bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do we have any hope of detecting scattering between dark energy and baryons through cosmology?
Authors: Vagnozzi Sunny , Visinelli Luca , Mena Olga , Mota David F 
Published: January 2020

ABSTRACT
We consider the possibility that dark energy and baryons might scatter off each other. The type of interaction we consider leads to a pure momentum exchange, and does not affect the background evolution of the expansion history. We parametrize this interaction in an effective way at the level of Boltzmann equations. We compute the effect of dark energy-baryon scattering on cosmological observables, focusing on the cosmic microwave background (CMB) temperature anisotropy power spectrum and the matter power spectrum. Surprisingly, we find that even huge dark energy-baryon cross-sections $\sigma _{xb} \sim {\cal O}({\rm b})$, which are generically excluded by non-cosmological probes such as collider searches or precision gravity tests, only leave an insignificant imprint on the observables considered. In the case of the CMB temperature power spectrum, the only imprint consists in a sub-per cent enhancement or depletion of power (depending whether or not the dark energy equation of state lies above or below −1) at very low multipoles, which is thus swamped by cosmic variance. These effects are explained in terms of differences in how gravitational potentials decay in the presence of a dark energy-baryon scattering, which ultimately lead to an increase or decrease in the late-time integrated Sachs–Wolfe power. Even smaller related effects are imprinted on the matter power spectrum. The imprints on the CMB are not expected to be degenerate with the effects due to altering the dark energy sound speed. We conclude that, while strongly appealing, the prospects for a direct detection of dark energy through cosmology do not seem feasible when considering realistic dark energy-baryon cross-sections. As a caveat, our results hold to linear order in perturbation theory.
A lack of evolution in the very bright end of the galaxy luminosity function from z ≃ 8 to 10
Authors: Bowler R A A , Jarvis M J , Dunlop J S , McLure R J , McLeod D J , Adams N J , Milvang-Jensen B , McCracken H J 
Published: January 2020

ABSTRACT
We utilize deep near-infrared survey data from the UltraVISTA fourth data release (DR4) and the VIDEO survey, in combination with overlapping optical and Spitzer data, to search for bright star-forming galaxies at z ≳ 7.5. Using a full photometric redshift fitting analysis applied to the ∼6 $\, {\rm deg}^2$ of imaging searched, we find 27 Lyman break galaxies (LBGs), including 20 new sources, with best-fitting photometric redshifts in the range 7.4 &lt; z &lt; 9.1. From this sample, we derive the rest-frame UV luminosity function at z = 8 and z = 9 out to extremely bright UV magnitudes (MUV ≃ −23) for the first time. We find an excess in the number density of bright galaxies in comparison to the typically assumed Schechter functional form derived from fainter samples. Combined with previous studies at lower redshift, our results show that there is little evolution in the number density of very bright (MUV ∼ −23) LBGs between z ≃ 5 and z ≃ 9. The tentative detection of an LBG with best-fitting photometric redshift of z = 10.9 ± 1.0 in our data is consistent with the derived evolution. We show that a double power-law fit with a brightening characteristic magnitude (ΔM*/Δz ≃ −0.5) and a steadily steepening bright-end slope (Δβ/Δz ≃ −0.5) provides a good description of the z &gt; 5 data over a wide range in absolute UV magnitude (−23 &lt; MUV &lt; −17). We postulate that the observed evolution can be explained by a lack of mass quenching at very high redshifts in combination with increasing dust obscuration within the first ${\sim}1 \, {\rm Gyr}$ of galaxy evolution.
A Behavior-Manipulating Virus Relative as a Source of Adaptive Genes forDrosophilaParasitoids
Authors: Di Giovanni Deborah , Lepetit David , Guinet Benjamin , Bennetot Bastien , Boulesteix Matthieu , Couté Yohann , Bouchez Olivier , Ravallec Marc , Varaldi Julien 
Published: January 2020

AbstractSome species of parasitic wasps have domesticated viral machineries to deliver immunosuppressive factors to their hosts. Up to now, all described cases fall into the Ichneumonoidea superfamily, which only represents around 10% of hymenoptera diversity, raising the question of whether such domestication occurred outside this clade. Furthermore, the biology of the ancestral donor viruses is completely unknown. Since the 1980s, we know that Drosophila parasitoids belonging to the Leptopilina genus, which diverged from the Ichneumonoidea superfamily 225 Ma, do produce immunosuppressive virus-like structure in their reproductive apparatus. However, the viral origin of these structures has been the subject of debate. In this article, we provide genomic and experimental evidence that those structures do derive from an ancestral virus endogenization event. Interestingly, its close relatives induce a behavior manipulation in present-day wasps. Thus, we conclude that virus domestication is more prevalent than previously thought and that behavior manipulation may have been instrumental in the birth of such associations.
Characterization and Biosynthesis of Lipids in Paulinella micropora MYN1: Evidence for Efficient Integration of Chromatophores into Cellular Lipid Metabolism
Authors: Sato Naoki , Yoshitomi Toru , Mori-Moriyama Natsumi 
Published: January 2020

Abstract
The chromatophores found in the cells of photosynthetic Paulinella species, once believed to be endosymbiotic cyanobacteria, are photosynthetic organelles that are distinct from chloroplasts. The chromatophore genome is similar to the genomes of α-cyanobacteria and encodes about 1,000 genes. Therefore, the chromatophore is an intriguing model of organelle formation. In this study, we analyzed the lipids of Paulinella micropora MYN1 to verify that this organism is a composite of cyanobacterial descendants and a heterotrophic protist. We detected glycolipids and phospholipids, as well as a betaine lipid diacylglyceryl-3-O-carboxyhydroxymethylcholine, previously detected in many marine algae. Cholesterol was the only sterol component detected, suggesting that the host cell is similar to animal cells. The glycolipids, presumably present in the chromatophores, contained mainly C16 fatty acids, whereas other classes of lipids, presumably present in the other compartments, were abundant in C20 and C22 polyunsaturated fatty acids. This suggests that chromatophores are metabolically distinct from the rest of the cell. Metabolic studies using isotopically labeled substrates showed that different fatty acids are synthesized in the chromatophore and the cytosol, which is consistent with the presence of both type I and type II fatty acid synthases, supposedly present in the cytosol and the chromatophore, respectively. Nevertheless, rapid labeling of the fatty acids in triacylglycerol and phosphatidylcholine by photosynthetically fixed carbon suggested that the chromatophores efficiently provide metabolites to the host. The metabolic and ultrastructural evidence suggests that chromatophores are tightly integrated into the whole cellular metabolism.
Statin use and risk of joint replacement due to osteoarthritis and rheumatoid arthritis: a propensity-score matched longitudinal cohort study
Authors: Sarmanova Aliya , Doherty Michael , Kuo Changfu , Wei Jie , Abhishek Abhishek , Mallen Christian , Zeng Chao , Wang Yilun , Lei Guanghua , Zhang Weiya 
Published: January 2020

Abstract

Objective
Statins are reported to have a potential benefit on progression of OA and on disease activity in RA, but existing evidence is conflicting. Our objective was to examine whether statins associate with reduction in the risk for joint replacement due to OA and RA.

Methods
This was a propensity score-matched cohort study. Electronic health records from the UK Clinical Practice Research Datalink were used. We selected people prescribed statins and people never prescribed statins. Each statin user was matched to a non-user by age, gender, practice and propensity score for statin prescription. The main outcome measures were knee or hip joint replacement overall, and specifically because of OA or RA. The association between statins and risk of joint replacement was assessed using Cox proportional hazard regression. Statin exposure was categorized according to the potency of reducing low-density lipoprotein as low (21–28%), medium (32–38%) or high (42–55%) intensity.

Results
A total of 178 467 statin users were matched with 178 467 non-users by age, gender, practice and propensity score. Overall, statin was not associated with reduced risk of knee or hip replacement (hazard ratio 0.99, 95% CI: 0.97, 1.03), unless prescribed at high strength (0.86, 0.75–0.98). The reduced risk was only observed for joint replacement due to RA (0.77, 0.63–0.94) but not OA (0.97, 0.94–1.01).

Conclusion
Statins at high intensity may reduce the risk of hip or knee replacement. This effect may be RA specific. Further studies to investigate mechanisms of risk reduction and the impact in people with RA are warranted.
Clinical trial data transparency and GDPR compliance: Implications for data sharing and open innovation
Authors: Minssen Timo , Rajam Neethu , Bogers Marcel 
Published: January 2020

Abstract
Recent European Union (EU) initiatives and legislation have considerably increased public access to clinical trials data (CTD). These developments are generally much welcomed for the enhancement of science, trust, and open innovation. However, they also raise many questions and concerns, not least at the interface between CTD transparency and other areas of evolving EU law on the protection of trade secrets, IPRs, and privacy. This article focuses on privacy issues and on the interrelation between developments in transparency and the EU’s new General Data Protection Regulation 2016/679 (GDPR). More specifically, this article examines: (1) the origins and rationales of EU transparency regulations, including the incidents and concerns that have shaped them; (2) the features and implications of the GDPR which are relevant in the context of clinical trials; and (3) the risk for tensions between the GDPR and the policy goals of CTD transparency, as well as implications for data sharing and open innovation. Ultimately, we elaborate on factors that should be carefully considered and addressed to reap the full benefits of CTD transparency.
Apixaban-induced leukocytoclastic vasculitis
Authors: Esbech Peter , Schmidt Jakob Nøhr , Andersen Lone Kærslund , Damkier Per 
Published: January 2020

Summary

Introduction:
Drug-induced vasculitis is a rare adverse drug reaction and the potential to induce such a reaction is often established postmarketing. Leukocytoclastic vasculitis - a subtype of drug-induced vasculitis - often presents itself with palpable purpuric lesions, and often within weeks of initial administration.

Case-description:
We present a 62-year-old male who presented with leukocytoclastic vasculitis within the first 8 days of apixaban-initiation. Symptoms improved upon discontinuation and resolved after several months of prednisone therapy.

Literature review:
We conducted a search on PubMed, which yielded 10 reports of leukocytoclastic vasculitis induced by NOACs, of these 10 only 1 had been caused by apixaban, 4 caused by dabigatran and 5 had been caused by rivaroxaban. Of these cases, one presented with leukocytoclastic vasculitis induced by both rivaroxaban and dabigatran, and one case presented successful switch from apixaban to rivaroxaban.

Conclusion:
Apixaban-induced leukocytoclastic vasculitis is a rare but serious and important adverse reaction.
The role of mature mycolic acids in mycobacterial biofilm formation and interactions with the human complement system
Authors: Halkerston Rachel , Davies Katherine , Tolley Howard , Keating Thomas , Taylor Stephen , Alderwick Luke , Bacon Joanna 
Published: January 2020

Tuberculosis, causative agent Mycobacterium tuberculosis, caused an estimated 10 million new cases and 1.6 million deaths in 2017.
Mycobacterial cell wall components are important for host-pathogen interactions and modulating the innate and adaptive immune response. Much is understood about the interplay between bacterial phenotype, cell wall modulation and interaction with aspects of the immune response. However, the impact of phenotype, such as biofilms on complement system activation, has not been studied in-depth.

M. tuberculosis may persist as biofilms in a chronic, non-replicating state. Mycolic acids are a major cell wall lipid and their accumulation is a hallmark of biofilm formation. M. smegmatis was mutated in gene MSMEG4722(orthologof M. tuberculosis Rv2509) (ΔMSMEG4722)which encodes a reductase involved in the final step of mycolic acid biosynthesis.
Using ΔMSMEG4722,this project explored the role of mycolic acid maturation in biofilm development, determined the relationship between lipids and complement activity with planktonic or biofilm bacteria.
Thin-layer chromatography of ΔMSMEG4722 biofilms displayed a loss of mature free mycolic acid compared to M. smegmatis, but accumulated un-reduced free mycolate. In both biofilm and planktonicΔMSMEG4722, distribution of the virulence factor trehalose dimycolate changed throughout the cell wall compared to M. smegmatis.
Flow cytometry analysis of the deposition of complement opsonin C3b revealed increased C3 on planktonic ΔMSMEG4722 compared to M. smegmatis, but this difference was not observed on bacteria from biofilms.
Evidence from this work suggests mycolic acid maturation is important for biofilm development and plays a role in complement activation on mycobacteria.
The evolution of Pseudomonas aeruginosa during short-term acute respiratory infections
Authors: Wheatley Rachel , Kapel Natalia , Caballero Julio Diaz , Paling Fleur , Sifakis Frangiscos , Ruzin Alexey , Timbermont Leen , Kluytmans Jan , Malhotra Surbhi , MacLean Craig 
Published: January 2020

Background. The emergence and spread of bacteria with resistance to multiple antimicrobial agents is raising the mortality rates associated with bacterial infections, and poses a fundamental threat to human health. Pseudomonas aeruginosais an opportunistic human pathogen that is responsible for 10-15% of health-care associated infections worldwide, and is known for its ability to rapidly develop enhanced resistance during the course of treating an infection.

Methods.
P. aeruginosa isolates have been collected from ICU patients in hospitals across Europe over a longitudinal sampling of short-term acute respiratory infection. Twelve isolates per patient per sampling of infection have been acquired. Genome sequencing and high-throughput phenotyping of growth rate and antibiotic resistance profile has been carried out.

Results and conclusions. Using high-throughput phenotyping and genome sequence data we have been able to characterise population diversity and variation in phenotypic resistance profile, growth rate and acquired resistance gene content of these isolates. A gradient of diversity was found within patient infections, ranging from monoclonal to multiple strains present. Large within-patient population diversity in phenotypic resistance profile and acquired resistance gene content could be observed in multiple sequence-type infections.
This research has been carried out in collaboration with the COMBACTE-MAGNET research consortium (Combatting Bacterial Resistance in Europe – Molecules against Gram-Negative Infections).
Lactate improves killing of Mycobacterium tuberculosis in human macrophages
Authors: Maoldomhnaigh Cilian Ó , Cox Donal , McQuaid Kate , Gogan Karl , Basdeo Sharee , Keane Joseph 
Published: January 2020

Mycobaterium tuberculosis (Mtb) kills more people than any other infectious agent worldwide. Our group has shown the importance of glycolysis in controlling intracellular Mtb growth in human macrophages1, which leads to increased lactate production. Therefore, we examined if lactate had an immunomodulatory effect on human monocyte derived macrophages (hMDM) infected with Mtb.
hMDM were adherence purified from healthy donor buffy coats with human serum for 6-8 days. Sodium L-Lactate was added 3 hours prior to infection with Mtb or stimulation with LPS (100 ng/ml). Macrophage phenotype and function was assessed by ELISA, flow cytometry and Seahorse metabolic-flux analysis. Bacillary killing was determined by colony forming units (CFU) after lysing infected hMDM, plating on middlebrook agar and counting 21 days later.
25 mM of lactate improves hMDM ability to control intracellular Mtb growth with a 55% reduction in CFU at day 5 post infection. The glycolytic response seen immediately following infection with Mtb or LPS stimulation was decreased with lactate. LPS-induced upregulation of activation markers was diminished by lactate.
Lactate is a product of aerobic glycolysis induced by infection and supports the intracellular killing of Mtb. Further research is required to elucidate the mechanism of this effect.
1. Gleeson, L. E. et al. Cutting Edge: Mycobacterium tuberculosis Induces Aerobic Glycolysis in Human Alveolar Macrophages That Is Required for Control of Intracellular Bacillary Replication. J. Immunol. 196, 2444–2449 (2016).
The molecular basis of antibiotic treatment failure in chronic urinary tract infections
Authors: Fatti Claudio Del , Jafari Nazila , Hubbard Alasdair , Khasriya Rajvinder , Roberts Adam , Rohn Jennifer 
Published: January 2020

Urinary tract infections (UTIs) are amongst the most common infections worldwide, and are becoming increasingly difficult to treat. In addition to the acceleration of classic antimicrobial resistance, recurrence after initial resolution is common. Our clinical experience is that chronically infected patients sometimes fail to respond to antibiotics predicted to be effective from culture-based sensitivity testing, while antibiotics predicted to be unsuitable can succeed. We hypothesized that the bladder environment could lead to differential bacterial gene expression, resulting in differences in minimum inhibitory concentration (MICs) compared with standard culture.
Here, using strains of Escherichia coli evolved in the lab to be resistant to amoxicillin–clavulanic acid, we present data that MICs differ depending on which media the assay is performed in (M9, ISO, LB, human urine), as well as in urine-containing supernatant enriched from urothelial organoids. Next, we examined the behaviour of patient-derived Enterococcus faecalis, one of the main causative agents of chronic UTIs in the elderly. We are in the process of evaluating the MIC of first-line UTI antibiotics using growth media supplemented with urine, to more closely mimic the native uropathogen environment. Moreover, we are characterising the resistance genes expressed in those differing environments using next generation sequencing technology and comparing the results with those obtained from bacteria grown on standard diagnostic media.
Our work demonstrates the danger of extrapolating biological behaviour from artificial culture substrates and may lead to better diagnostic tests and treatments for chronic UTI.
Socially messaging polycellular interactomes for innovative interventions in health and medicine
Authors: Reen F. Jerry 
Published: January 2020

The fast approaching post-antibiotic era has focused efforts on the search for new classes of antimicrobial compounds to arrest the increase in mortality levels attributed to microbial infections. Key to this has been the realisation that persistent infections arise from changes in polymicrobial communities, and the interactions between the protagonists within these communities can markedly affect the effectiveness of antibiotic-based interventions. Understanding the impact of key interactions within these ecosystems is key to priming the effectiveness of drug-based interventions.
We are pursuing a chemico-biological approach to investigate the molecular mechanisms underlying the anti-infective activity of small molecules from microbe-host interactomes. Evolved through co-existence, these novel molecular entities offer an effective means of pathogen control through a form of ‘chemical messaging’. Accessing the thesaurus of microbial messaging through rational design has led to a suite of distinct bioactive frameworks that can influence inter-species behaviours, moderating chronic and acute phases of virulence and pathogenesis in Pseudomonas aeruginosa and other pathogens. Similarly, at the interkingdom level, small molecular entities with anti-inflammatory and anti-cancer activities have been identified. Elucidating the molecular mechanisms underpinning the bioactive potential of these small molecules is key to unlocking their potential to deliver next generation medicines. This can only be done with a deeper understanding of the pathoadaptive phenotypic and genotypic heterogeneity that is emerging from clinical studies.
VarFish - Collaborative and Comprehensive Variant Analysis for Diagnosis and Research
Authors: Holtgrewe Manuel , Stolpe Oliver , Nieminen Mikko , Mundlos Stefan , Knaus Alexej , Kornak Uwe , Seelow Dominik , Segebrecht Lara , Spielmann Malte , Fischer-Zirnsak Björn , Boschann Felix , Scholl Ute , Ehmke Nadja , Beule Dieter 
Published: January 2020

ABSTRACTVarFish is a user-friendly web application for the quality control, filtering, prioritization, analysis, and user-based annotation of panel and exome variant data for rare disease genetics. It is capable of processing variant call files with single or multiple samples. The variants are automatically annotated with population frequencies, molecular impact, and presence in databases such as ClinVar. Further, it provides support for pathogenicity scores including CADD, MutationTaster, and phenotypic similarity scores. Users can filter variants based on these annotations and presumed inheritance pattern and sort the results by these scores. Filtered variants are listed with their annotations and many useful link-outs to genome browsers, other gene/variant data portals, and external tools for variant assessment. VarFish allows user to create their own annotations including support for variant assessment following ACMG-AMP guidelines. In close collaboration with medical practitioners, VarFish was designed for variant analysis and prioritization in diagnostic and research settings as described in the software’s extensive manual. The user interface has been optimized for supporting these protocols. Users can install VarFish on their own in-house servers where it provides additional lab notebook features for collaborative analysis and allows re-analysis of cases, e.g., after update of genotype or phenotype databases.