bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of the Breast Cancer Provider Discussion Law on Breast Reconstruction Rates in New York State
Authors: Fu Rose H. , Baser Onur , Li Lu , Kurlansky Paul , Means Jessica , Rohde Christine H. 
Published: June 2019

Background:
New York State passed the Breast Cancer Provider Discussion Law in 2010, mandating discussion of insurance coverage for reconstruction and expedient plastic surgical referral, two significant factors found to affect reconstruction rates. This study examines the impact of this law.

Methods:
A retrospective cohort study of the New York State Planning and Research Cooperative System database to examine breast reconstruction rates 3 years before and 3 years after law enactment was performed. Difference-interrupted time series models were used to compare trends in the reconstruction rates by sociodemographic factors and provider types.

Results:
The study included 32,452 patients. The number of mastectomies decreased from 6479 in 2008 to 5235 in 2013; the rate of reconstruction increased from 49 percent in 2008 to 62 percent in 2013. This rise was seen across all median income brackets, races, and age groups. When comparing before to after law enactment, the increase in risk-adjusted reconstruction rates was significantly higher for African Americans and elderly patients, but the disparity in reconstruction rates did not change for other races, different income levels, or insurance types. Reconstruction rates were also not significantly different between those treated in various hospital settings.

Conclusions:
The aim of the Breast Cancer Provider Discussion Law is to improve reconstruction rates through provider-driven patient education. The authors’ data show significant change following law passage in African American and elderly populations, suggesting effectiveness of the law. The New York State Provider Discussion Law may provide a template for other states to model legislation geared toward patient-centered improvement of health outcomes.
Adipose-Derived Stem Cells and Ceiling Culture-Derived Preadipocytes Cultured from Subcutaneous Fat Tissue Differ in Their Epigenetic Characteristics and Osteogenic Potential
Authors: Sasahara Yoshitaro , Kubota Yoshitaka , Kosaka Kentaro , Adachi Naoki , Yamaji Yoshihisa , Nagano Hidekazu , Akita Shinsuke , Kuroda Masayuki , Tanaka Tomoaki , Bujo Hideaki , Mitsukawa Nobuyuki 
Published: June 2019

Background:
Adipose-derived stem cells and ceiling culture-derived preadipocytes can be harvested from subcutaneous adipose tissue. Little is known about the epigenetic differences, which may contribute to differences in osteogenic potential, between these cell types. The purpose of this study was to address the osteogenic potential and underlying epigenetic status of adipose-derived stem cells and ceiling culture-derived preadipocytes.

Methods:
Adipose-derived stem cells and ceiling culture-derived preadipocytes were cultured from abdominal subcutaneous fat tissues of four metabolically healthy, lean female patients. After 7 weeks of culture, cellular responses to osteogenic differentiation media were examined. To evaluate the osteogenic potentials of undifferentiated adipose-derived stem cells and ceiling culture-derived preadipocytes, two types of epigenetic assessment were performed using next-generation sequencing: DNA methylation assays with the Human Methylation 450K BeadChip, and chromatin immunoprecipitation assays for trimethylation of histone H3 at lysine 4.

Results:
Human ceiling culture-derived preadipocytes showed greater osteogenic differentiation ability than did adipose-derived stem cells. In an epigenetic survey of the promoters of four osteogenic regulator genes (RUNX2, SP7, ATF4, and BGLAP), the authors found a general trend toward decreased CpG methylation and increased trimethylation of histone H3 at lysine 4 levels in ceiling culture-derived preadipocytes as compared to adipose-derived stem cells, indicating that these genes were more likely to be highly expressed in ceiling culture-derived preadipocytes.

Conclusions:
The surveyed epigenetic differences between adipose-derived stem cells and ceiling culture-derived preadipocytes were consistent with the observed differences in osteogenic potential. These results enhance the authors’ understanding of these cells and will facilitate their further application in regenerative medicine.
Brief Report: Markers of Spontaneous Preterm Delivery in Women Living With HIV: Relationship With Protease Inhibitors and Vitamin D
Authors: Weinberg Adriana , Huo Yanling , Kacanek Deborah , Patel Kunjal , Watts D. Heather , Wara Diane , Hoffman Risa M. , Klawitter Jelena , Christians Uwe ,   for IMPAACT P1025 Team
Published: June 2019

Background:
Women living with HIV (WLHIV) have increased risk of spontaneous preterm delivery (SPTD). We sought to identify plasma predictors of SPTD and their correlations with factors that increase the risk of SPTD, such as vitamin D deficiency and use of protease inhibitors.

Design:
Plasma was obtained from 103 WLHIV with SPTD (≤35 weeks gestation) and 205 controls with term deliveries (TDs; ≥37 weeds) matched to cases 2:1 by race and gestational age at blood draw. TNFα, IFNγ, IL6, IL8, IL1β, IL18, IL17, granulocyte colony stimulating factor (GCSF), MCP1, IP10, sIL2Rα, sCD14, vascular endothelial factor a, monocyte colony stimulation factor, GROα, MMP9, IL10, TGFβ, sCTLA4, and eicosanoids were compared between cases adjusting for known SPTD risk factors.

Results:
Participants had similar demographic characteristics, but cases had higher plasma HIV RNA, lower CD4 cells, and more advanced HIV disease compared with controls. High sIL2Rα was associated with increased risk of SPTD. High sCD14, GCSF, PGF2α, and 5-HEPE were marginally associated with increased risk of SPTD. Women who initiated protease inhibitors-containing antiretroviral treatment before or during the first trimester had higher levels of GCSF and 5-HEPE compared with women without such exposure before plasma collection. Vitamin D insufficiency was associated with higher inflammatory sCD14 and PGF2α, and lower anti-inflammatory 5-HEPE.

Conclusions:
The best plasma predictor of SPTD in WLHIV was sIL2Rα, a marker of T-cell activation. Markers of monocyte activation and eicosanoids were marginally increased in WLHIV and SPTD, suggesting that they may also play a role in the pathogenesis of this disorder.
Predicting Synthetic Lethal Interactions using Heterogeneous Data Sources
Authors: Liany Herty , Jeyasekharan Anand , Rajan Vaibhav 
Published: June 2019

AbstractMotivationA synthetic lethal (SL) interaction is a relationship between two functional entities where the loss of either one of the entities is viable but the loss of both entities is lethal to the cell. Such pairs can be used as drug targets in targeted anticancer therapies, and so, many methods have been developed to identify potential candidate SL pairs. However, these methods use only a subset of available data from multiple platforms, at genomic, epigenomic and transcriptomic levels; and hence are limited in their ability to learn from complex associations in heterogeneous data sources.ResultsIn this paper we develop techniques that can seamlessly integrate multiple heterogeneous data sources to predict SL interactions. Our approach obtains latent representations by collective matrix factorization based techniques, which in turn are used for prediction through matrix completion. Our experiments, on a variety of biological datasets, illustrate the efficacy and versatility of our approach, that outperforms state-of-the-art methods for predicting SL interactions and can be used with heterogeneous data sources with minimal feature engineering.AvailabilitySoftware available athttps://github.com/lianyhContactvaibhav.rajan@nus.edu.sg
Targeted Clinical Metabolomics Platform for the Stratification of Diabetic Patients
Authors: Ahonen Linda , Jäntti Sirkku , Suvitaival Tommi , Theilade Simone , Risz Claudia , Kostiainen Risto , Rossing Peter , Orešič Matej , Hyötyläinen Tuulia 
Published: June 2019

AbstractBackgroundSeveral small molecule biomarkers have been reported in the literature for prediction and diagnosis of (pre)diabetes, its co-morbidities and complications. Here, we report the development and validation of a novel, quantitative, analytical method for use in the diabetes clinic. This method enables the determination of a selected panel of 36 metabolite biomarkers from human plasma.MethodsBased on a review of the literature and our own data, we selected a panel of metabolites indicative of various clinically-relevant pathogenic stages of diabetes. We combined these candidate biomarkers into a single ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method and optimized it, prioritizing simplicity of sample preparation and time needed for analysis, enabling high-throughput analysis in clinical laboratory settings.ResultsWe validated the method in terms of limit of (a) detection (LOD), (b) limit of quantitation (LOQ), (c) linearity (R2), (d) linear range, and (e) intra- and inter-day repeatability of each metabolite. The method’s performance was demonstrated in the analysis of selected samples from a diabetes cohort study. Metabolite levels were associated with clinical measurements and kidney complications in type 1 diabetes (T1D) patients. Specifically, both amino acids and amino acid-related analytes were associated with macro-albuminuria. Additionally, specific bile acids were associated with kidney function, anti-hypertensive medication, statin medication and clinical lipid measurements.ConclusionsThe developed analytical method is suitable for robust determination of selected plasma metabolites in the diabetes clinic.
Improved control of Septoria tritici blotch in durum wheat using cultivar mixtures
Authors: Ben M’Barek S. , Karisto P. , Abdedayem W. , Laribi M. , Fakhfakh M. , Kouki H. , Mikaberidze A. , Yahyaoui A. 
Published: June 2019

AbstractMixtures of cultivars with contrasting levels of resistance can suppress infectious diseases in wheat, as demonstrated in numerous field experiments. Most studies focused on airborne pathogens in bread wheat, while splash-dispersed pathogens have received less attention, and no studies have been conducted in durum wheat. We conducted a two-year field experiment in Tunisia, to evaluate the performance of cultivar mixtures with varying proportions of resistance (0–100%) in controlling the polycyclic, splash-dispersed disease Septoria tritici blotch (STB) in durum wheat. To measure STB severity, we used a high-throughput method based on digital image analysis of 3074 infected leaves collected from 42 and 40 experimental plots during the first and second years, respectively. This allowed us to quantify pathogen reproduction on wheat leaves and to acquire a large dataset that exceeds previous studies with respect to accuracy and precision. Our analyses show that introducing only 25% of a disease-resistant cultivar into a pure stand of a susceptible cultivar provides a substantial reduction of almost 50% in disease severity compared to the susceptible pure stand. However, comprising the resistant component of two cultivars instead of one did not further improve disease control, contrary to predictions of epidemiological theory. Susceptible cultivars can be agronomically superior to resistant cultivars or be better accepted by growers for other reasons. Hence, if mixtures with only a moderate proportion of the resistant cultivar provide a similar degree of disease control as resistant pure stands, as our analysis indicates, such mixtures are more likely to be accepted by growers.
High and asymmetric somato-dendritic coupling of V1 layer 5 neurons independent of visual stimulation and locomotion
Authors: Francioni Valerio , Padamsey Zahid , Rochefort Nathalie L. 
Published: June 2019

AbstractActive dendrites impact sensory processing and behaviour. However, it remains unclear how active dendritic integration relates to somatic output in vivo. We imaged semi-simultaneously GCaMP6s signals in the soma, trunk and distal tuft dendrites of layer 5 pyramidal neurons in the awake mouse primary visual cortex. We found that apical tuft signals were dominated by widespread, highly correlated calcium transients throughout the tuft. While these signals were highly coupled to trunk and somatic transients, the frequency of calcium transients was found to decrease in a distance-dependent manner from soma to tuft. Ex vivo recordings suggest that low-frequency back-propagating action potentials underlie the distance-dependent loss of signals, while coupled somato-dendritic signals can be triggered by high-frequency somatic bursts or strong apical tuft depolarization. Visual stimulation and locomotion increased neuronal activity without affecting somato-dendritic coupling. High, asymmetric somato-dendritic coupling is therefore a widespread feature of layer 5 neurons activity in vivo.
Absence of Replication fork associated factor CTF4 and F-box motif Encoding Gene SAF1 leads to reduction in Cell Size and Stress Tolerance Phenotype inS. cerevisiae
Authors: Sharma Meenu , Singh Samar , Verma V. , Bairwa Narendra K 
Published: June 2019

AbstractChromosome transmission fidelity factor, Ctf4 inS. cerevisiaeassociates with replication fork and helps in the sister chromatid cohesion. At the replication fork, Ctf4 links DNA helicase with the DNA polymerase. The absence of Ctf4 invokes replication checkpoint in the cells. The Saf1 ofS.cerevisiaeinteracts with Skp1 of SCF-E3 ligase though F box-motif and ubiquitinates the adenine deaminase Aah1 during phase transition due to nutrient stress. The genetic interaction between the CTF4 and SAF1 has not been studied. Here we report genetic interaction between CTF4 and SAF1 which impacts the growth fitness and response to stress. The single and double gene deletions of SAF1 and CTF4 were constructed in the BY4741 genetic background. The strains were tested for growth on rich media and media containing stress causing agents. Thesaf1Δctf4Δ cells with reduced cell size showed the fastest growth phenotype on YPD medium when compared with thesaf1Δ,ctf4Δ,and WT. Thesaf1Δctf4Δ cells also showed the tolerance to MMS, NaCl, Glycerol, SDS, Calcofluor white, H2O2, DMSO, Benomyl, and Nocodazole when compared with the saf1Δ,ctf4Δ, and WT cells. However,saf1Δctf4Δ cells showed the sensitivity to HU when compared with WT andsaf1Δ. Based on these observations we suggest that SAF1 and CTF4 interact genetically to regulate the cell size, growth and stress response.
Revealing microbial assemblage structure in the human gut microbiome using latent Dirichlet allocation
Authors: Hosoda Shion , Nishijima Suguru , Fukunaga Tsukasa , Hattori Masahira , Hamada Michiaki 
Published: June 2019

AbstractRecent research has revealed that there are various microbial species in the human gut microbiome. To clarify the structure of the human gut microbiome, many data mining methods have been applied to microbial composition data. Cluster analysis, one of the key data mining methods that have been used in human gut microbiome research, can classify the human gut microbiome into three clusters, called enterotypes. The human gut microbiome has been suggested to be composed of the microbial assemblages or groups of co-occurring microbes, and one human gut microbiome can contain several microbial assemblages. However, cluster analysis can cluster samples into groups without capturing minor assemblages. In addition, a reliable method of assemblage detection has not been established, and little is known about the distributions of microbial assemblages at a population-level scale. Accordingly, the purpose of this study was to clarify the microbial assemblages in the human gut microbiome. In this study, we detected gut microbiome assemblages using a latent Dirichlet allocation (LDA) method, which was first proposed for the classification of documents in natural language processing. We applied LDA to a large-scale human gut metagenome dataset and found that a four-assemblage LDA model can represent relationships between enterotypes and assemblages with high interpretability. This model indicates that each individual tends to have several assemblages, and each of three assemblages corresponded to each enterotype. However, the C-assemblage can exist in all enterotypes. Interestingly, the dominant genera of the C-assemblage (Clostridium, Eubacterium, Faecalibacterium, Roseburia, Coprococcus, and Butyrivibrio) included butyrate-producing species such as Faecalibacterium prausnitzii. Finally, we revealed that genera mainly appearing in the same assemblage were correlated to each other. We conducted an assemblage analysis on a large-scale human gut metagenome dataset using LDA, a powerful method for detection of microbial assemblages. This approach has the potential to reveal the structure of the human gut microbiome.
The mechanical stability of the world’s tallest broadleaf trees
Authors: Jackson T. , Shenkin A. , Majalap N. , bin Jami J. , bin Sailim A. , Reynolds G. , Coomes D.A. , Chandler C.J. , Boyd D.S. , Burt A. , Wilkes Phil , Disney M. , Malhi Y. 
Published: June 2019

AbstractThe factors that limit the maximum height of trees, whether ecophysiological or mechanical, are the subject of longstanding debate. Here we examine the role of mechanical stability in limiting tree height and focus on trees from the tallest tropical forests on Earth, in Sabah, Malaysian Borneo, including the recently discovered tallest tropical tree, a 100.8 mShorea faguetiana. We use terrestrial laser scans,in situstrain gauge data and finite-element simulations to map the architecture of tall broadleaf trees and monitor their response to wind loading. We demonstrate that a tree’s risk of breaking due to gravity or self-weight decreases with tree height and is much more strongly affected by tree architecture than by material properties. In contrast, wind damage risk increases with tree height despite the larger diameters of tall trees, resulting in a U-shaped curve of mechanical risk with tree height. The relative rarity of extreme wind speeds in north Borneo may be the reason it is home to the tallest trees in the tropics.
Illuminating the functional rare biosphere of the Greenland Ice Sheet’s Dark Zone
Authors: Gokul Jarishma K. , Cameron Karen A. , Irvine-Fynn Tristram D.L. , Cook Joseph M. , Hubbard Alun , Stibal Marek , Hegarty Matt , Mur Luis A.J. , Edwards Arwyn 
Published: June 2019

AbstractThe Dark Zone of the western Greenland Ice Sheet is the most expansive region of contiguous bare terrestrial ice in the Northern Hemisphere. Microbial processes within the Dark Zone play an important role in driving extensive albedo reduction and amplified melting, yet the composition and function of those consortia have not been fully identified. Here we present the first results from joint 16S rRNA gene and 16S rRNA (cDNA) analysis for the comparison of input (snow), storage (cryoconite), and output (supraglacial stream water) habitats across the Dark Zone over the melt season. Our analysis reveals that all three Dark Zone communities are characterized by a preponderance of rare taxa exhibiting high protein synthesis potential (PSP). Furthermore, taxa with high PSP represent highly connected “bottlenecks” within community structure, consistent with roles as metabolic hubs within their communities. Finally, the detection of low abundance-high PSP taxa affiliated withMethylobacteriumwithin snow and stream water indicates a potential role forMethylobacteriumin the carbon cycle of Greenlandic snowpacks, and importantly, the export of potentially active methylotrophs to the bed of the Greenland Ice Sheet. By comparing the dynamics of bulk and potentially active microbial communities in the Dark Zone of the Greenland Ice Sheet our study provides insight into the mechanisms and impacts of the microbial colonization of this critical region of our melting planet.
A case for a reverse-frame coding sequence in a group of positive-sense RNA viruses
Authors: Dinan Adam M. , Lukhovitskaya Nina I. , Olendraite Ingrida , Firth Andrew E. 
Published: June 2019

ABSTRACTPositive-sense single-stranded RNA viruses form the largest and most diverse group of eukaryote-infecting viruses. Their genomes comprise one or more segments of coding-sense RNA that function directly as messenger RNAs upon release into the cytoplasm of infected cells. Positive-sense RNA viruses are generally accepted to encode proteins solely on the positive strand. However, we previously identified a surprisingly long (~1000 codons) open reading frame (ORF) on the negative strand of some members of the familyNarnaviridaewhich, together with RNA bacteriophages of the familyLeviviridae, form a sister group to all other positive-sense RNA viruses. Here, we completed the genomes of three mosquito-associated narnaviruses, all of which have the long reverse-frame ORF. We systematically identified narnaviral sequences in public data sets from a wide range of sources, including arthropod, fungi and plant transcriptomic datasets. Long reverse-frame ORFs are widespread in one clade of narnaviruses, where they frequently occupy >95% of the genome. The reverse-frame ORFs correspond to a specific avoidance of CUA, UUA and UCA codons (i.e. stop codon reverse complements) in the forward-frame RNA-dependent RNA polymerase ORF. However, absence of these codons cannot be explained by other factors such as inability to decode these codons or GC3 bias. Together with other analyses, we provide the strongest evidence yet of coding capacity on the negative strand of a positive-sense RNA virus. As these ORFs comprise some of the longest known overlapping genes, their study may be of broad relevance to understanding overlapping gene evolution andde novoorigin of genes.
HAT1 drives a gene-metabolite circuit that links nutrient metabolism to histone production
Authors: Gruber Joshua J. , Geller Benjamin , Lipchik Andrew M. , Chen Justin , Salahudeen Ameen A. , Ram Ashwin N. , Ford James M. , Kuo Calvin J. , Snyder Michael P. 
Published: June 2019

SummaryThe energetic costs of duplicating chromatin along with DNA replication are large and therefore likely depend on nutrient sensing checkpoints and metabolic inputs. By studying chromatin modifiers regulated by epithelial growth factor, we identify histone acetyltransferase 1 (HAT1) as an induced gene that enhances cell proliferation by coordinating histone production with glucose metabolism. In addition to its canonical role as a cytoplasmic free histone H4 acetyltransferase, a HAT1-containing complex binds specifically at promoters of H4 genes. HAT1 stimulated acetate delivery and consumption at H4 promoters to drive S-phase H4 transcription. This required the presence of a histone H4-specific promoter element in the region of HAT1 chromatin binding. These data describe a feed-forward circuit whereby HAT1-dependent capture of acetyl-groups drives further H4 production to support growth-factor dependent proliferation. These findings also extend to human disease and animal models, as high HAT1 levels associate with poor outcomes across multiple cancer types.