s law, have received renewed attention in recent years. In particular strong neodymium magnets have been used in several new demonstrations and experiments to help students learn the subtleties of eddy currents and magnetic braking. Here we describe several demonstrations that use a strong neodymium magnet, a coil, and a few LEDs to teach students in introductory physics the fundamentals of electromagnetic induction. More importantly the addition of LEDs provides a visual demonstration of Lenz’s law, with which many students have some difficulty. The demonstrations described here are quite simple to construct, fun to do, and visually appealing; they may be used either in the laboratory or in the classroom.
Tympanic membrane surface motions in forward and reverse middle ear transmissions
Authors: Cheng Jeffrey Tao , Maftoon Nima , Guignard Jérémie , Ravicz Michael E. , Rosowski John
Published: January 2019

Characterization of Tympanic Membrane (TM) surface motions with forward and reverse stimulation is important to understanding how the TM transduces acoustical and mechanical energy in both directions. In this paper, stroboscopic opto-electronic holography is used to quantify motions of the entire TM surface induced by forward sound and reverse mechanical stimulation in human cadaveric ears from 0.25 to 18.4 kHz. The forward sound stimulus was coupled to an anatomically realistic artificial ear canal that allowed optical access to the entire TM surface, and the reverse mechanical stimulus was applied to the body of the incus by a piezo-electric stimulator. The results show clear differences in TM surface motions evoked by the two stimuli. In the forward case, TM motion is dominated by standing-wave-like modal motions that are consistent with a relatively uniform sound-pressure load over the entire TM surface. With reverse mechanical stimulation, the TM surface shows more traveling waves, consistent with a localized mechanical drive applied to the manubrium embedded in the TM. With both stimuli, the manubrium moves less than the rest of the TM, consistent with the TM acting like a compliant membrane rather than a stiff diaphragm, and also consistent with catenary behavior due to the TM's curved shape.
Deposition of polydisperse gas suspensions with nonlinear resonance oscillations in a closed tube
Authors: Gubaidullin Damir A. , Zaripov Rinat G. , Tkachenko Liudmila A. , Shaidullin Linar R.
Published: January 2019

The characteristics of the deposition of a polydisperse gas suspension (tobacco smoke) in a closed tube in the mode of transition to shock waves at the first natural frequency are studied experimentally. The natural deposition of tobacco smoke continues for a long time. When the oscillations are excited, the process occurs hundreds of times faster. The shortest time for the deposition of tobacco smoke takes place when the tube is half filled. When filling the tube by a quarter and three quarters, the time of the process is almost the same, despite the three-fold difference in the content of smoke in the tube. Thus, the dependence of the tobacco smoke deposition time on the tube filling height is not monotone, which is associated with the formation of a secondary flow in the form of two toroidal vortices in the upper and lower halves of the closed tube.
Pain spreads from shutdown
Authors: Malakoff David
Published: January 2019

Historic spending impasse halts paychecks and projects.
The brain's traffic problems
Authors: Dolgin Elie
Published: January 2019

Disrupted flow into and out of the nucleus may kill neurons.
A Eu
3+
-Eu
2+
ion redox shuttle imparts operational durability to Pb-I perovskite solar cells
Authors: Wang Ligang , Zhou Huanping , Hu Junnan , Huang Bolong , Sun Mingzi , Dong Bowei , Zheng Guanghaojie , Huang Yuan , Chen Yihua , Li Liang , Xu Ziqi , Li Nengxu , Liu Zheng , Chen Qi , Sun Ling-Dong , Yan Chun-Hua
Published: January 2019

A redox road to recovery

Device longevity is a key issue for organic-inorganic perovskite solar cells. Encapsulation can limit degradation arising from reactions with oxygen and water, but light, electric-field, and thermal stresses can lead to metastable elemental lead and halide atom defects. Wang
et al.
show that for the lead-iodine system, the introduction of the rare earth europium ion pair Eu
3+
-Eu
2+
can shuttle electrons and recover lead and iodine ions (Pb
2+
and I
−
). Devices incorporating this redox shuttle maintained more than 90% of their initial power conversion efficiencies under various aging conditions.

Science
, this issue p.
265
B cells, CMV, and stem cell transplant
Authors: Alegre Maria-Luisa
Published: January 2019

Host antibodies help prevent CMV dissemination after bone marrow transplantation
Gene therapy for pathologic gene expression
Authors: Montefiori Lindsey E. , Nobrega Marcelo A.
Published: January 2019

Haploinsufficiency in disease can be overcome by boosting gene expression with CRISPR
The cerebellum gets social
Authors: D'Angelo Egidio
Published: January 2019

The cerebellum can regulate behavior by controlling dopamine release
Early Detection of Emergent Extensively Drug-Resistant Tuberculosis by Flow Cytometry-Based Phenotyping and Whole-Genome Sequencing
Authors: O’Donnell Max R. , Larsen Michelle H. , Brown Tyler S. , Jain Paras , Munsamy Vanisha , Wolf Allison , Uccellini Lorenzo , Karim Farina , de Oliveira Tulio , Mathema Barun , Jacobs William R. , Pym Alexander
Published: January 2019

A critical gap in tuberculosis (TB) treatment is detection of emergent drug resistance. We hypothesized that advanced phenotyping with whole-genome sequencing (WGS) will detect low-frequency
Mycobacterium tuberculosis
drug resistance.
Uncoupled Quorum Sensing Modulates the Interplay of Virulence and Resistance in a Multidrug-Resistant Clinical
Pseudomonas aeruginosa
Isolate Belonging to the MLST550 Clonal Complex
Authors: Cao Huiluo , Xia Tingying , Li Yanran , Xu Zeling , Bougouffa Salim , Lo Yat Kei , Bajic Vladimir B. , Luo Haiwei , Woo Patrick C. Y. , Yan Aixin
Published: January 2019

Pseudomonas aeruginosa
is a prevalent and pernicious pathogen equipped with extraordinary capabilities both to infect the host and to develop antimicrobial resistance (AMR). Monitoring the emergence of AMR high-risk clones and understanding the interplay of their pathogenicity and antibiotic resistance is of paramount importance to avoid resistance dissemination and to control
P. aeruginosa
infections.
Efficacy of Tedizolid against Enterococci and Staphylococci, Including
cfr
+
Strains, in a Mouse Peritonitis Model
Authors: Singh Kavindra V. , Arias Cesar A. , Murray Barbara E.
Published: January 2019

In a mouse peritonitis model, tedizolid was comparable to linezolid and daptomycin against an
Enterococcus faecium
strain (VAN
r
, AMP
r
), an
Enterococcus faecalis
strain, and a methicillin-resistant
Staphylococcus aureus
(MRSA) strain with and without
cfr
. Against a
cfr
(B)
+
E. faecium
, tedizolid was inferior
in vivo
to linezolid and daptomycin, despite an ∼4-fold lower MIC.
Redundant and Distinct Roles of Secreted Protein Eap and Cell Wall-Anchored Protein SasG in Biofilm Formation and Pathogenicity of Staphylococcus aureus
Authors: Yonemoto Keigo , Chiba Akio , Sugimoto Shinya , Sato Chikara , Saito Mitsuru , Kinjo Yuki , Marumo Keishi , Mizunoe Yoshimitsu
Published: January 2019

Chronic and fatal infections caused by
Staphylococcus aureus
are sometimes associated with biofilm formation. Secreted proteins and cell wall-anchored proteins (CWAPs) are important for the development of polysaccharide-independent biofilms, but functional relationships between these proteins are unclear.
18F-fluorodeoxyglucose positron emission tomography is useful for the diagnosis of intraocular sarcoidosis in patients with a normal CT scan
Authors: Chauvelot Pierre , Skanjeti Andrea , Jamilloux Yvan , de Parisot Audrey , Broussolle Christiane , Denis Philippe , Ramackers Jean Marie , Giammarile Francesco , Kodjikian Laurent , Seve Pascal
Published: January 2019

Aim

To assess the usefulness of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) and the predictive factors for the diagnosis of sarcoidosis in patients with uveitis who have normal thoracic tomography.

Methods

We retrospectively reviewed 67 consecutive patients with uveitis of unknown aetiology or a suspected sarcoidosis. All patients with normal thoracic tomography underwent an 18F-FDG PET/CT, which was blindly reinterpreted. We then assessed the proportion of positive 18F-FDG PET/CT and the impact on the final aetiology, using Abad’s criteria for the diagnosis of intraocular sarcoidosis.

Results

19 of the 67 patients (28.4%) had mediastinal hypermetabolic foci on their 18F-FDG PET/CT consistent with sarcoidosis. It identified a biopsy site in two cases, which were consistent with sarcoidosis. At the end of the study, six patients (10%) had a proven sarcoidosis, six patients (9%) were considered as having a presumed sarcoidosis and 18 patients (26.9%) as having indeterminate sarcoidosis. 18F-FDG PET/CT enabled the diagnosis of presumed sarcoidosis in these six patients. An older age at diagnosis (p=0.004) and the presence of synechiae (p=0.02) were significantly related to an abnormal 18F-FDG PET/CT, with a trend for an elevated ACE (p=0.0993). We established a nomogram to estimate the probability of having positive findings on the 18F-FDG PET/CT according to different predictive factors.

Conclusion

18F-FDG PET/CT enabled the diagnosis of intraocular sarcoidosis even in patients with a normal CT scan. Older age at diagnosis, presence of synechiae and elevated ACE are associated with positive findings on 18F-FDG PET/CT consistent with sarcoidosis.
Realist evaluation of the role of the Universal Health Coverage Partnership in strengthening policy dialogue for health planning and financing: a protocol
Authors: Robert Emilie , Ridde Valery , Rajan Dheepa , Sam Omar , Dravé Mamadou , Porignon Denis
Published: January 2019

Introduction

In 2011, WHO, the European Union and Luxembourg entered into a collaborative agreement to support policy dialogue for health planning and financing; these were acknowledged as core areas in need of targeted support in countries’ quest towards universal health coverage (UHC). Entitled ‘Universal Health Coverage Partnership’, this intervention is intended to strengthen countries’ capacity to develop, negotiate, implement, monitor and evaluate robust and integrated national health policies oriented towards UHC. It is a complex intervention involving a multitude of actors working on a significant number of remarkably diverse activities in different countries.

Methods and analysis

The researchers will conduct a realist evaluation to answer the following question: How, in what contexts, and triggering what mechanisms, does the Partnership support policy dialogue for health planning and financing towards UHC? A qualitative multiple case study will be undertaken in Togo, Liberia, Democratic Republic of Congo, Cape Verde, Burkina Faso and Niger. Three steps will be implemented: (1) formulating context–mechanism–outcome explanatory propositions to guide data collection, based on expert knowledge and theoretical literature; (2) collecting empirical data through semistructured interviews with key informants and observations of key events, and analysing data; (3) specifying the intervention theory.

Ethics and dissemination

The primary target audiences are WHO and its partner countries; international and national stakeholders involved in or supporting policy dialogues in the health sector, especially in low-income countries; and researchers with interest in UHC, policy dialogue, evaluation research and/or realist evaluation.
Cross-sectional study on medicinal products without commercial interest (MPWCI) in the Spanish market
Authors: Esteve Sala Emili , Montes Barroso Fátima , Bel Prieto Elvira , Suñé Negre Josep María
Published: January 2019

Objective

To confirm that there is a defined group of products to be protected in the Spanish therapeutic arsenal known as ‘medicinal products without commercial interest’ (MPWCI) and propose the adoption of legal measures aimed at avoiding, or reducing, the lack of supply of said products.

Design

A cross-sectional study of proposed MPWCI based on a survey. The Spanish Agency of Medicines and Medical Devices (AEMPS) was asked for a list of presentations of medicines in order to identify those whose lack could have an impact on welfare.

Setting

A search on the AEMPS website and a survey conducted among 44 companies belonging to Farmaindustria has allowed for the development of a proposal list of presentations that should continue to be marketed in Spain.

Results

Products proposed as MPWCI are old (50% of them have an authorisation of more than 50 years) and are developed by active substances of chemical origin, parenterally administered much more frequently than the rest of the general market (44%vs6.6%, respectively). Unlike oral forms, injectable forms require adequate manufacturing facilities to guarantee the quality and sterility of the product, which naturally increases the cost of the product whose price is low or obsolete. The company experts have not valued the current price revisions as a sufficient enough mechanism to change the consideration of these medicines with respect to the interest on the part of some Marketing Authorisation Holders to maintain their commercialisation.

Conclusions

As shown in the results, an upward revision of prices is necessary to contribute to the permanence of these presentations in the market, although some experts do not consider the current price revisions satisfactory enough to maintain these presentations in the market. Therefore, a specific regulation seems necessary to ensure the continuity on the market of these proposed products.
Forecasting and predicting intussusception in children younger than 48 months in Suzhou using a seasonal autoregressive integrated moving average model
Authors: Guo Wan-liang , Geng Jia , Zhan Yang , Tan Ya-lan , Hu Zhang-chun , Pan Peng , Sheng Mao , Wang Jian , Huang Shun-gen
Published: January 2019

Objective

The aims of this study were to highlight some epidemiological aspects of intussusception cases younger than 48 months and to develop a forecasting model for the occurrence of intussusception in children younger than 48 months in Suzhou.

Design

A retrospective study of intussusception cases that occurred between January 2007 and December 2017.

Setting

Retrospective chart reviews of intussusception paediatric patients in a large Children’s hospital in South-East China were performed.

Participants

The hospital records of 13 887 intussusception cases in patients younger than 48 months were included in this study.

Interventions

The modelling process was conducted using the appropriate module in SPSS V.23.0.

Methods

The Box-Jenkins approach was used to fit a seasonal autoregressive integrated moving average (ARIMA) model to the monthly recorded intussusception cases in patients younger than 48 months in Suzhou from 2007 to 2016.

Results

Epidemiological analysis revealed that intussusception younger than 48 months was reported continuously throughout the year, with peaks in the late spring and early summer months. The most affected age group was younger than 36 months. The time-series analysis showed that an ARIMA (1,0,1 1,1,1)12model offered the best fit for surveillance data of intussusception younger than 48 months. This model was used to predict intussusception younger than 48 months for the year 2017, and the fitted data showed considerable agreement with the actual data.

Conclusion

ARIMA models are useful for monitoring intussusception in patients younger than 48 months and provide an estimate of the variability to be expected in future cases in Suzhou. The models are helpful for predicting intussusception cases in Suzhou and could be useful for developing early warning systems. They may also play a key role in early detection, timely treatment and prevention of serious complications in cases of intussusception.
Depressive symptoms in people with vision impairment: a cross-sectional study to identify who is most at risk
Authors: Nollett Claire , Ryan Barbara , Bray Nathan , Bunce Catey , Casten Robin , Edwards Rhiannon Tudor , Gillespie David , Smith Daniel J , Stanford Miles , Margrain Tom H
Published: January 2019

Objective

To identify the risk factors for significant depressive symptoms in people with visual impairment in England and Wales to provide information on who is most at risk and to whom support services could be targeted in future.

Design

A cross-sectional study using baseline data from a pragmatic randomised controlled trial.

Setting and participants

990 participants aged 18 or over attending 1 of 14 low-vision rehabilitation primary care optometry-based clinics in South Wales or two hospital clinics in London.

Outcome measure

A score of ≥6 on the Geriatric Depression Scale-15 was classed as clinically significant depressive symptoms.

Results

In a multivariable logistic regression model, significant depressive symptoms were associated with age (adjusted OR (AOR)=0.82, 95% CI: 0.66 to 0.90, p<0.001), ethnicity (AOR non-white compared with white=1.72, 95% CI: 1.05 to 2.81, p=0.031), total number of eye conditions (AOR for two vs one condition=0.98, 95% CI: 0.67 to 1.43; three or more vs one condition=0.34, 95% CI: 0.15 to 0.75, p=0.026), self-reported health (AOR for excellent vs poor=0.01, 95% CI: 0.00 to 0.12; very good vs poor=0.06, 95% CI: 0.03 to 0.13; good vs poor=0.14, 95% CI: 0.08 to 0.24; fair vs poor=0.28, 95% CI: 0.18 to 0.46, p<0.001) and self-reported visual functioning (AOR=1.45, 95% CI: 1.31 to 1.61, p<0.001).

Conclusion

Younger age, a non-white ethnicity, fewer eye conditions and poorer self-reported health and visual function are risk factors for significant depressive symptoms in this population.

Trial registration number

ISRCTN46824140; Pre-results.
Experimental microdissection enables functional harmonisation of pancreatic cancer subtypes
Authors: Maurer Carlo , Holmstrom Sam R , He Jing , Laise Pasquale , Su Tao , Ahmed Aqeel , Hibshoosh Hanina , Chabot John A , Oberstein Paul E , Sepulveda Antonia R , Genkinger Jeanine M , Zhang Jiapeng , Iuga Alina C , Bansal Mukesh , Califano Andrea , Olive Kenneth P
Published: January 2019

Objective

Pancreatic ductal adenocarcinoma (PDA) has among the highest stromal fractions of any cancer and this hascomplicatedattempts at expression-based molecular classification. The goal of this work is to profile purified samples of human PDA epithelium and stroma and examine their respective contributions to gene expression in bulk PDA samples.

Design

We used laser capture microdissection (LCM) and RNA sequencing to profile the expression of 60 matched pairs of human PDA malignant epithelium and stroma samples. We then used these data to train a computational model that allowed us to infer tissue composition and generate virtual compartment-specific expression profiles from bulk gene expression cohorts.

Results

Our analysis found significant variation in the tissue composition of pancreatic tumours from different public cohorts. Computational removal of stromal gene expression resulted in the reclassification of some tumours, reconciling functional differences between different cohorts. Furthermore, we established a novel classification signature from a total of 110 purified human PDA stroma samples, finding two groups that differ in the extracellular matrix-associated and immune-associated processes. Lastly, a systematic evaluation of cross-compartment subtypes spanning four patient cohorts indicated partial dependence between epithelial and stromal molecular subtypes.

Conclusion

Our findings add clarity to the nature and number of molecular subtypes in PDA, expand our understanding of global transcriptional programmes in the stroma and harmonise the results of molecular subtyping efforts across independent cohorts.
Antibiotics-induced monodominance of a novel gut bacterial order
Authors: Hildebrand Falk , Moitinho-Silva Lucas , Blasche Sonja , Jahn Martin T , Gossmann Toni Ingolf , Huerta-Cepas Jaime , Hercog Rajna , Luetge Mechthild , Bahram Mohammad , Pryszlak Anna , Alves Renato J , Waszak Sebastian M , Zhu Ana , Ye Lumeng , Costea Paul Igor , Aalvink Steven , Belzer Clara , Forslund Sofia K , Sunagawa Shinichi , Hentschel Ute , Merten Christoph , Patil Kiran Raosaheb , Benes Vladimir , Bork Peer
Published: January 2019

Objective

The composition of the healthy human adult gut microbiome is relatively stable over prolonged periods, and representatives of the most highly abundant and prevalent species have been cultured and described. However, microbial abundances can change on perturbations, such as antibiotics intake, enabling the identification and characterisation of otherwise low abundant species.

Design

Analysing gut microbial time-series data, we used shotgun metagenomics to create strain level taxonomic and functional profiles. Community dynamics were modelled postintervention with a focus on conditionally rare taxa and previously unknown bacteria.

Results

In response to a commonly prescribed cephalosporin (ceftriaxone), we observe a strong compositional shift in one subject, in which a previously unknown species,UBorkfalki ceftriaxensis, was identified, blooming to 92% relative abundance. The genome assembly reveals that this species (1) belongs to a so far undescribed order of Firmicutes, (2) is ubiquitously present at low abundances in at least one third of adults, (3) is opportunistically growing, being ecologically similar to typical probiotic species and (4) is stably associated to healthy hosts as determined by single nucleotide variation analysis. It was the first coloniser after the antibiotic intervention that led to a long-lasting microbial community shift and likely permanent loss of nine commensals.

Conclusion

The bloom ofUB. ceftriaxensisand a subsequent one ofParabacteroides distasonisdemonstrate the existence of monodominance community states in the gut. Our study points to an undiscovered wealth of low abundant but common taxa in the human gut and calls for more highly resolved longitudinal studies, in particular on ecosystem perturbations.