bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinematics of main-sequence stars from the Gaia DR2 and PMA proper motions
Authors: Velichko Anna B , Fedorov P N , Akhmetov V S 
Published: March 2020

ABSTRACTWe aim at analysis of kinematics of main-sequence stars from the GaiaDR2 and PMA catalogues as well as comparison of kinematic parameters derived from their proper motions. We decompose the stellar velocity field on to a set of vector spherical harmonics (VSH), and, using the relations between the decomposition coefficients and the Ogorodnikov–Milne (O–M) model parameters, calculate the latter. The method of VSH allowed to detect all systematic constituents present in the GaiaDR2 and PMA stellar velocity fields. We notice incompleteness of the O–M model, discuss the kinematic parameters derived within its framework, as well as significant decomposition coefficients that do not have analogues within this model. For separate analysis of the kinematic parameters in the Northern and Southern Galactic hemispheres, we apply the decomposition on to a set of zonal VSH (ZVSH). Modelling the stellar velocity field allowed to confirm the causes of some significant beyond-the-model harmonics. Based on stellar proper motions from the Gaia DR2 and PMA catalogues, we confirm the previous conclusion that the values of ω1 and $M^+_{23}$ O–M model parameters derived in the Northern and Southern Galactic hemispheres have opposite signs. This fact takes place due to a vertical gradient of the linear rotation velocity about the Galactic centre. We estimate influence of the vertical gradient on the value of solar velocity component Y⊙. We confirm that the beyond-the-model coefficients t211 and s310 are caused by the vertical gradient as well.
Partial Normalization of Biomarkers of Inflammation and Immune Activation Among Virally Suppressed Men With HIV Infection and High ART Adherence
Authors: Castillo-Mancilla Jose R , Brown Todd T , Palella Frank J , Macatangay Bernard J C , Breen Elizabeth C , Jacobson Lisa P , Wada Nikolas I 
Published: March 2020

AbstractBackgroundThe objective of this study was to investigate whether 100% antiretroviral therapy (ART) adherence in men with HIV (MWH) is associated with normalization of concentrations of biomarkers of inflammation and immune activation compared with HIV-uninfected men.MethodsWe analyzed person-visits with available biomarker data from the Multicenter AIDS Cohort Study (MACS) among MWH receiving ART with HIV RNA &lt;50 copies/mL and among HIV-uninfected men. Self-reported adherence was classified as 100% if no missed ART doses in the past 4 days were reported. We evaluated associations between ART adherence and concentrations of 24 serum biomarkers compared with HIV-uninfected visits using a generalized gamma model, adjusting for potential confounders.ResultsPerson-visits (2565 from MWH reporting 100% ART adherence and 1588 from HIV-uninfected men) from a total of 1469 men were included in the analysis. Serum concentrations of interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R), IL-1β, interferon-γ (IFN-γ), chemokine C-C motif ligand 2 (CCL2), and CCL14 from person-visits among MWH who reported 100% adherence were similar to HIV-uninfected person-visits. Comparatively higher concentrations of 11 biomarkers and lower concentrations of 7 biomarkers were observed in person-visits from MWH who reported 100% ART adherence, compared with HIV-uninfected person-visits.ConclusionsAlthough MWH with virologic suppression who reported 100% ART adherence exhibited overall higher concentrations of biomarkers of inflammation and immune activation compared with HIV-uninfected men, some biomarker concentrations were similar in both groups. These findings suggest that optimal ART adherence could have clinical implications beyond achieving and sustaining viral suppression.
RNA-based therapies in animal models of Leber congenital amaurosis causing blindness
Authors: Wang Xia , Shan Xianghong , Gregory-Evans Kevin , Gregory-Evans Cheryl Y 
Published: March 2020

Abstract
Leber congenital amaurosis (LCA) is a severe, genetically heterogeneous recessive eye disease in which ~ 35% of gene mutations are in-frame nonsense mutations coding for loss-of-function premature termination codons (PTCs) in mRNA. Nonsense suppression therapy allows read-through of PTCs leading to production of full-length protein. A limitation of nonsense suppression is that nonsense-mediated decay (NMD) degrades PTC-containing RNA transcripts. The purpose of this study was to determine whether inhibition of NMD could improve nonsense suppression efficacy in vivo. Using a high-throughput approach in the recessive cep290 zebrafish model of LCA (cep290;Q1223X), we first tested the NMD inhibitor Amlexanox in combination with the nonsense suppression drug Ataluren. We observed reduced retinal cell death and improved visual function. With these positive data, we next investigated whether this strategy was also applicable across species in two mammalian models: Rd12 (rpe65;R44X) and Rd3 (rd3;R107X) mouse models of LCA. In the Rd12 model, cell death was reduced, RPE65 protein was produced, and in vivo visual function testing was improved. We establish for the first time that the mechanism of action of Amlexanox in Rd12 retina was through reduced UPF1 phosphorylation. In the Rd3 model, however, no beneficial effect was observed with Ataluren alone or in combination with Amlexanox. This variation in response establishes that some forms of nonsense mutation LCA can be targeted by RNA therapies, but that this needs to be verified for each genotype. The implementation of precision medicine by identifying better responders to specific drugs is essential for development of validated retinal therapies.
Protein Profiles of Lipid Droplets during the Hypersensitive Defense Response of Arabidopsis against Pseudomonas Infection
Authors: Fernández-Santos Rubén , Izquierdo Yovanny , López Ana , Muñiz Luis , Martínez Marta , Cascón Tomás , Hamberg Mats , Castresana Carmen 
Published: March 2020

Abstract
Lipid droplets (LDs) have classically been viewed as seed storage particles, yet they are now emerging as dynamic organelles associated with developmental and stress responses. Nevertheless, their involvement in plant immunity has still been little studied. Here, we found LD accumulation in Arabidopsis thaliana leaves that induced a hypersensitive response (HR) after Pseudomonas infection. We established a protocol to reproducibly isolate LDs and to analyze their protein content. The expression of GFP fusion proteins in Nicotiana benthamiana and in transgenic Arabidopsis lines validated the LD localization of glycerol-3-phosphate acyltransferase 4 (GPAT4) and 8 (GPAT8), required for cutin biosynthesis. Similarly, we showed LD localization of α-dioxygenase1 (α-DOX1) and caleosin3 (CLO3), involved in the synthesis of fatty acid derivatives, and that of phytoalexin-deficient 3 (PAD3), which is involved in camalexin synthesis. We found evidence suggesting the existence of different populations of LDs, with varying protein contents and distributions. GPAT4 and GPAT8 were associated with LDs inside stomata and surrounding cells of untreated leaves, yet they were mainly confined to LDs in guard cells after bacterial inoculation. By contrast, α-DOX1 and PAD3 were associated with LDs in the epidermal cells of HR-responding leaves, with PAD3 mostly restricted to cells near dead tissue, while CLO3 had a more ubiquitous distribution. As such, the nature of the proteins identified, together with the phenotypic examination of selected mutants, suggests that LDs participate in lipid changes and in the production and transport of defense components affecting the interaction of plants with invading pathogens.
Renal deposits of complement factors as predictors of end-stage renal disease and death in patients with lupus nephritis
Authors: Koopman Jacob J E , Rennke Helmut G , Leatherwood Cianna , Speyer Cameron B , D’Silva Kristin , McMahon Gearoid M , Waikar Sushrut S , Costenbader Karen H 
Published: March 2020

Abstract

Objective
Lupus nephritis (LN) increases the risks of end-stage renal disease (ESRD) and death, but these risks are difficult to estimate. Since complement factors play an essential role in the pathogenesis and are deposited in the kidneys as C1q and C3, we studied whether these deposits predict ESRD and death in patients with LN.

Methods
We collected demographic, clinical and pathological data from 183 adult patients with LN classes II–V diagnosed with a first native kidney biopsy. Pathological data included the localization and intensity of immunofluorescence staining of C1q and C3. We obtained dates of incident ESRD and death from the United States Renal Data System and National Death Index, respectively, and evaluated survival curves and hazard ratios for ESRD and death as a composite outcome and as separate outcomes.

Results
The presence and intensity of deposits of C1q and C3 in glomeruli, tubular walls and vascular walls differed between classes and were associated with known unfavourable prognostic factors, such as hypertension, hypoalbuminemia and hypocomplementemia. However, over a median follow-up of 7.5 years, their presence and intensity were associated with neither survival free of ESRD and death nor hazard ratios for ESRD and death.

Conclusion
Renal deposits of complement factors did not predict ESRD and death in patients with LN.
Global Risks in the Currency Market*
Authors: Panayotov George 
Published: March 2020

Abstract
Global risks allow theoretical models of the currency market to explain currency risk premia. Yet, there is no consensus in the empirical literature on which factors can represent global risks. We develop an asset pricing test for global risk factors that relies on the key assumption of a distinct US global risk exposure. Using perspective-invariant test assets that are particularly suitable for studying global risks, we apply the test on a large set of factors used in recent studies of currency risk. We find that only equity market risk can represent a global risk in the currency market.
Implementing upfront mobile digital chest x-ray for tuberculosis diagnosis in India—feasibility and benefits
Authors: Datta Bornali , Prakash Ashish , Ford David , Tripathy Jaya Prasad , Goyal Pinky , Singh Shreya , Singh Veena , Jaiswal Anand , Trehan Naresh 
Published: March 2020

Abstract

Background
The Tuberculosis (TB) Control Program in India changed the TB diagnostic algorithm and recommended sputum testing and chest x-ray (CXR) for presumptive TB up front. There is no experience of testing this algorithm in routine field settings.

Methods
In a public–private partnership (PPP), a private hospital provided mobile digital CXR services (mounted on a van) to complement the existing diagnostic services of sputum microscopy and GeneXpert testing. All presumptive TB patients (cough &gt;2 weeks) underwent CXR and sputum microscopy, and GeneXpert testing if eligible (smear-negative CXR suggestive of TB).

Results
All 2973 presumptive TB patients underwent CXR and sputum microscopy; 471 (15.8%) had abnormal CXR findings suggestive of TB, 129 (4.3%) were smear positive and 17 were extrapulmonary TB. Of the remaining 325 with smear-negative and CXR suggestive of TB, 147 (45.2%) underwent GeneXpert testing, yielding 32 positives (21.8%). Of the remaining 178 with no GeneXpert test done, 106 (60.0%) had CXR definitely suggesting TB (clinically diagnosed TB). Thus a total of 284 cases of TB (161 microbiologically confirmed, 106 clinically diagnosed, 17 extrapulmonary TB) were identified, giving a potential diagnostic yield of 19.6%.

Conclusions
Systematic screening with mobile digital X-ray service via a PPP model integrated into the national program is feasible and scalable with a high yield.
Putting science back into microbial ecology: a question of approach
Authors: Prosser James I. 
Published: March 2020

Microbial ecology, the scientific study of interactions between natural microbial communities and their environments, has been facilitated by the application of molecular and ‘omics’-based techniques that overcome some of the limitations of cultivation-based studies. This has increased emphasis on community ecology and ‘microbiome’ studies, but the majority address technical, rather than scientific challenges. Most are descriptive, do not address scientific aims or questions and are not designed to increase understanding or test hypotheses. The term ‘hypothesis’ is increasingly misused and critical testing of ideas or theory is restricted to a small minority of studies. This article discusses current microbial ecology research within the context of four approaches: description, induction, inference to the best explanation and deduction. The first three of these do not follow the established scientific method and are not based on scientific ecological questions. Observations are made and sometimes compared with published data, sometimes with attempts to explain findings in the context of existing ideas or hypotheses, but all lack objectivity and are biased by the observations made. By contrast, deductive studies address ecological questions and attempt to explain currently unexplained phenomena through the construction of hypotheses, from mechanism-based assumptions, that generate predictions that are then tested experimentally. Identification of key scientific questions, research driven by meaningful hypotheses and adoption of scientific method are essential for progress in microbial ecology, rather than the current emphasis on descriptive approaches that address only technical challenges. It is, therefore, imperative that we carefully consider and define the fundamental scientific questions that drive our own research and focus on ideas, concepts and hypotheses that can increase understanding, and only then consider which techniques are required for experimental testing.
This article is part of the theme issue ‘Conceptual challenges in microbial community ecology’.
Ecological and evolutionary mechanisms underlying patterns of phylosymbiosis in host-associated microbial communities
Authors: Kohl Kevin D. 
Published: March 2020

Phylosymbiosis, where similarities in host-associated microbial communities recapitulate the phylogeny of their hosts, is a newly recognized yet pervasive pattern in the field of host–microbe interactions. While phylosymbiosis has been documented across many systems, we still have a poor understanding of the mechanisms that underlie this emergent pattern. Host selection of the microbiome is a widely cited mechanism, yet other basic ecological and evolutionary processes (dispersal, drift and diversification) may also be at play. This paper discusses the roles that each of these processes and their interactions may play in yielding phylosymbiotic signals across hosts. Finally, this paper will identify open questions and methods that are required to better understand the relative contributions of these basic processes to phylosymbiosis. Given that phylosymbiosis has been shown to relate to functional components of host fitness, understanding the processes that contribute to these patterns will be important for our understanding of the ecology and evolution of host–microbe interactions.This article is part of the theme issue ‘Conceptual challenges in microbial community ecology’.
How can microbial population genomics inform community ecology?
Authors: VanInsberghe David , Arevalo Philip , Chien Diana , Polz Martin F. 
Published: March 2020

Populations are fundamental units of ecology and evolution, but can we define them for bacteria and archaea in a biologically meaningful way? Here, we review why population structure is difficult to recognize in microbes and how recent advances in measuring contemporary gene flow allow us to identify clearly delineated populations among collections of closely related genomes. Such structure can arise from preferential gene flow caused by coexistence and genetic similarity, defining populations based on biological mechanisms. We show that such gene flow units are sufficiently genetically isolated for specific adaptations to spread, making them also ecological units that are differentially adapted compared to their closest relatives. We discuss the implications of these observations for measuring bacterial and archaeal diversity in the environment. We show that operational taxonomic units defined by 16S rRNA gene sequencing have woefully poor resolution for ecologically defined populations and propose monophyletic clusters of nearly identical ribosomal protein genes as an alternative measure for population mapping in community ecological studies employing metagenomics. These population-based approaches have the potential to provide much-needed clarity in interpreting the vast microbial diversity in human and environmental microbiomes.
This article is part of the theme issue ‘Conceptual challenges in microbial community ecology’.
Improving estimation of Parkinson’s disease risk - The enhanced PREDICT-PD algorithm
Authors: Bestwick Jonathan P. , Auger Stephen D. , Simonet Cristina , Rees Richard N. , Rack Daniel , Jitlal Mark , Giovannoni Gavin , Lees Andrew J. , Cuzick Jack , Schrag Anette E. , Noyce Alastair J. 
Published: March 2020

ABSTRACTBackgroundWe previously reported a basic algorithm to identify risk of Parkinson’s disease (PD) using published data on risk factors and prodromal features. Using this algorithm, the PREDICT-PD study identified individuals at increased risk of PD, using tapping speed, hyposmia and REM sleep behaviour disorder (RBD) as “intermediate” markers of prodromal PD until sufficient incident cases accrued.ObjectivesTo develop and test an enhanced algorithm which incorporates these intermediate markers into the risk model.MethodsIntermediate markers were incorporated into risk estimates, and likelihood ratios for both the presence and absence of risk factors were used. Risk estimates were compared using the enhanced and the basic algorithm in members of the PREDICT-PD pilot cohort.ResultsThe enhanced PREDICT-PD algorithm yielded a much greater range of risk estimates than the basic algorithm (346 - 784-fold difference between the 10th and 90th centiles vs 10 12-fold respectively). There was a greater increase in risk of PD with increasing risk scores for the enhanced algorithm than for the basic algorithm (hazard ratios per one standard deviation increase in log risk of 2.73 [95% CI 1.68 – 4.45; p<0.001] versus 1.47 [95% CI 0.86 2.51; p=0.16] respectively). Estimates from the enhanced algorithm also correlated more closely with subclinical striatal DaT-SPECT dopamine depletion (R2=0.14, p=0.010 vs R2=0.043, p=0.17).ConclusionsIncorporating the previous intermediate markers of prodromal PD and using likelihood ratios improved the accuracy of the PREDICT-PD prediction algorithm for PD.
Impact of the MyProstateScore (MPS) test on the clinical decision to undergo prostate biopsy: results from a contemporary academic practice
Authors: Lebastchi Amir H. , Russell Christopher M. , Niknafs Yashar S. , Eyrich Nicholas W. , Chopra Zoey , Botbyl Rachel , Kabeer Rana , Osawa Takahiro , Siddiqui Javed , Siddiqui Rabia , Davenport Matthew S. , Mehra Rohit , Tomlins Scott A. , Kunju Lakshimi P. , Chinnaiyan Arul M. , Wei John T. , Tosoian Jeffrey J. , Morgan Todd M. 
Published: March 2020

AbstractObjectiveTo evaluate the association of the MyProstateScore (MPS) urine test on the decision to undergo biopsy in men referred for prostate biopsy at a contemporary academic urology practice.MethodsMPS testing was offered as an alternative to immediate biopsy in men referred to the University of Michigan for prostate biopsy from October 2013 through October 2016. The primary endpoint was the decision to perform biopsy. The proportion of patients who underwent biopsy was calculated across MPS quintiles and compared to predicted risk scores from the Prostate Cancer Prevention Trial risk calculator (PCPTrc). Analyses were performed in the overall referral population and the intended-use population (PSA 3-10 ng/ml or PSA <3 ng/ml and abnormal DRE) and stratified by the use of multiparametric magnetic resonance imaging (mpMRI). The associations of PCPTrc, MPS, and mpMRI with the decision to undergo biopsy were explored in a multivariable logistic regression model.ResultsOf 248 patients, 134 (54%) proceeded to prostate biopsy. Clinical variables, PSA, and PCPTrc score did not significantly differ based on the decision to undergo biopsy, while MPS was significantly higher in biopsied patients (median 29 vs. 14, p<0.001). The use of biopsy was strongly associated with MPS, with biopsy rates of 26%, 38%, 58%, 90%, and 85% in the first through fifth MPS quintiles, respectively (p<0.001). By contrast, biopsy rates were 51%, 47%, 52%, 69%, and 52% by increasing PCPTrc score quintile (p=0.3). The association of MPS with biopsy persisted upon stratification by use of mpMRI. On multivariable analysis, MPS was strongly associated with the decision to undergo biopsy when modeled as both a continuous variable (odds ratio [OR] 1.05 per 1 unit increase, 95% confidence interval [CI] 1.04-1.08; <0.001) and binary variable (OR 7.76, 95% CI 4.14-14.5; p<0.001). These findings were consistent in the overall and intended-use populations.ConclusionIn a cohort of patients who underwent clinical MPS testing as an alternative to immediate prostate biopsy, 46% were able to avoid biopsy and increasing MPS was strongly associated with biopsy rates. These findings were robust to the use of mpMRI and consistent across pertinent subpopulations. Overall, these data suggest that the MPS assay may substantially reduce the number of men undergoing prostate needle biopsy.
Now-casting the COVID-19 epidemic: The use case of Japan, March 2020
Authors: Glöckner Stephan , Krause Gérard , Höhle Michael 
Published: March 2020

AbstractBackgroundReporting delays in disease surveillance impair the ability to assess the current dynamic of an epidemic. In continuously updated epidemic curves, case numbers for the most recent epidemic week or day usually appear to be lower than the previous, suggesting a decline of the epidemic. In reality, the epidemic curve may still be on the rise, because reporting delay prevents the most recent cases to appear in the case count. In context of the COVID-19 epidemic and for countries planning large international gatherings, such as the Summer Olympic Games in Japan 2020, the ability to assess the actual stage of an epidemic is of outmost importance.MethodsWe applied now-casting onto COVID-19 data provided by the nCoV-2019 Data Working Group to evaluate the true count of cases, by taking into account reporting delays occurring between date of symptom onset and date of confirmation.FindingsWe calculated a decrease of reporting delay, from a median delay of ten days in calendar week four 2020 to six days in calendar week eight, resulting in an overall mean of 4.3 days. The confidence intervals of the now-casting indicated an increase of cases in the last reporting days, while case country in that same time period suggested a decline.InterpretationAs a specific use case this tool may be of particular value for the challenging risk assessment and risk communication in the context of the Summer Olympic Games in Japan 2020 and similar situations elsewhere.