bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dust spectrum and polarisation at 850 μm in the massive IRDC G035.39-00.33
Authors: Juvela Mika , Guillet Vincent , Liu Tie , Ristorcelli Isabelle , Pelkonen Veli-Matti , Alina Dana , Bronfman Leonardo , Eden David J. , Kim Kee Tae , Koch Patrick M. , Kwon Woojin , Lee Chang Won , Malinen Johanna , Micelotta Elisabetta , Montillaud Julien , Rawlings Mark G. , Sanhueza Patricio , Soam Archana , Traficante Alessio , Ysard Nathalie , Zhang Chuan-Peng 
Published: September 2018

Context. The sub-millimetre polarisation of dust emission from star-forming clouds carries information on grain properties and on the effects that magnetic fields have on cloud evolution.
Aims. Using observations of a dense filamentary cloud G035.39-00.33, we aim to characterise the dust emission properties and the variations of the polarisation fraction.
Methods. JCMT SCUBA-2/POL-2 observations at 850 μm were combined with Planck 850 μm(353 GHz) data to map polarisation fraction at small and large scales. With previous total intensity SCUBA-2 observations (450 and 850 μm) and Herschel data, the column densities were determined via modified black-body fits and via radiative transfer modelling. Models were constructed to examine how the observed polarisation angles and fractions depend on potential magnetic field geometries and grain alignment processes.
Results. POL-2 data show clear changes in the magnetic field orientation. These are not in contradiction with the uniform orientation and almost constant polarisation fraction seen by Planck, because of the difference in the beam sizes and the POL-2 data being affected by spatial filtering. The filament has a peak column density of N(H2) ~ 7 × 1022 cm−2, a minimum dust temperature of T ~ 12 K, and a mass of ~4300 M⊙ for the area N(H2) > 5 × 1021 cm−2. The estimated average value of the dust opacity spectral index is β ~ 1.9. The ratio of sub-millimetre and J-band optical depths is τ (250 μm)∕τ (J) ~ 2.5 × 10−3, more than four times the typical values for diffuse medium. The polarisation fraction decreases as a function of column density to p ~ 1% in the central filament. Because of noise, the observed decrease of p(N) is significant only at N(H2) > 2 × 1022 cm−2. The observations suggest that the grain alignment is not constant. Although the data can be explained with a complete loss of alignment at densities above ~104 cm−3 or using the predictions of radiative torques alignment, the uncertainty of the field geometry and the spatial filtering of the SCUBA-2 data prevent strong conclusions.
Conclusions. The G035.39-00.33 filament shows strong signs of dust evolution and the low polarisation fraction is suggestive of a loss of polarised emission from its densest parts.
Day-to-Day Home Blood Pressure Variability and Orthostatic Hypotension: The Nagahama Study
Authors: Tabara Yasuharu , Matsumoto Takeshi , Murase Kimihiko , Setoh Kazuya , Kawaguchi Takahisa , Nagashima Shunsuke , Kosugi Shinji , Nakayama Takeo , Wakamura Tomoko , Hirai Toyohiro , Chin Kazuo , Matsuda Fumihiko ,   Nagahama study group
Published: September 2018

Abstract

BACKGROUND
The aim of this study is to clarify associations between orthostatic blood pressure (BP) change, as well as possible physiological factors, and day-to-day home BP variability, a promising risk factor for cardiovascular outcomes.

METHODS
Study participants were 6,465 community residents (age 58.3 years). Home BP was measured every morning and evening for 7 days. Orthostatic BP was calculated as the maximum difference between BP measured while sitting and remeasured after 1 and 3 minutes standing.

RESULTS
Frequency of individuals who showed orthostatic BP decline was as follows: systolic BP (SBP) change ≥−20 mm Hg: 2.6%, ≥−10 mm Hg: 14.1%. These subgroups showed larger home SBP variability (average real variability: 11.3 ± 5.3, 8.7 ± 3.9 mm Hg) when compared with orthostatic normotensives (7.6 ± 3.7 mm Hg) (all P &lt; 0.001). Multiple linear regression analysis adjusted for major covariates, including seated BP, identified orthostatic BP drop as an independent determinant for morning BP variability (≥−20 mm Hg: β = 0.037, P = 0.003; ≥−10 mm Hg: β = 0.026, P = 0.036) but not for evening BP variability. Carotid hypertrophy was significantly associated with home BP variability (morning: β = 0.052, P = 0.001; evening: β = 0.065, P &lt; 0.001) and showed a U-shaped association with orthostatic BP change. Plasma B-type natriuretic peptide level, a previously suggested factor for BP variability, did not show significant association with morning and evening BP variability.

CONCLUSION
Orthostatic BP decline was significantly associated with morning BP variability. Large artery atherosclerosis was a common risk factor.
The promise, problems and pitfalls of mass drug administration for malaria elimination: a qualitative study with scientists and policymakers
Authors: Kaehler Nils , Adhikari Bipin , Cheah Phaik Yeong , Day Nicholas P J , Paris Daniel H , Tanner Marcel , Pell Christopher 
Published: September 2018

Abstract

Background
The emergence of artemisinin resistance in the Greater Mekong Subregion (GMS) has prompted urgent containment measures. One possible approach is mass drug administration (MDA). This article explores attitudes towards and perceptions of MDA for malaria elimination among policymakers and leading malariologists.

Methods
Thirty-two semistructured interviews (SSI) were conducted with policymakers (n=17) and principal investigators (n=15) selected based on their involvement in malaria prevention, control and elimination in the GMS. Interviews were audio recorded and transcribed for qualitative content (thematic) analysis using NVivo (QSR International, Doncaster, Victoria, Australia).

Results
Researchers and policymakers described reluctance and consequently delays to pilot MDA for malaria elimination. Most policymakers and some researchers reported concerns around the evidence base, citing a lack of data on its effectiveness and appropriate target populations. There were also worries about promoting resistance. Other issues included a previous lack of support from the World Health Organization, past MDAs, the remoteness of target populations and challenges explaining the rationale for MDA.

Conclusions
The complex rationale for MDA for malaria elimination, mistaking pilot studies for implementation, past experiences with MDA, difficulties in selecting appropriate sites and the WHO’s lack of clear backing undermined the support for MDA for malaria elimination.
Assessment of eHealth behaviors in national surveys: a systematic review of instruments
Authors: Hong Y Alicia , Cho Jinmyoung 
Published: September 2018

AbstractObjectivesTo conduct a systematic review of instruments used in national surveys of eHealth behaviors.Materials and MethodsMajor databases and websites of federal agencies were searched with pre-determined inclusion and exclusion criteria. National surveys with measures of eHealth behaviors were identified. The survey instruments were retrieved, and their measures of eHealth behaviors were categorized and critiqued.ResultsWe located 13 national surveys containing eHealth behavior assessment questions that were administered from 1999 to 2017. Most surveys were conducted annually or biennially and typically covered topics on searching health information, obtaining social support, communicating with healthcare providers, and buying medicine online; recent surveys included items related to personal health management and use of mobile tools. There were redundant measures of searching health information online but insufficient measures of use of mobile apps, social media, and wearable devices.DiscussionFuture assessment of eHealth behaviors should reflect the growing varieties of behaviors enabled by technology development and reflect the current mobile ownership patterns in diverse social groups. More studies also need to include longitudinal surveys, integrative and standardized measures, and better designs to allow data linkage and comparison.ConclusionThe existing survey instruments covering eHealth behaviors are rather limited compared to fast technological progress. We call for more national surveys on eHealth behaviors that are more responsive to technology development; we also advocate for more analysis and dissemination of existing national data on eHealth behaviors for evidence-based health policies.
Potential application of phage therapy for prophylactic treatment against Pseudomonasaeruginosabiofilm Infections
Authors: Gurkar Aditi , Balasubramanian Deepak , Manur Jayasheela , Mathee Kalai 
Published: September 2018

ABSTRACTThe majority of the microbial activity in humans is in the form of biofilms, i.e., an exopolysaccharide-enclosed bacterial mass. Unlike planktonic cells and the cells on the surface of the biofilm, the biofilm-embedded cells are more resistant to the effects of the antibiotics and the host cellular defense mechanisms. A combination of biofilm growth and inherent resistance prevents effective antibiotic treatment ofPseudomonas aeruginosainfections including those in patients with cystic fibrosis. Antibiotic resistance has led to an increasing interest in alternative modalities of treatment. Thus, phages that multiplyin situand in the presence of susceptible hosts can be used as natural, self-limiting, and profoundly penetrating antibacterial agents. The objective of this study is to identify active phages against a collection ofP. aeruginosaisolates (PCOR strains) including the prototype PAO1 and the isogenic constitutively alginate-producing PDO300 strains. These PCOR strains were tested against six phages (P105, P134, P140, P168, P175B, and P182). The analysis shows 69 % of the PCOR isolates are sensitive and the rest are resistant to all six phages. These phages were then tested for their ability to inhibit biofilm formation using a modified biofilm assay. The analysis demonstrated that the sensitive strains showed increased resistance, but none of the susceptible strains from the initial screening were resistant. Using the minimum biofilm eradication concentration (MBEC) assay for biofilm formation, the biofilm eradication ability of the phages was tested. The data showed that a higher volume of phage was required to eradicate preformed biofilms than the amount required to prevent colonization of planktonic cells. This data supports the idea of phage therapy more as a prophylactic treatment.
A Neurodevelopmental Disorder Caused by Mutations in the VPS51 Subunit of the GARP and EARP Complexes
Authors: Gershlick David C. , Ishida Morié , Jones Julie R. , Bellomo Allison , Bonifacino Juan S. , Everman David B. 
Published: September 2018

AbstractGARP and EARP are related heterotetrameric protein complexes that associate with the cytosolic face of thetrans-Golgi network and recycling endosomes, respectively. At these locations, GARP and EARP function to promote the fusion of endosome-derived transport carriers with their corresponding compartments. GARP and EARP share three subunits, VPS51, VPS52 and VPS53, and each has an additional complex-specific subunit, VPS54 or VPS50, respectively. The role of these complexes in human physiology, however, remains poorly understood. By exome sequencing, we have identified compound heterozygous mutations in the gene encoding the shared GARP/EARP subunit VPS51 in a six-year-old patient with severe global developmental delay, microcephaly, hypotonia, epilepsy, cortical vision impairment, pontocerebellar abnormalities, failure to thrive, liver dysfunction, lower extremity edema and dysmorphic features. The mutation in one allele causes a frameshift that produces a longer but highly unstable protein that is degraded by the proteasome. In contrast, the other mutant allele produces a protein with a single amino-acid substitution that is stable but assembles less efficiently with the other GARP/EARP subunits. Consequently, skin fibroblasts from the patient have reduced levels of fully-assembled GARP and EARP complexes. Likely because of this deficiency, the patient’s fibroblasts display altered distribution of the cation-independent mannose 6-phosphate receptor, which normally sorts acid hydrolases to lysosomes. Furthermore, a fraction of the patient’s fibroblasts exhibit swelling of lysosomes. These findings thus identify a novel genetic locus for a neurodevelopmental disorder and highlight the critical importance of GARP/EARP function in cellular and organismal physiology.
HLA-DQA1*05 is associated with the development of antibodies to anti-TNF therapy
Authors: Sazonovs Aleksejs , Kennedy Nick , Moutsianas Loukas , Heap Graham A. , Rice Daniel L. , Reppell Mark , Bewshea Claire , Walker Gareth , Perry Mandy H. , McDonald Timothy J. , Lees Charlie , Cummings Fraser , Parkes Miles , Mansfield John , Barrett Jeffrey C. , McGovern Dermot , Goodhand James , Anderson Carl A. , Ahmad Tariq ,   PANTS consortium
Published: September 2018

SummaryBackgroundAnti-tumour necrosis factor (anti-TNF) therapies are the most widely used biologic therapies for treating immune-mediated diseases. Their efficacy is significantly reduced by the development of anti-drug antibodies which can lead to treatment failure and adverse reactions. The biological mechanisms underlying antibody development are unknown but the ability to identify subjects at higher risk would have significant clinical benefits.MethodsThe PANTS cohort consists of Crohn’s disease patients recruited prior to first administration of anti-TNF, with serial measurements of anti-drug antibody titres. We performed a genome-wide association study across 1240 individuals from this cohort to identify genetic variants associated with anti-drug antibody development.FindingsThe Human Leukocyte Antigen allele, HLA-DQA1*05, carried by approximately 40% of Europeans, significantly increased the rate of anti-drug antibody development (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.60 to 2.25; P=5.88×10-13). This association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32 to 2.70) and infliximab (HR, 1.92; 95% CI, 1.57 to 2.33), and for patients treated with mono-(HR, 1.75; 95% CI, 1.37 to 2.22) or combination therapy with immunomodulators (HR, 2.0; 95% CI, 1.57 to 2.58).InterpretationHLA-DQA1*05 is significantly associated with an increased rate of anti-drug antibody formation in patients with Crohn’s disease treated with infliximab and adalimumab. Pre-treatment HLA-DQA1*05 genetic testing may help personalise the choice of anti-TNF therapy and allow the targeted use of immunomodulator therapy to minimise risk and maximise response.
Limited significance of the in situ proximity ligation assay
Authors: Alsemarz Azam , Lasko Paul , Fagotto François 
Published: September 2018

SummaryIn situ proximity ligation assay (isPLA) is an increasingly popular technique that aims at detecting the close proximity of two molecules in fixed samples using two primary antibodies. The maximal distance between the antibodies required for producing a signal is 40 nm, which is lower than optical resolution and approaches the macromolecular scale. Therefore, isPLA may provide refined positional information, and is commonly used as supporting evidence for direct or indirect protein-protein interaction. However, we show here that this method is inherently prone to false interpretations, yielding positive and seemingly ‘specific’ signals even for totally unrelated antigens. We discuss the difficulty to produce adequate specificity controls. We conclude that isPLA data should be considered with extreme caution.
Left mid-ventral temporal cortex interacts with early visual cortex and the anterior temporal lobe to support word individuation
Authors: Boring Matthew J. , Hirshorn Elizabeth A. , Li Yuanning , Ward Michael J. , Mark Richardson R. , Fiez Julie A. , Ghuman Avniel Singh 
Published: September 2018

AbstractThe left mid-ventral temporal cortex (lmVTC) plays a dynamic role in reading. In this study we investigated the neural interactions that influence lmVTC dynamics and the lexical information these interactions are dependent on. We monitored activity with either intracranial electroencephalography or magnetoencephalography while participants viewed real words, pseudowords, consonant strings, and false fonts. A coarse level representation in early lmVTC activity allowed for decoding of visually dissimilar real words, pseudowords, and false fonts. Functional interactions between anterior ventral temporal regions, possibly containing stored knowledge about words, and low-order visual regions occurred after this initial stage of processing and was followed by the individuation of orthographically similar real words in lmVTC, but not similar pseudowords, letter strings, or false fonts. These results suggest that the individuation of real word representations in lmVTC is catalyzed by stored knowledge about word forms that emerges from network-level interactions with anterior regions of the temporal lobe.
Hydrodynamics of the frontal strike in aquatic snakes: drag, added mass and the possible consequences for prey capture success
Authors: Segall Marion , Herrel Anthony , Godoy-Diana Ramiro 
Published: September 2018

AbstractNatural selection favors organisms that are the most successful in fitness-related behaviors such as foraging. Secondary adaptations pose the problem of re-adapting an already ‘optimized’ phenotype to new constraints. When animals forage underwater, they face strong physical constraints, particularly when capturing prey. Successful prey capture requires a predator to be fast and to generate a high acceleration. This involves two main constraints due to the surrounding fluid: drag and added mass. Both constraints are related to the shape of the animal. We experimentally explore the relationship between shape and performance in the context of an aquatic snake strike. As a model, we use two different 3D- printed snake heads representing typical shapes of aquatically-foraging and non-aquatically- foraging snakes, and frontal strike kinematics based on in vivo observations. By using direct force measurements, we compare the drag and added mass faced by the aquatic and non- aquatic snake models during a strike. Our results show that both drag and added mass are optimized in aquatic snakes. Using flow field measurements with particle image velocimetry, we examine the fluid dynamical mechanisms that could be behind the reduction of hydrodynamic constraints observed for the aquatic snake head shape, which makes it well suited to capture prey under water.Summary statementThe present work explores the functional implications of head shape 15 in a group of aquatic predators using a fluid mechanics approach.
Male-Specific Protein Disulphide Isomerase Function is Essential forPlasmodiumFertilization and Transmission
Authors: Angrisano Fiona , Sala Katarzyna A. , Tapanelli Sofia , Christophides George K. , Blagborough Andrew M. 
Published: September 2018

SummaryInhibiting transmission ofPlasmodiumis an essential strategy in malaria eradication, and the biological process of gamete fusion during fertilization is a proven target for this approach. The lack of knowledge of the mechanisms underlying fertilization have been a hindrance in the development of transmission-blocking interventions. Here we describe a protein disulphide isomerase essential for malarial transmission (PDI-Trans/PBANKA_0820300) to the mosquito. We show thatPDI-Transactivity is male-specific, surface expressed, essential for fertilization/transmission, and exhibits disulphide isomerase activity which is up-regulated post-gamete activation. We demonstrate thatPDI-Transis a viable anti-malarial drug and vaccine target blocking malarial transmission with the use of the PDI inhibitor bacitracin (98.21%/92.48% reduction in intensity/prevalence), and anti-PDI-Transpeptide antibodies (66.22%/33.16% reduction in intensity/prevalence). To our knowledge, these results provide the first primary evidence that protein disulphide isomerase function is essential for malarial transmission, and emphasize the potential of anti-PDI agents to act as anti-malarials, facilitating the future development of novel transmission-blocking compounds or vaccines.
Evolution of the highly repetitive PEVK region of titin across mammals
Authors: Muenzen Kathleen , Monroy Jenna , Finseth Findley R. 
Published: September 2018

ABSTRACTThe protein titin plays a key role in vertebrate muscle where it acts like a giant molecular spring. Despite its importance and conservation over vertebrate evolution, a lack of high quality annotations in non-model species makes comparative evolutionary studies of titin challenging. The PEVK region of titin—named for its high proportion of Pro-Glu-Val-Lys amino acids—is particularly difficult to annotate due to its abundance of alternatively spliced isoforms and short, highly repetitive exons. To understand PEVK evolution across mammals, we first developed a bioinformatics tool, PEVK_Finder, to annotate PEVK exons from genomic sequences of titin and then applied it to a diverse set of mammals. PEVK_Finder consistently outperforms standard annotation tools across a broad range of conditions and improves annotations of the PEVK region in non-model mammalian species. We find that the PEVK region can be divided into two subregions (PEVK-N, PEVK-C) with distinct patterns of evolutionary constraint and divergence. The bipartite nature of the PEVK region has implications for titin diversification. In the PEVK-N region, certain exons are conserved and may be essential, but natural selection also acts on particular codons. This region is also rich in glutamate and may contribute to actin binding. In the PEVK-C, exons are more homogenous and length variation of the PEVK region may provide the raw material for evolutionary adaptation in titin function. Taken together, we find that the very complexity that makes titin a challenge for annotation tools may also promote evolutionary adaptation.