bluuebunny/crossref_metadata_2025 huggingface dataset:
Skin lesions serve as clues to relapse of pediatric blastic plasmacytoid dendritic cell neoplasm
Authors: Dreyer Sean , Mednik Suzanne , Truong Allison , Worswick Scott , Scumpia Philip , Neill Daniel , Kannan Swati , Hogeling Marcia
Published: February 2018

A 10‐year‐old girl with a history of blastic plasmacytoid dendritic cell neoplasm, a rare malignancy in children, presented with recurrent skin eruptions beginning while on maintenance chemotherapy, including mildly pruritic skin‐colored plaques, tender indurated nodules, and violaceous bound‐down plaques. This case highlights an unusual presentation of relapsed blastic plasmacytoid dendritic cell neoplasm on chemotherapy, with skin lesions providing important clues to the progression of systemic disease.
Parental use of sun protection for their children—does skin color matter?
Authors: Tan Marcus G. , Nag Shudeshna , Weinstein Miriam
Published: February 2018

Background/Objectives

Excessive sun exposure during childhood is a risk factor for skin cancer. This study aimed to compare the frequency of ideal sun protection use between parents with lighter‐ and darker‐skinned children and explore their attitudes and beliefs on sun safety and their choice of sun protection.

Methods

Parents of children aged 6 months to 6 years completed self‐administered questionnaires about sun protection practices for their children. Parents assessed their child's Fitzpatrick phototype and were divided into lighter‐ (Fitzpatrick phototype I‐III) and darker‐skinned (Fitzpatrick phototype IV‐VI) groups. Sun safety guidelines from the Canadian Dermatology Association were used to qualify ideal sun protection.

Results

A total of 183 parents were included. Overall, 31 parents (17%) used ideal sun protection for their children. As their children grew older, parents were less likely to use ideal sun protection (odds ratio = 0.69, 95% confidence interval = 0.53‐0.90). Parents in the lighter‐skinned group were more likely to use ideal sun protection for their children (odds ratio = 7.4, 95% confidence interval = 2.7‐20.1), believe that sun exposure was harmful (odds ratio = 17.2, 95% confidence interval = 4.0‐74.9), and perceive value in sun protection (odds ratio = 11.4, 95% confidence interval = 3.3‐39.0); the darker‐skinned group believed that darker skin tones provided more sun protection (odds ratio = 12.4, 95% confidence interval = 6.1‐25.4).

Conclusion

Ideal parental sun protection efforts are overall low, particularly in parents of darker‐skinned children. The identified attitudes toward and beliefs about sun safety may aid in delivery of future sun protection interventions, especially in multiracial populations.
Progressive registration of image features and 3D vector lines for orientation modelling
Authors: Chang Wen‐Chi , Hung Ching‐Hui , Chen Liang‐Chien
Published: February 2018

This paper proposes a progressive method to register image features and three‐dimensional (3D) vector lines for image orientation modelling. Directed at images acquired with an approximate direct‐georeferencing capability, this study employed 3D vector lines extracted from a geographical information system (GIS) database as ground control. The major work comprises three steps: (1) straight lines were parameterised and applied as control in the collinearity condition equations to determine exterior orientation parameters (EOPs); (2) coarse registration employed quadrangle features formed from straight lines to modify the initial EOPs; and (3) a two‐step fine registration, initially involving all line‐feature candidates, followed by the selection of the most probable one from neighbouring lines. Experimental results indicate that the proposed methods can achieve an accuracy of about 2 pixels (close to the accuracy of the employed GIS database) from initial EOPs with more than 800 pixel errors. Accuracy improvements in each step of the proposed coarse‐to‐fine registration are also demonstrated.
How Social Media Facilitates Political Protest: Information, Motivation, and Social Networks
Authors: Jost John T. , Barberá Pablo , Bonneau Richard , Langer Melanie , Metzger Megan , Nagler Jonathan , Sterling Joanna , Tucker Joshua A.
Published: February 2018

It is often claimed that social media platforms such as Facebook and Twitter are profoundly shaping political participation, especially when it comes to protest behavior. Whether or not this is the case, the analysis of “Big Data” generated by social media usage offers unprecedented opportunities to observe complex, dynamic effects associated with large‐scale collective action and social movements. In this article, we summarize evidence from studies of protest movements in the United States, Spain, Turkey, and Ukraine demonstrating that: (1) Social media platforms facilitate the exchange of information that is vital to the coordination of protest activities, such as news about transportation, turnout, police presence, violence, medical services, and legal support; (2) in addition, social media platforms facilitate the exchange of emotional and motivational contents in support of and opposition to protest activity, including messages emphasizing anger, social identification, group efficacy, and concerns about fairness, justice, and deprivation as well as explicitly ideological themes; and (3) structural characteristics of online social networks, which may differ as a function of political ideology, have important implications for information exposure and the success or failure of organizational efforts. Next, we issue a brief call for future research on a topic that is understudied but fundamental to appreciating the role of social media in facilitating political participation, namely friendship. In closing, we liken the situation confronted by researchers who are harvesting vast quantities of social media data to that of systems biologists in the early days of genome sequencing.
Competing Motives in a Polarized Electorate: Political Responsiveness, Identity Defensiveness, and the Rise of Partisan Antipathy
Authors: Groenendyk Eric
Published: February 2018

According to the polarization literature, the electorate has sorted into more ideologically homogenous partisan groups, and this increase in cohesion within parties has fueled animosity between partisans. But, are mass parties really as cohesive as we think? If not, what else might be helping to drive up antipathy between partisans? Building on the dual motivations theory of party identification (Groenendyk, ), I theorize that elite polarization has amplified partisans' often competing motivations: People want to be good citizens but also good partisans. Consistent with this theory, American National Election Studies (ANES) data suggest that partisans are not just evaluating the other party more negatively, but they are also reporting less positive evaluations of, and greater ambivalence toward, their own party. This suggests substantive responsiveness. On the other hand, they appear to be rationalizing continued identification with their party in the face of this ambivalence by reporting even more negative feelings toward the other party. In other words, they seem to be engaging in the “lesser of two evils” identity defense (Groenendyk, , ). Overall, these results suggest that parties need not be internally cohesive to be divided against one another, making partisan dynamics more fluid than many accounts imply.
Polls and Elections: From the Obama Youthquake of '08 to the Trumpquake of '16: How Young People's Dislike of Hillary Clinton Cost Her the Election
Authors: Wattenberg Martin P.
Published: February 2018

Young Americans cost Hillary Clinton the presidency. Voters under the age of 30 liked Barack Obama very much in 2016, just as young people did in 2008 and 2012, but a surprising number balked at voting for Hillary Clinton to continue the Obama legacy. For such a pro‐Democratic group, the ratings that young voters gave Clinton were astoundingly low in 2016, spurred in large part by the very poor image they had of her personal character. Also surprising is that young people were not particularly put off by the extreme stands that Donald Trump took on many issues.
Atmosphere in an urban nightlife setting: A case study of the relationship between the socio‐physical context and aggressive behavior
Authors: Kalinauskaitė Indrė , Haans Antal , de Kort Yvonne A. W. , Ijsselsteijn Wijnand A.
Published: February 2018

Aggression is strongly influenced by the surrounding socio‐physical context, and the development of aggressive behavior is best understood through a continuous cycle of ongoing person‐environment interactions. Empirical studies, nevertheless, have been predominantly conducted in the laboratory, studying aggression as a short‐lived phenomenon, emerging from and within an individual, and – with situational factors studied in isolation – devoid of its context. The present field study, conducted in an urban nightlife area, complements this research. A qualitative, multi‐method approach was followed by thematic analysis to investigate ongoing behavioral patterns of the crowd vis‐à‐vis the changes in the context that co‐occurred with the development of unwanted behaviors, including aggression. In our study, we identified atmosphere as a dynamic and mood‐like, but extra‐individual state of the socio‐physical setting related to the development of aggression. Our results suggest that atmosphere affects the behavior of groups and individuals by emerging from and feeding into ongoing interactions between people and the environment. At the individual level, it appears to play its part as proximate determinant of behavior; at the crowd level it reflects the synergetic product of all those persons’ states, behaviors and interactions. Implications for aggression theory and for applications aimed at curbing aggression are discussed.
Paternal incarceration and the family: Fifteen years in review
Authors: Adams Britni L.
Published: February 2018

Since the turn of the 21st Century, research has highlighted the use of the American criminal justice system as a forager of young, low‐income, low‐educated, men of color, but less is known about how these men exist within such realities and construct meaningful relationships in their families. Research in the early 2000s has focused on how paternal incarceration affects these men, their partners, and their children. However, there is limited research about how these men understand fatherhood and the mechanisms for how paternal incarceration disrupts relationships and exacerbates inequality in the larger family system. Highlighting the consequences to family and child well‐being, the incarceration literature is beginning to focus on the variational and complicated experiences that families cope with when a father is incarcerated. This paper reviews the literature since the early 2000s, tracing what is known about incarcerated fathers and consequences for their children and families. In doing so, this paper discusses both the evolution of the literature and how more research about family processes is needed to understand the dynamic experiences of families and caregivers who manage periods of confinement during the age of mass incarceration in America.
Anticipating Negation: The Dos and Don'ts of Neg Raising
Authors: Frazier Lyn , Clifton Charles , Rich Stephanie , Duff John
Published: February 2018

Absract

A sentence like (i) can often be used interchangeably with (ii).

I don't think it's raining.

I think it's not raining.

With particular matrix predicates (e.g., think, seem, be probable) the negation from a complement clause may appear in the matrix clause, according to syntactic accounts, owing to a rule of Neg Raising, or according to semantic accounts, owing to a cancelable presupposition of the Excluded Middle (I believe p or I believe ¬p). Six written acceptability judgment studies approached the phenomena of Neg Raising (NR) as anticipation. A speaker who intends a negation may produce the negation early when the matrix verb permits the negation to be raised, especially if the polarity of the complement clause is at issue. Experiments 1 and 2, with a strict negative polarity item (NPI), showed higher ratings for sentences with Neg Raising (+NR) than for sentences without (−NR), failing to support the complexity predictions of a syntactic account where +NR involves an extra rule or dependency. Experiment 3 compared +NR predicates with −NR predicates and showed a penalty for matrix negation in the latter. Experiments 4 and 5 showed that increasing the distance between the raised negation and the negated predicate reduced the +NR advantage, but they showed that this was only an effect of increased sentence length. Experiment 6 showed an increased advantage for Neg Raising in a response to a polar question about the truth of the complement sentence. The results do not support a syntactic account but rather some version of a semantic or pragmatic account of Neg Raising coupled with the assumption that speakers anticipate salient upcoming material, such as a negative.
Digital rectal examination training among Indian medical graduates
Authors: Beena Aishwarya , Jagadisan Barath
Published: February 2018

Background

Digital rectal examination (DRE) is an important component of physical examination and an essential skill for medical graduates. DRE is often underutilised in clinical practice. The lack of confidence and expertise and also underutilization of DRE have been associated with inadequate training of medical students during their undergraduate studies. The training of Indian undergraduates in DRE has not been studied.

Methods

A questionnaire on undergraduate training in DRE was administered to students from various medical colleges joining specialty postgraduate courses in Jawaharlal Institute of Postgraduate Medical Education and Research.

Results

A total of 101 out of 131 students participated in the survey. Ninety‐one percent of students were taught DRE as undergraduates but only three‐quarters had performed DRE on patients. Among the respondents who had performed DRE, two‐thirds had performed fewer than five DREs before the completion of their medical education. Respondents who had performed fewer DREs were less confident about performing DRE (p < 0.05). Only 8% had performed DRE with manikins. Patients declining DRE and the need to minimise DRE influenced the decisions to perform DRE during training. DRE was never taught in paediatrics. DREs were most often performed only in the final year of the Bachelor of Medicine and Bachelor of Surgery (MBBS) degree, and mostly without supervision (49.3%); 61.4% were unsatisfied with their training in DRE and would like to be trained better.

A lack of confidence, expertise and use of DRE are associated with inadequate training of medical students

Conclusion

The survey indicates a lack of importance given to DRE training of undergraduate students and huge gaps in imparting this clinical skill. Training may be improved by introducing manikins, changing attitudes to DRE by incorporating it in clinical problem solving, and with more frequent opportunities to practise under supervision.
Dynamin's helical geometry does not destabilize membranes during fission
Authors: McDargh Zachary A. , Deserno Markus
Published: February 2018

It is now widely accepted that dynamin‐mediated fission is a fundamentally mechanical process: dynamin undergoes a GTP‐dependent conformational change, constricting the neck between two compartments, somehow inducing their fission. However, the exact connection between dynamin's conformational change and the scission of the neck is still unclear. In this paper, we re‐evaluate the suggestion that a change in the pitch or radius of dynamin's helical geometry drives the lipid bilayer through a mechanical instability, similar to a well‐known phenomenon occurring in soap films. We find that, contrary to previous claims, there is no such instability. This lends credence to an alternative model, in which dynamin drives the membrane up an energy barrier, allowing thermal fluctuations to take it into the hemifission state.
Localising sovereign debt: The rise of local currency bond markets in sub‐Saharan Africa
Authors: Dafe Florence , Essers Dennis , Volz Ulrich
Published: February 2018

This paper analyses the development of local currency sovereign bond markets (LCBMs) in sub‐Saharan Africa (SSA), a potentially important source of longer‐term public finance. We make two contributions to the literature. First, we build a novel data set comprising 28 SSA countries for the period 2000–14 to uncover the main correlates of LCBM capitalisation, of local currency bond (LCB) tenors and of LCB issue yields. We find that LCBM capitalisation in SSA relates to politico‐institutional factors, overall financial development and financial system structure. For LCB tenors and issue yields, inflation levels matter too. Second, we complement our econometric analysis with qualitative case studies of Kenya and Nigeria, where we further investigate the drivers of LCBM development and place LCBMs in a broader public debt context. While we document the increasing importance of LCBMs in SSA, we also highlight new vulnerabilities, including those related to investor base composition.
Passive acoustic tracking using a library of nearby sources of opportunity
Authors: Verlinden Christopher M. A. , Sarkar J. , Hodgkiss W. S. , Kuperman W. A. , Sabra K. G.
Published: February 2018

A method of localizing unknown acoustic sources using data derived replicas from ships of opportunity has been reported previously by Verlinden, Sarkar, Hodgkiss, Kuperman, and Sabra [J. Acoust. Soc. Am, 138(1), EL54–EL59 (2015)]. The method is similar to traditional matched field processing, but differs in that data-derived measured replicas are used in place of modeled replicas and, in order to account for differing source spectra between library and target vessels, cross-correlation functions are compared instead of comparing acoustic signals directly. The method is capable of localizing sources in positions where data derived replicas are available, such as locations previously transited by ships tracked using the Automatic Identification System, but is limited by the sparsity of ships of opportunity. This paper presents an extension of this localization method to regions where data derived replicas are not available by extrapolating the measured cross-correlation function replicas onto a larger search grid using waveguide invariant theory. This new augmentation provides a method for continuous tracking.
Informational masking of speech by time-varying competitors: Effects of frequency region and number of interfering formants
Authors: Roberts Brian , Summers Robert J.
Published: February 2018

This study explored the extent to which informational masking of speech depends on the frequency region and number of extraneous formants in an interferer. Target formants—monotonized three-formant (F1+F2+F3) analogues of natural sentences—were presented monaurally, with target ear assigned randomly on each trial. Interferers were presented contralaterally. In experiment 1, single-formant interferers were created using the time-reversed F2 frequency contour and constant amplitude, root-mean-square (RMS)-matched to F2. Interferer center frequency was matched to that of F1, F2, or F3, while maintaining the extent of formant-frequency variation (depth) on a log scale. Adding an interferer lowered intelligibility; the effect of frequency region was small and broadly tuned around F2. In experiment 2, interferers comprised either one formant (F1, the most intense) or all three, created using the time-reversed frequency contours of the corresponding targets and RMS-matched constant amplitudes. Interferer formant-frequency variation was scaled to 0%, 50%, or 100% of the original depth. Increasing the depth of formant-frequency variation and number of formants in the interferer had independent and additive effects. These findings suggest that the impact on intelligibility depends primarily on the overall extent of frequency variation in each interfering formant (up to ∼100% depth) and the number of extraneous formants.
Auditory enhancement under simultaneous masking in normal-hearing and hearing-impaired listeners
Authors: Kreft Heather A. , Wojtczak Magdalena , Oxenham Andrew J.
Published: February 2018

Auditory enhancement, where a target sound within a masker is rendered more audible by the prior presentation of the masker alone, may play an important role in auditory perception under variable everyday acoustic conditions. Cochlear hearing loss may reduce enhancement effects, potentially contributing to the difficulties experienced by hearing-impaired (HI) individuals in noisy and reverberant environments. However, it remains unknown whether, and by how much, enhancement under simultaneous masking is reduced in HI listeners. Enhancement of a pure tone under simultaneous masking with a multi-tone masker was measured in HI listeners and age-matched normal-hearing (NH) listeners as function of the spectral notch width of the masker, using stimuli at equal sensation levels as well as at equal sound pressure levels, but with the stimuli presented in noise to the NH listeners to maintain the equal sensation level between listener groups. The results showed that HI listeners exhibited some enhancement in all conditions. However, even when conditions were made as comparable as possible, in terms of effective spectral notch width and presentation level, the enhancement effect in HI listeners under simultaneous masking was reduced relative to that observed in NH listeners.
Hippocampal ripples down-regulate synapses
Authors: Norimoto Hiroaki , Makino Kenichi , Gao Mengxuan , Shikano Yu , Okamoto Kazuki , Ishikawa Tomoe , Sasaki Takuya , Hioki Hiroyuki , Fujisawa Shigeyoshi , Ikegaya Yuji
Published: February 2018

Rebalancing mechanisms during sleep

Synapses are often strengthened during wake periods and thus need to be homeostatically readjusted during sleep. During slow-wave sleep, synaptic depression is dominant. Sharp wave and ripple events are transient high-frequency field oscillations that occur spontaneously during slow-wave sleep in the brain. Norimoto
et al.
found that these events induced long-term depression of hippocampal synapses and may thus help to refine recently acquired memories (see the Perspective by Draguhn).

Science
, this issue p.
1524
; see also p.
1461
Topological insulator laser: Experiments
Authors: Bandres Miguel A. , Wittek Steffen , Harari Gal , Parto Midya , Ren Jinhan , Segev Mordechai , Christodoulides Demetrios N. , Khajavikhan Mercedeh
Published: February 2018

Topological protection for lasers

Ideas based on topology, initially developed in mathematics to describe the properties of geometric space under deformations, are now finding application in materials, electronics, and optics. The main driver is topological protection, a property that provides stability to a system even in the presence of defects. Harari
et al.
outline a theoretical proposal that carries such ideas over to geometrically designed laser cavities. The lasing mode is confined to the topological edge state of the cavity structure. Bandres
et al.
implemented those ideas to fabricate a topological insulator laser with an array of ring resonators. The results demonstrate a powerful platform for developing new laser systems.

Science
, this issue p.
eaar4003
, p.
eaar4005
Educated natural killer cells show dynamic movement of the activating receptor NKp46 and confinement of the inhibitory receptor Ly49A
Authors: Staaf Elina , Hedde Per Niklas , Bagawath Singh Sunitha , Piguet Joachim , Gratton Enrico , Johansson Sofia
Published: February 2018

Dynamic movements of activating and inhibitory receptors distinguish educated natural killer cells from hyporesponsive cells.
The unfolded protein response regulator ATF6 promotes mesodermal differentiation
Authors: Kroeger Heike , Grimsey Neil , Paxman Ryan , Chiang Wei-Chieh , Plate Lars , Jones Ying , Shaw Peter X. , Trejo JoAnn , Tsang Stephen H. , Powers Evan , Kelly Jeffery W. , Wiseman R. Luke , Lin Jonathan H.
Published: February 2018

The proteostasis stress-response protein ATF6 directs the mesodermal lineage during vertebrate embryogenesis and early development.
Novel Zinc-Attenuating Compounds as Potent Broad-Spectrum Antifungal Agents with
In Vitro
and
In Vivo
Efficacy
Authors: Cohrt Karen A. O'Hanlon , Marín Laura , Kjellerup Lasse , Clausen Johannes D. , Dalby-Brown William , Calera José Antonio , Winther Anne-Marie Lund
Published: February 2018

An increase in the incidence of rare but hard-to-treat invasive fungal pathogens as well as resistance to the currently available antifungal drugs calls for new broad-spectrum antifungals with a novel mechanism of action. Here we report the identification and characterization of two novel zinc-attenuating compounds, ZAC307 and ZAC989, which exhibit broad-spectrum
in vitro
antifungal activity and
in vivo
efficacy in a fungal kidney burden candidiasis model. The compounds were identified serendipitously as part of a drug discovery process aimed at finding novel inhibitors of the fungal plasma membrane proton ATPase Pma1. Based on their structure, we hypothesized that they might act as zinc chelators. Indeed, both fluorescence-based affinity determination and potentiometric assays revealed these compounds, subsequently termed zinc-attenuating compounds (ZACs), to have strong affinity for zinc, and their growth inhibitory effects on
Candida albicans
and
Aspergillus fumigatus
could be inactivated by the addition of exogenous zinc to fungal growth media. We determined the ZACs to be fungistatic, with a low propensity for resistance development. Gene expression analysis suggested that the ZACs interfere negatively with the expression of genes encoding the major components of the
A. fumigatus
zinc uptake system, thus supporting perturbance of zinc homeostasis as the likely mode of action. With demonstrated
in vitro
and
in vivo
antifungal activity, low propensity for resistance development, and a novel mode of action, the ZACs represent a promising new class of antifungal compounds, and their advancement in a drug development program is therefore warranted.
Pharmacokinetics of 2,000 Milligram Ertapenem in Tuberculosis Patients
Authors: Zuur M. A. , Ghimire S. , Bolhuis M. S. , Wessels A. M. A. , van Altena R. , de Lange W. C. M. , Kosterink J. G. W. , Touw D. J. , van der Werf T. S. , Akkerman O. W. , Alffenaar J. W. C.
Published: February 2018

Ertapenem is a carbapenem antibiotic with activity against
Mycobacterium tuberculosis
. Dose simulations in a hollow-fiber infection model showed that 2,000 mg once daily is an appropriate dose to be tested in clinical studies. Before using this dose in a phase II study, the aim of this prospective pharmacokinetic study was to confirm the pharmacokinetics of 2,000 mg once daily in tuberculosis (TB) patients. Twelve TB patients received a single intravenous dose of 2,000 mg ertapenem as a 30-min infusion. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 8, 12, and 24 h postadministration. Drug concentrations were measured using a validated liquid chromatography-tandem mass spectrometry assay. A large interindividual variation in the pharmacokinetics of ertapenem was observed. The median (interquartile range) area under the plasma concentration-time curve to infinity (AUC
0–∞
) was 2,032 (1,751 to 2,346) mg · h/liter, the intercompartmental clearance (CL
12
) was 1.941 (0.979 to 2.817) liters/h, and the volume of distribution in the central compartment (
V
1
) was 1.514 (1.064 to 2.210) liters. A more than dose-proportional increase in AUC was observed compared to results reported for 1,000 mg ertapenem in multidrug-resistant TB patients. Based on a MIC of 1.0 mg/liter, 11 out of 12 patients would have reached the target value of unbound drug exceeding the MIC over 40% of the time (
f
40%
T
>MIC). In conclusion, this study shows that 2,000 mg ertapenem once daily in TB patients reached the expected
f
40%
T
>MIC for most of the patients, and exploration in a phase 2 study can be advocated.
Assembly of Synthetic Functional Cellulosomal Structures onto the Cell Surface of Lactobacillus plantarum, a Potent Member of the Gut Microbiome
Authors: Stern Johanna , Moraïs Sarah , Ben-David Yonit , Salama Rachel , Shamshoum Melina , Lamed Raphael , Shoham Yuval , Bayer Edward A. , Mizrahi Itzhak
Published: February 2018

Heterologous display of enzymes on microbial cell surfaces is an extremely desirable approach, since it enables the engineered microbe to interact directly with the plant wall extracellular polysaccharide matrix. In recent years, attempts have been made to endow noncellulolytic microbes with genetically engineered cellulolytic capabilities for improved hydrolysis of lignocellulosic biomass and for advanced probiotics. Thus far, however, owing to the hurdles encountered in secreting and assembling large, intricate complexes on the bacterial cell wall, only free cellulases or relatively simple cellulosome assemblies have been introduced into live bacteria. Here, we employed the “adaptor scaffoldin” strategy to compensate for the low levels of protein displayed on the bacterial cell surface. That strategy mimics natural elaborated cellulosome architectures, thus exploiting the exponential features of their Lego-like combinatorics. Using this approach, we produced several bacterial consortia of
Lactobacillus plantarum
, a potent gut microbe which provides a very robust genetic framework for lignocellulosic degradation. We successfully engineered surface display of large, fully active self-assembling cellulosomal complexes containing an unprecedented number of catalytic subunits all produced
in vivo
by the cell consortia. Our results demonstrate that the enzyme stability and performance of the cellulosomal machinery, which are superior to those seen with the equivalent secreted free enzyme system, and the high cellulase-to-xylanase ratios proved beneficial for efficient degradation of wheat straw.

IMPORTANCE
The multiple benefits of lactic acid bacteria are well established in health and industry. Here we present an approach designed to extensively increase the cell surface display of proteins via successive assembly of interactive components. Our findings present a stepping stone toward proficient engineering of
Lactobacillus plantarum
, a widespread, environmentally important bacterium and potent microbiome member, for improved degradation of lignocellulosic biomass and advanced probiotics.
Enhancing the Adaptability of the Deep-Sea Bacterium Shewanella piezotolerans WP3 to High Pressure and Low Temperature by Experimental Evolution under H
2
O
2
Stress
Authors: Xie Zhe , Jian Huahua , Jin Zheng , Xiao Xiang
Published: February 2018

Oxidative stresses commonly exist in natural environments, and microbes have developed a variety of defensive systems to counteract such events. Although increasing evidence has shown that high hydrostatic pressure (HHP) and low temperature (LT) induce antioxidant defense responses in cells, there is no direct evidence to prove the connection between antioxidant defense mechanisms and the adaptation of bacteria to HHP and LT. In this study, using the wild-type (WT) strain of a deep-sea bacterium,
Shewanella piezotolerans
WP3, as an ancestor, we obtained a mutant, OE100, with an enhanced antioxidant defense capacity by experimental evolution under H
2
O
2
stress. Notably, OE100 exhibited better tolerance not only to H
2
O
2
stress but also to HHP and LT (20 MPa and 4°C, respectively). Whole-genome sequencing identified a deletion mutation in the
oxyR
gene, which encodes the transcription factor that controls the oxidative stress response. Comparative transcriptome analysis showed that the genes associated with oxidative stress defense, anaerobic respiration, DNA repair, and the synthesis of flagella and bacteriophage were differentially expressed in OE100 compared with the WT at 20 MPa and 4°C. Genetic analysis of
oxyR
and
ccpA2
indicated that the OxyR-regulated cytochrome
c
peroxidase CcpA2 significantly contributed to the adaptation of WP3 to HHP and LT. Taken together, these results confirmed the inherent relationship between antioxidant defense mechanisms and the adaptation of a benthic microorganism to HHP and LT.

IMPORTANCE
Oxidative stress exists in various niches, including the deep-sea ecosystem, which is an extreme environment with conditions of HHP and predominantly LT. Although previous studies have shown that HHP and LT induce antioxidant defense responses in cells, direct evidence to prove the connection between antioxidant defense mechanisms and the adaptation of bacteria to HHP and LT is lacking. In this work, using the deep-sea bacterium
Shewanella piezotolerans
WP3 as a model, we proved that enhancement of the adaptability of WP3 to HHP and LT can benefit from its antioxidant defense mechanism, which provided useful insight into the ecological roles of antioxidant genes in a benthic microorganism and contributed to an improved understanding of microbial adaptation strategies in deep-sea environments.
Versatile Cas9-Driven Subpopulation Selection Toolbox for Lactococcus lactis
Authors: van der Els Simon , James Jennelle K. , Kleerebezem Michiel , Bron Peter A.
Published: February 2018

CRISPR-Cas9 technology has been exploited for the removal or replacement of genetic elements in a wide range of prokaryotes and eukaryotes. Here, we describe the extension of the Cas9 application toolbox to the industrially important dairy species
Lactococcus lactis
. The Cas9 expression vector pLABTarget, encoding the
Streptocccus pyogenes
Cas9 under the control of a constitutive promoter, was constructed, allowing plug and play introduction of short guide RNA (sgRNA) sequences to target specific genetic loci. Introduction of a
pepN
-targeting derivative of pLABTarget into
L. lactis
strain MG1363 led to a strong reduction in the number of transformants obtained, which did not occur in a
pepN
deletion derivative of the same strain, demonstrating the specificity and lethality of the Cas9-mediated double-strand breaks in the lactococcal chromosome. Moreover, the same pLABTarget derivative allowed the selection of a
pepN
deletion subpopulation from its corresponding single-crossover plasmid integrant precursor, accelerating the construction and selection of gene-specific deletion derivatives in
L. lactis
. Finally, pLABTarget, which contained sgRNAs designed to target mobile genetic elements, allowed the effective curing of plasmids, prophages, and integrative conjugative elements (ICEs). These results establish that pLABTarget enables the effective exploitation of Cas9 targeting in
L. lactis
, while the broad-host-range vector used suggests that this toolbox could readily be expanded to other Gram-positive bacteria.

IMPORTANCE
Mobile genetic elements in
Lactococcus lactis
and other lactic acid bacteria (LAB) play an important role in dairy fermentation, having both positive and detrimental effects during the production of fermented dairy products. The pLABTarget vector offers an efficient cloning platform for Cas9 application in lactic acid bacteria. Targeting Cas9 toward mobile genetic elements enabled their effective curing, which is of particular interest in the context of potentially problematic prophages present in a strain. Moreover, Cas9 targeting of other mobile genetic elements enables the deciphering of their contribution to dairy fermentation processes and further establishment of their importance for product characteristics.
Fetal and Maternal Innate Immunity Receptors Have Opposing Effects on the Severity of Experimental Malaria in Pregnancy: Beneficial Roles for Fetus-Derived Toll-Like Receptor 4 and Type I Interferon Receptor 1
Authors: Rodrigues-Duarte Lurdes , Pandya Yash , Neres Rita , Penha-Gonçalves Carlos
Published: February 2018

Malaria in pregnancy (MiP) is a distinctive clinical form ofPlasmodiuminfection and is a cause of placental insufficiency leading to poor pregnancy outcomes. Maternal innate immunity responses play a decisive role in the development of placental inflammation, but the action of fetus-derived factors in MiP outcomes has been overlooked. We investigated the role of theTlr4andIfnar1genes, taking advantage of heterogenic mating strategies to dissect the effects mediated by maternally and fetally derived Toll-like receptor 4 (TLR4) or type I interferon receptor 1 (IFNAR1). Using a mouse infection system displaying severe MiP outcomes, we found that the expressions of TLR4 and IFNAR1 in the maternal compartment take part in deleterious MiP outcomes, but their fetal counterparts patently counteract these effects. We uncovered that fetal TLR4 contributes to thein vitrouptake of infected erythrocytes by trophoblasts and to the innate immune response in the placenta, offering robust protection of fetus viability, but had no sensible impact on the placental parasite burden. In contrast, we observed that the expression of IFNAR1 in the fetal compartment was associated with a reduced placental parasite burden but had little beneficial effect on fetus outcomes. Furthermore, the downregulation ofIfnar1expression in infected placentas and in trophoblasts exposed to infected erythrocytes indicated that the interferon-IFNAR1 pathway is involved in the trophoblast response to infection. This work unravels that maternal and fetal counterparts of innate immune pathways drive opposing responses in murine placental malaria and implicates the activation of innate receptors in fetal trophoblast cells in the control of placental infection and in the protection of the fetus.
Staphylococcal Protein A Contributes to Persistent Colonization of Mice with Staphylococcus aureus
Authors: Sun Yan , Emolo Carla , Holtfreter Silva , Wiles Siouxsie , Kreiswirth Barry , Missiakas Dominique , Schneewind Olaf
Published: February 2018

Staphylococcus aureuspersistently colonizes the nasopharynx in humans, which increases the risk for invasive diseases, such as skin infection and bacteremia. Nasal colonization triggers IgG responses against staphylococcal surface antigens; however, these antibodies cannot prevent subsequent colonization or disease. Here, we describeS. aureusWU1, a multilocus sequence type 88 (ST88) isolate that persistently colonizes the nasopharynx in mice. We report that staphylococcal protein A (SpA) is required for persistence ofS. aureusWU1 in the nasopharynx. Compared to animals colonized by wild-typeS. aureus, mice colonized with the Δspavariant mount increased IgG responses against staphylococcal colonization determinants. Immunization of mice with a nontoxigenic SpA variant, which cannot cross-link B cell receptors and divert antibody responses, elicits protein A-neutralizing antibodies that promote IgG responses against colonizingS. aureusand diminish pathogen persistence.

IMPORTANCEStaphylococcus aureuspersistently colonizes the nasopharynx in about one-third of the human population, thereby promoting community- and hospital-acquired infections. Antibiotics are currently used for decolonization of individuals at increased risk of infection. However, the efficacy of antibiotics is limited by recolonization and selection for drug-resistant strains. Here, we propose a model of how staphylococcal protein A (SpA), a B cell superantigen, modifies host immune responses during colonization to support continued persistence ofS. aureusin the nasopharynx. We show that this mechanism can be thwarted by vaccine-induced anti-SpA antibodies that promote IgG responses against staphylococcal antigens and diminish colonization.
Management of suspected paediatric meningitis: a multicentre prospective cohort study
Authors: Ramasamy Roshan , Willis Louise , Kadambari Seilesh , Kelly Dominic F , Heath Paul T , Nadel Simon , Pollard Andrew J , Sadarangani Manish
Published: February 2018

Objective

To quantify delays during management of children with suspected meningitis.

Design

Multicentre prospective cohort study.

Setting

Three UK tertiary paediatric centres; June 2011–June 2012

Patients

388 children aged <16 years hospitalised with suspected meningitis or undergoing lumbar puncture (LP) during sepsis evaluation.

Main outcome measures

Time of prehospital and in-hospital assessments, LP, antibiotic treatment and discharge; types of prehospital medical assessment and microbiological results. Data collected from hospital records and parental interview.

Results

220/388 (57%) children were seen by a medical professional prehospitalisation (143 by a general practitioner). Median times from initial hospital assessment to LP and antibiotic administration were 4.8 hours and 3.1 hours, respectively; 62% of children had their LP after antibiotic treatment. Median time to LP was shorter for children aged <3 months (3.0 hours) than those aged 3–23 months (6.2 hours, P<0.001) or age ≥2 years (20.3 hours, P<0.001). In meningitis of unknown cause, cerebrospinal fluid (CSF) PCR was performed for meningococcus in 7%, pneumococcus in 10% and enterovirus in 76%. When no pathogen was identified, hospital stay was longer if LP was performed after antibiotics (median 12.5 days vs 5.0 days, P=0.037).

Conclusions

Most children had LP after antibiotics were administered, reducing yield from CSF culture, and PCRs were underused despite national recommendations. These deficiencies reduce the ability to exclude bacterial meningitis, increasing unnecessary hospital stay and antibiotic treatment.
Lower limb biomechanics in femoroacetabular impingement syndrome: a systematic review and meta-analysis
Authors: King Matthew G , Lawrenson Peter R , Semciw Adam I , Middleton Kane J , Crossley Kay M
Published: February 2018

Objective

(1) Identify differences in hip and pelvic biomechanics in patients with femoroacetabular impingement syndrome (FAIS) compared with controls during everyday activities (eg, walking, squatting); and (2) evaluate the effects of interventions on hip and pelvic biomechanics during everyday activities.

Design

Systematic review.

Data sources

Medline, CINAHL, EMBASE, Scopus and SPORTDiscus until February 2017.

Methods

Primary aim: studies that investigated hip or pelvic kinematics and/or joint torques of everyday activities in patients with FAIS compared with the asymptomatic contralateral limb or a control group. Secondary aim: studies that evaluated effects of conservative or surgical interventions on patients with FAIS using pre-post or controlled clinical trial designs. Biomechanical data must have been collected using three-dimensional motion capture devices. Reporting quality was assessed using the Epidemiological Appraisal Instrument and data were pooled (standardised mean difference (SMD), 95% CI) where populations and primary outcomes were similar.

Results

Fourteen studies were included (11 cross-sectional and three pre/post intervention), varying between low and moderate reporting quality. Patients with FAIS walked with a lower: peak hip extension angle (SMD −0.40, 95% CI −0.71 to −0.09), peak internal rotation angle (−0.67, 95% CI −1.19 to −0.16) and external rotation joint torque (−0.71, 95% CI −1.07 to −0.35), and squatted to a lesser depth with no difference in hip flexion range. Pre/post intervention data were limited in number and quality, and to surgical cohorts.

Conclusion

This review suggests that patients with FAIS may demonstrate hip biomechanical impairments during walking and squatting, with minimal literature available to comment on other tasks.

Clinical relevance

The information presented in the review provides insight into the biomechanical differences associated with FAIS; however, the between-group differences were small to moderate. This information may aid in the development of management strategies for people with the condition.

PROSPEROregistration number

CRD42016038677.
Risk factors, diagnosis and non-surgical treatment for meniscal tears: evidence and recommendations: a statement paper commissioned by the Danish Society of Sports Physical Therapy (DSSF)
Authors: Thorlund Jonas Bloch , Juhl Carsten Bogh , Ingelsrud Lina Holm , Skou Søren Thorgaard
Published: February 2018

This statement aimed at summarising and appraising the available evidence for risk factors, diagnostic tools and non-surgical treatments for patients with meniscal tears. We systematically searched electronic databases using a pragmatic search strategy approach. Included studies were synthesised quantitatively or qualitatively, as appropriate. Strength of evidence was determined according to the Grading of Recommendations Assessment Development and Evaluation framework. Low-quality evidence suggested that overweight (degenerative tears, k=3), male sex (k=4), contact and pivoting sports (k=2), and frequent occupational kneeling/squatting (k=3) were risk factors for meniscal tears. There was low to moderate quality evidence for low to high positive and negative predictive values, depending on the underlying prevalence of meniscal tears for four common diagnostic tests (k=15, n=2474). Seven trials investigated exercise versus surgery (k=2) or the effect of surgery in addition to exercise (k=5) for degenerative meniscal tears. There was moderate level of evidence for exercise improving self-reported pain (Effect Size (ES)−0.51, 95% CI −1.16 to 0.13) and function (ES −0.06, 95% CI −0.23 to 0.11) to the same extent as surgery, and improving muscle strength to a greater extent than surgery (ES −0.45, 95% CI −0.62 to −0.29). High-quality evidence showed no clinically relevant effect of surgery in addition to exercise on pain (ES 0.18, 95% 0.05 to 0.32) and function (ES, 0.13 95% CI −0.03 to 0.28) for patients with degenerative meniscal tears. No randomised trials comparing non-surgical treatments with surgery in patients younger than 40 years of age or patients with traumatic meniscal tears were identified. Diagnosis of meniscal tears is challenging as all clinical diagnostic tests have high risk of misclassification. Exercise therapy should be recommended as the treatment of choice for middle-aged and older patients with degenerative meniscal lesions. Evidence on the best treatment for young patients and patients with traumatic meniscal tears is lacking.
Methodological quality and synthesis of case series and case reports
Authors: Murad Mohammad Hassan , Sultan Shahnaz , Haffar Samir , Bazerbachi Fateh
Published: February 2018

Case reports and case series are uncontrolled study designs known for increased risk of bias but have profoundly influenced the medical literature and continue to advance our knowledge. In this guide, we present a framework for appraisal, synthesis and application of evidence derived from case reports and case series. We propose a tool to evaluate the methodological quality of case reports and case series based on the domains of selection, ascertainment, causality and reporting and provide signalling questions to aid evidence-based practitioners and systematic reviewers in their assessment. We suggest using evidence derived from case reports and case series to inform decision-making when no other higher level of evidence is available.
Comparative evaluation of a novel solar powered low-cost ophthalmoscope (Arclight) by eye healthcare workers in Malawi
Authors: Blundell Rebecca , Roberts David , Fioratou Evridiki , Abraham Carl , Msosa Joseph , Chirambo Tamara , Blaikie Andrew
Published: February 2018

This study compared a novel low-cost solar powered direct ophthalmoscope called the Arclight with a traditional direct ophthalmoscope (TDO). After appropriate training, 25 Malawian eye healthcare workers were asked to examine 12 retinal images placed in a teaching manikin head with both the Arclight ophthalmoscope and a traditional direct ophthalmoscope (Keeler Professional V.2.8). Participants were scored on their ability to identify clinical signs, to make a diagnosis and how long they took to make a diagnosis. They were also asked to score each ophthalmoscope for ‘ease of use’. Statistically significant differences were found in favour of the Arclight in the number of clinical signs identified, correct diagnoses made and ease of use. The ophthalmoscopes were equally effective as a screening tool for diabetic retinopathy, and there was no statistically difference in time to diagnosis. The authors conclude that the Arclight offers an easy to use, low cost alternative to the traditional direct ophthalmoscope to meet the demands for screening and diagnosis of visually impairing eye disorders in low-income and middle-income countries.