bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allele-specific multi-sample copy number segmentation in ASCAT
Authors: Ross Edith M. , Haase Kerstin , Van Loo Peter , Markowetz Florian 
Published: May 2020

Abstract

Motivation
Allele-specific copy number alterations are commonly used to trace the evolution of tumours. A key step of the analysis is to segment genomic data into regions of constant copy number. For precise phylogenetic inference, breakpoints shared between samples need to be aligned to each other.

Results
Here, we present asmultipcf, an algorithm for allele-specific segmentation of multiple samples that infers private and shared segment boundaries of phylogenetically related samples. The output of this algorithm can directly be used for allele-specific copy number calling using ASCAT.

Availability and implementation
asmultipcf is available as part of the ASCAT R package (version ≥2.5) from github.com/Crick-CancerGenomics/ascat/.
TissUUmaps: interactive visualization of large-scale spatial gene expression and tissue morphology data
Authors: Solorzano Leslie , Partel Gabriele , Wählby Carolina 
Published: May 2020

Abstract

Motivation
Visual assessment of scanned tissue samples and associated molecular markers, such as gene expression, requires easy interactive inspection at multiple resolutions. This requires smart handling of image pyramids and efficient distribution of different types of data across several levels of detail.

Results
We present TissUUmaps, enabling fast visualization and exploration of millions of data points overlaying a tissue sample. TissUUmaps can be used both as a web service or locally in any computer, and regions of interest as well as local statistics can be extracted and shared among users.

Availability and implementation
TissUUmaps is available on github at github.com/wahlby-lab/TissUUmaps. Several demos and video tutorials are available at http://tissuumaps.research.it.uu.se/howto.html.

Supplementary information
Supplementary data are available at Bioinformatics online.
Dopamine is associated with prioritization of reward-associated memories in Parkinson’s disease
Authors: Sharp Madeleine E , Duncan Katherine , Foerde Karin , Shohamy Daphna 
Published: May 2020

Abstract
Patients with Parkinson’s disease have reduced reward sensitivity related to dopaminergic neuron loss, which is associated with impairments in reinforcement learning. Increasingly, however, dopamine-dependent reward signals are recognized to play an important role beyond reinforcement learning. In particular, it has been shown that reward signals mediated by dopamine help guide the prioritization of events for long-term memory consolidation. Meanwhile, studies of memory in patients with Parkinson’s disease have focused on overall memory capacity rather than what is versus what isn’t remembered, leaving open questions about the effect of dopamine replacement on the prioritization of memories by reward and the time-dependence of this effect. The current study sought to fill this gap by testing the effect of reward and dopamine on memory in patients with Parkinson’s disease. We tested the effect of dopamine modulation and reward on two forms of long-term memory: episodic memory for neutral objects and memory for stimulus-value associations. We measured both forms of memory in a single task, adapting a standard task of reinforcement learning with incidental episodic encoding events of trial-unique objects. Objects were presented on each trial at the time of feedback, which was either rewarding or not. Memory for the trial-unique images and for the stimulus-value associations, and the influence of reward on both, was tested immediately after learning and 2 days later. We measured performance in Parkinson’s disease patients tested either ON or OFF their dopaminergic medications and in healthy older control subjects. We found that dopamine was associated with a selective enhancement of memory for reward-associated images, but that it did not influence overall memory capacity. Contrary to predictions, this effect did not differ between the immediate and delayed memory tests. We also found that while dopamine had an effect on reward-modulated episodic memory, there was no effect of dopamine on memory for stimulus-value associations. Our results suggest that impaired prioritization of cognitive resource allocation may contribute to the early cognitive deficits of Parkinson’s disease.
Impact of Intrapartum Oral Azithromycin on the Acquired Macrolide Resistome of Infants’ Nasopharynx: A Randomized Controlled Trial
Authors: Bojang Abdoulie , Baines Sarah L , Camara Bully , Guerillot Romain , Donovan Liam , Marqués Raquel Sánchez , Secka Ousman , D’Alessandro Umberto , Bottomley Christian , Howden Benjamin P , Roca Anna 
Published: May 2020

Abstract

In a post hoc analysis of samples from an intrapartum azithromycin randomized clinical trial, we found that children whose mothers had been treated with the drug had higher prevalence of macrolide-resistance genes msr(A) and ermC at 28 days but not at 12 months. The 2 genes were positively associated in the nasopharynx.

Clinical Trials Registration
NCT1800942.
Declines in Pneumonia Mortality Following the Introduction of Pneumococcal Conjugate Vaccines in Latin American and Caribbean Countries
Authors: de Oliveira Lucia H , Shioda Kayoko , Valenzuela Maria Tereza , Janusz Cara B , Rearte Analía , Sbarra Alyssa N , Warren Joshua L , Toscano Cristiana M , Weinberger Daniel M ,   Multinational Study for PCV Impact in Mortality Study Team
Published: May 2020

Abstract

Background
Pneumococcal conjugate vaccines (PCVs) are recommended for use in pediatric immunization programs worldwide. Few data are available on their effect against mortality. We present a multicountry evaluation of the population-level impact of PCVs against death due to pneumonia in children &lt; 5 years of age.

Methods
We obtained national-level mortality data between 2000 and 2016 from 10 Latin American and Caribbean countries, using the standardized protocol. Time series models were used to evaluate the decline in all-cause pneumonia deaths during the postvaccination period while controlling for unrelated temporal trends using control causes of death.

Results
The estimated declines in pneumonia mortality following the introduction of PCVs ranged from 11% to 35% among children aged 2–59 months in 5 countries: Colombia (24% [95% credible interval {CrI}, 3%–35%]), Ecuador (25% [95% CrI, 4%–41%]), Mexico (11% [95% CrI, 3%–18%]), Nicaragua (19% [95% CrI, 0–34%]), and Peru (35% [95% CrI, 20%–47%]). In Argentina, Brazil, and the Dominican Republic, the declines were not detected in the aggregated age group but were detected in certain age strata. In Guyana and Honduras, the estimates had large uncertainty, and no declines were detected. Across the 10 countries, most of which have low to moderate incidence of pneumonia mortality, PCVs have prevented nearly 4500 all-cause pneumonia deaths in children 2–59 months since introduction.

Conclusions
Although the data quality was variable between countries, and the patterns varied across countries and age groups, the balance of evidence suggests that mortality due to all-cause pneumonia in children declined after PCV introduction. The impact could be greater in populations with a higher prevaccine burden of pneumonia.
Decreased Time From Human Immunodeficiency Virus Diagnosis to Care, Antiretroviral Therapy Initiation, and Virologic Suppression during the Citywide RAPID Initiative in San Francisco
Authors: Bacon Oliver , Chin Jennie , Cohen Stephanie E , Hessol Nancy A , Sachdev Darpun , Coffey Susa , Scheer Susan , Buchbinder Susan , Havlir Diane V , Hsu Ling 
Published: May 2020

Abstract

Background
Early virologic suppression (VS) after human immunodeficiency virus (HIV) infection improves individual health outcomes and decreases onward transmission. In San Francisco, immediate antiretroviral therapy (ART) at HIV diagnosis was piloted in 2013–2014 and expanded citywide in 2015 in a rapid start initiative to link all new diagnoses to care within 5 days and start ART at the first care visit.

Methods
HIV providers and linkage navigators were trained on a rapid start protocol with sites caring for vulnerable populations prioritized. Dates of HIV diagnosis, first care visit, ART initiation, and VS were abstracted from the San Francisco Department of Public Health HIV surveillance registry.

Results
During 2013–2017, among 1354 new HIV diagnoses in San Francisco, median days from diagnosis to first VS decreased from 145 to 76 (48%; P &lt; .0001) and from first care visit to ART initiation decreased from 28 to 1 (96%; P &lt; .0001). By 2017, 28% of new diagnoses had a rapid start, which was independently associated with Latinx ethnicity (AOR, 1.73; 95% CI, 1.15–2.60) and recent year of diagnosis (2017; AOR, 16.84; 95% CI, 8.03–35.33). Persons with a rapid ART start were more likely to be virologically suppressed within 12 months of diagnosis than those with a non-rapid start (RR, 1.17; 95% CI, 1.10–1.24).

Conclusions
During a multisector initiative to optimize ART initiation, median time from diagnosis to VS decreased by nearly half. Immediate ART at care initiation was achieved across many, but not all, populations, and was associated with improved suppression rates.
Clinical Correlations of Programmed Cell Death Ligand 1 Status in Liquid and Standard Biopsies in Breast Cancer
Authors: Jacot William , Mazel Martine , Mollevi Caroline , Pouderoux Stéphane , D’Hondt Véronique , Cayrefourcq Laure , Bourgier Céline , Boissiere-Michot Florence , Berrabah Fella , Lopez-Crapez Evelyne , Bidard François-Clément , Viala Marie , Maudelonde Thierry , Guiu Séverine , Alix-Panabières Catherine 
Published: May 2020

Abstract

Background
Data regarding the prognostic value of programmed cell death ligand 1 (PD-L1) expression on circulating tumor cells (CTCs) are lacking. However, CTCs could represent an alternative approach to serial biopsies, allowing real-time monitoring of cancer phenotype.

Methods
We evaluated, in a dedicated prospective clinical trial, the clinicopathological correlations and prognostic value of PD-L1(+)-CTCs in 72 patients with metastatic breast cancer (MBC).

Results
Eighteen of 56 patients with available archival tissue presented at least one positive (≥1%) PD-L1 tumor sample. Baseline CTCs and PD-L1(+)-CTCs were detected in 57 (79.2%) and 26 (36.1%) patients. No significant correlation was found between PD-L1 tumors and CTC expression. In univariate analysis, triple negative (TN) phenotype, number of metastatic treatments, &gt;2 metastatic sites, ≥5 CTCs and PD-L1(+)-CTCs were significantly associated with progression-free survival, while tissue PD-L1 expression was not. In multivariate analysis, TN phenotype, number of metastatic treatments and of metastatic sites were the only 3 variables independently associated with progression-free survival. Progesterone receptor negativity, TN phenotype, &gt;2 metastatic sites and ≥5 CTCs were significantly associated with overall survival in univariate analysis. In multivariable analysis, TN phenotype and &gt;2 metastatic sites were the only 2 independent variables.

Conclusions
Unlike PD-L1(+)-tumor, PD-L1(+)-CTCs correlate to survival in MBC. Reappraisal of the role of PD-L1 expression by tumor tissue and by CTCs under anti-PD-1/PD-L1 treatment is necessary to evaluate its predictive value and potential role as a stratifying factor in strategies and trials for MBC patients with MBC.

Clinical trial registration
NCT02866149
The Vanishing Procyclicality of Labour Productivity
Authors: Galí Jordi , van Rens Thijs 
Published: May 2020

AbstractWe document two changes in post-war US macroeconomic dynamics: the procyclicality of labour productivity vanished, and the relative volatility of employment rose. We propose an explanation for these changes that is based on reduced hiring frictions due to improvements in information about the quality of job matches and the resulting decline in turnover. We develop a simple model with hiring frictions and variable effort to illustrate the mechanisms underlying our explanation. We show that our model qualitatively and quantitatively matches the observed changes in business cycle dynamics.
Agents of Socialization and Female Migrants’ Employment: The Influence of Mothers and the Country Context
Authors: Krieger Magdalena 
Published: May 2020

Abstract
Women around the world are on the move but find it difficult to secure jobs. Employment is vital for migrant integration as it affords financial security, autonomy in the family and helps to establish social contacts. Besides human capital, previous research has looked into ethnic origin and specific source country aspects as drivers of female migrant employment. By contrast, ideas of adolescence as the ‘impressionable’ years and individuals’ exposure to female employment at that time have not yet entered the discussion. However, these theoretical notions have previously been found to be highly predictive of employment in adulthood for natives. This study further investigates these theoretical ideas by using data on 2,047 female immigrants from the German Socio-Economic Panel. Female migrants’ employment and hours worked are analysed in multivariate regressions. The analyses focus on female migrants’ adolescent experiences with female employment in their family—namely, whether their mother worked—and in the broader labour market—measured by the female to male labour force participation rate—as explanatory variables. These two experiences are retrospectively captured for respondents at age 15. Analyses highlight the deep embeddedness of individuals in home country social norms and the power of role models during youth for later employment.
Performance of A Priori and A Posteriori Calibration Strategies in Divergence Time Estimation
Authors: Beavan Alan J S , Donoghue Philip C J , Beaumont Mark A , Pisani Davide 
Published: May 2020

Abstract
Relaxed molecular clock methods allow the use of genomic data to estimate divergence times across the tree of life. This is most commonly achieved in Bayesian analyses where the molecular clock is calibrated a priori through the integration of fossil information. Alternatively, fossil calibrations can be used a posteriori, to transform previously estimated relative divergence times that were inferred without considering fossil information, into absolute divergence times. However, as branch length is the product of the rate of evolution and the duration in time of the considered branch, the extent to which a posteriori calibrated, relative divergence time methods can disambiguate time and rate, is unclear. Here, we use forward evolutionary simulations and compare a priori and a posteriori calibration strategies using different molecular clock methods and models. Specifically, we compare three Bayesian methods, the strict clock, uncorrelated clock and autocorrelated clock, and the non-Bayesian algorithm implemented in RelTime. We simulate phylogenies with multiple, independent substitution rate changes and show that correct timescales cannot be inferred without the use of calibrations. Under our simulation conditions, a posteriori calibration strategies almost invariably inferred incorrect rate changes and divergence times. The a priori integration of fossil calibrations is fundamental in these cases to improve the accuracy of the estimated divergence times. Relative divergence times and absolute timescales derived by calibrating relative timescales to geological time a posteriori appear to be less reliable than a priori calibrated, timescales.
Recurrent Loss of abaA, a Master Regulator of Asexual Development in Filamentous Fungi, Correlates with Changes in Genomic and Morphological Traits
Authors: Mead Matthew E , Borowsky Alexander T , Joehnk Bastian , Steenwyk Jacob L , Shen Xing-Xing , Sil Anita , Rokas Antonis 
Published: May 2020

AbstractGene regulatory networks (GRNs) drive developmental and cellular differentiation, and variation in their architectures gives rise to morphological diversity. Pioneering studies in Aspergillus fungi, coupled with subsequent work in other filamentous fungi, have shown that the GRN governed by the BrlA, AbaA, and WetA proteins controls the development of the asexual fruiting body or conidiophore. A specific aspect of conidiophore development is the production of phialides, conidiophore structures that are under the developmental control of AbaA and function to repetitively generate spores. Fungal genome sequencing has revealed that some filamentous fungi lack abaA, and also produce asexual structures that lack phialides, raising the hypothesis that abaA loss is functionally linked to diversity in asexual fruiting body morphology. To examine this hypothesis, we carried out an extensive search for the abaA gene across 241 genomes of species from the fungal subphylum Pezizomycotina. We found that abaA was independently lost in four lineages of Eurotiomycetes, including from all sequenced species within the order Onygenales, and that all four lineages that have lost abaA also lack the ability to form phialides. Genetic restoration of abaA from Aspergillus nidulans into Histoplasma capsulatum, a pathogenic species from the order Onygenales that lacks an endogenous copy of abaA, did not alter Histoplasma conidiation morphology but resulted in a marked increase in spore viability. We also discovered that species lacking abaA contain fewer AbaA binding motifs in the regulatory regions of orthologs of some AbaA target genes, suggesting that the asexual fruiting body GRN of organisms that have lost abaA has likely been rewired. Our results provide an illustration of how repeated losses of a key regulatory transcription factor have contributed to the diversity of an iconic fungal morphological trait.
Proteomics of Osmoregulatory Responses in Threespine Stickleback Gills
Authors: Li Johnathon , Kültz Dietmar 
Published: May 2020

Synopsis
The gill proteome of threespine sticklebacks (Gasterosteus aculeatus) differs greatly in populations that inhabit diverse environments characterized by different temperature, salinity, food availability, parasites, and other parameters. To assess the contribution of a specific environmental parameter to such differences it is necessary to isolate its effects from those of other parameters. In this study the effect of environmental salinity on the gill proteome of G. aculeatus was isolated in controlled mesocosm experiments. Salinity-dependent changes in the gill proteome were analyzed by Liquid chromatography/Tandem mass spectrometry data-independent acquisition (DIA) and Skyline. Relative abundances of 1691 proteins representing the molecular phenotype of stickleback gills were quantified using previously developed MSMS spectral and assay libraries in combination with DIA quantitative proteomics. Non-directional stress responses were distinguished from osmoregulatory protein abundance changes by their consistent occurrence during both hypo- and hyper-osmotic salinity stress in six separate mesocosm experiments. If the abundance of a protein was consistently regulated in opposite directions by hyper- versus hypo-osmotic salinity stress, then it was considered an osmoregulatory protein. In contrast, if protein abundance was consistently increased irrespective of whether salinity was increased or decreased, then it was considered a non-directional response protein. KEGG pathway analysis revealed that the salivary secretion, inositol phosphate metabolism, valine, leucine, and isoleucine degradation, citrate cycle, oxidative phosphorylation, and corresponding endocrine and extracellular signaling pathways contain most of the osmoregulatory gill proteins whose abundance is directly proportional to environmental salinity. Most proteins that were inversely correlated with salinity map to KEGG pathways that represent proteostasis, immunity, and related intracellular signaling processes. Non-directional stress response proteins represent fatty and amino acid degradation, purine metabolism, focal adhesion, mRNA surveillance, phagosome, endocytosis, and associated intracellular signaling KEGG pathways. These results demonstrate that G. aculeatus responds to salinity changes by adjusting osmoregulatory mechanisms that are distinct from transient non-directional stress responses to control compatible osmolyte synthesis, transepithelial ion transport, and oxidative energy metabolism. Furthermore, this study establishes salinity as a key factor for causing the regulation of numerous proteins and KEGG pathways with established functions in proteostasis, immunity, and tissue remodeling. We conclude that the corresponding osmoregulatory gill proteins and KEGG pathways represent molecular phenotypes that promote transepithelial ion transport, cellular osmoregulation, and gill epithelial remodeling to adjust gill function to environmental salinity.
Surfacing and vertical behaviour of Atlantic bluefin tuna (Thunnus thynnus) in the Mediterranean Sea: implications for aerial surveys
Authors: Bauer Robert Klaus , Forget Fabien , Fromentin Jean-Marc , Capello Manuela 
Published: May 2020

Abstract
Atlantic bluefin tuna (Thunnus thynnus) (ABFT) frequently engage in surface basking and foraging behaviour that makes them detectable from afar. This behaviour is utilized for the development of fisheries-independent abundance indices based on aerial surveys, although changes in the surface-feeding dynamics of ABFT are not yet accounted for. We investigated the daytime surfacing behaviour of ABFT at different temporal and vertical resolutions based on 24 individuals (117–158 cm fork length), tagged with pop-up archival tags in the Gulf of Lion, NW-Mediterranean Sea between 2015 and 2016. The results suggest that ABFT remain usually &lt;2 min continuously within the visible surface (0–1 m) during daytime. ABFT presence in the 0–1 and 0–20 m layers varied over time and between individuals but showed a seasonal decline towards autumn with the breakdown of thermal stratification. Furthermore, the rate of surfacing events was highly correlated with the time spent in the 0–20 m layer. Geolocation estimates confirm a strong site fidelity of ABFT during the aerial survey period (August–October) in the Gulf of Lion. Our results support the choice of the survey region and period, but related indices should account for the seasonality of ABFT surface behaviour [i.e. the time spent in the 0–20 m layer.
Regional Survey of Diamondback Moth (Lepidoptera: Plutellidae) Response to Maximum Dosages of Insecticides in Georgia and Florida
Authors: Riley David , Smith Hugh , Bennett John , Torrance Philip , Huffman Evan , Sparks Alton , Gruver Charles , Dunn Thomas , Champagne Donald 
Published: May 2020

Abstract
We conducted maximum dose bioassays of insecticide for the control of diamondback moth (DBM), Plutella xylostella (Linnaeus), in cole crops, from 2016 to 2019 at several commercial locations in Georgia and Florida. The nominal maximum dose was defined as the highest labeled rate of an insecticide at the beginning of the survey in the equivalent of 935 liters/ha dilution. The results indicated low insecticide efficacy for high labeled rates of the following insecticides by common name (Insecticide Resistance Action Committee group number in parentheses). Our 4-yr survey identified very low levels of DBM larval control (&lt;47%) by lambda-cyhalothrin (3), methoxyfenozide (18), pyriproxyfen (7C), novaluron (15), bifenthrin (3), chlorantraniliprole (28), indoxacarb (22A), and methomyl (1A). The best products for DBM control (&gt;74%) listed in decreasing average levels of efficacy were naled (1B), cyclaniliprole (28), tolfenpyrad (21A), emamectin benzoate (6), and cyantraniliprole (28). Intermediate levels of control (61–71%) were obtained with Bacillus thuringiensis subspecies aizawai (11A), Bacillus thuringiensis, subsp. kurstaki, strain ABTS-351 (11A), and spinetoram (5). This rapid bioassay provided the grower with a ranking of insecticide efficacy for the control the DBM population for that farm site. These data allowed growers to make an informed decision on control quickly and plan for resistance management rotations for DBM that season.