bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soft Tissue Damage in Patients With Hemifacial Microsomia
Authors: Wang Jiaxia , Liu Enwei , Du Linna , Hu Mingyan 
Published: August 2019

Objective:
The aim of this study was to evaluate the extent of the damage to soft tissues on the affected side in patients with hemifacial microsomia (HFM).

Materials and methods:
Nine patients with HFM were included in this study and underwent computed tomography (CT) examination in the craniofacial area. The axial and coronal CT images were used for evaluating the damage to related soft tissues.

Results:
The results showed that the masseter muscle, temporal muscle, pterygoid muscles, and parotid gland were damaged on the affected side in all 9 patients with HFM. However, the extent of the damage to the pterygoid muscles was less than that to the masseter muscle, temporal muscle, and parotid gland.

Conclusions:
These findings indirectly support the crucial role of hemorrhage in the development of HFM, and the extent of damage to soft tissues may depend on the distance and barrier effect of the mandible between the hemorrhage and the affected tissues.
The Pathophysiology and Impact of Inflammation in Nonscarred Renal Interstitium: The Banff i Lesion
Authors: Nankivell Brian J. , P’Ng Chow H. , Shingde Meena , Viswanathan Seethalakshmi , Achan Anita , Renthawa Jasveen , Sharma Raghwa N. , Chapman Jeremy R. 
Published: August 2019

Background.
Interstitial inflammation (i-INT) is the driver of T-cell–mediated rejection. Its causes, pathophysiology, kinetics, and outcomes are poorly documented.

Methods.
The role of i-INT was evaluated in 2055 biopsies from 775 renal transplant recipients.

Results.
i-INT was present in 374 (18.2% prevalence) from acute and subclinical rejection (67.4%); interstitial fibrosis and tubular atrophy (14.4%); BK virus nephropathy (BKVAN) 9.9%; and acute tubular necrosis (ATN with i-INT) in 5.9% of cases. i-INT was predicted by prior T-cell–mediated rejection and BKVAN, human leukocyte antigen mismatch, cyclosporine therapy, and indication biopsy for dysfunction. It correlated with tubulitis, arteritis, and antibody markers within concurrent histology (P < 0.001). After treatment, renal functional recovery was best with histological ATN, milder i-INT, and early posttransplant biopsy times. The initial histological improvement of inflammation depended on baseline i-INT severity. Complete resolution to Banff i0 was predicted by early biopsy time, antilymphocyte therapy, recipient age, and medication compliance (all P < 0.001). Clearance i-INT was followed by delayed resolution of tubulitis (P < 0.001). i-INT was associated with histological ATN, renal dysfunction, and increased incident fibrosis on sequential pathology. Progressive fibrosis following related-rejection i-INT was dependent on tubulitis using multivariable analysis. In contrast, fibrogenesis after BKVAN or ATN was unrelated to inflammation. i-INT cases were followed by recurrent rejection in 35.3%, increased graft loss, and greater patient mortality. Multiple complementary outcome analyses determined the optimal lower diagnostic threshold for inflammation was Banff i1 score.

Conclusions.
i-INT is a heterogeneous pathological phenotype that results in adverse functional and structural outcomes, for which active and robust therapy should be considered.
Allograft and Patient Outcomes Between Indigenous and Nonindigenous Kidney Transplant Recipients
Authors: Howson Prue , Irish Ashley B. , D’Orsogna Lloyd , Chakera Aron , Swaminathan Ramyasuda , Perry Gregory , De Santis Dianne , Tolentino Raelene , Wong Germaine , Lim Wai H. 
Published: August 2019

Background.
Kidney transplant outcomes of indigenous Australians are poorer compared with nonindigenous Australians, but it is unknown whether the type of acute rejection differs between these patient groups or whether rejection mediates the effect between ethnicity, death-censored graft failure (DCGF), and death with a functioning graft (DWFG).

Methods.
Biopsy-proven acute rejection (BPAR) rates and types were compared between indigenous and nonindigenous recipients. The associations between ethnicity, BPAR, DCGF, and DWFG were examined using adjusted competing risk analyses, and mediation analysis was conducted to determine whether BPAR mediated the adverse effects between ethnicity and outcomes.

Results.
Fifty-seven (9.3%) of 616 patients who have received kidney-only transplants between 2000 and 2010 in Western Australia were indigenous. Compared with nonindigenous recipients, BPAR rates were higher in indigenous recipients (42 versus 74 episodes/100 recipients, P < 0.01), with an excess of antibody-mediated rejections. During a median follow-up of 8 years, indigenous recipients were more likely to experience BPAR, DCGF, and DWFG compared with nonindigenous recipients, with adjusted subdistribution hazard ratio of 1.94 (1.39-2.70), 1.53 (0.85-2.76; P = 0.159), and 2.14 (1.13-4.06; P = 0.020), respectively. Although 70% of the effect between ethnicity and DCGF was mediated by BPAR, no similar association was found for DWFG.

Conclusions.
Indigenous recipients experienced poorer allograft and patient outcomes compared with nonindigenous recipients, with BPAR an important determinant for DCGF. Future research identifying other risk factors and mediators associated with patient survival in indigenous recipients should be considered a priority.
Risk factors for heart failure with preserved or reduced ejection fraction among Medicare beneficiaries: Applications of competing risks analysis and gradient boosted model
Authors: Lee Moa P. , Glynn Robert J. , Schneeweiss Sebastian , Lin Kueiyu Joshua , Patorno Elisabetta , Barberio Julie , Levin Raisa , Evers Thomas , Wang Shirley V. , Desai Rishi J. 
Published: August 2019

AbstractBackgroundThe differential impact of various demographic characteristics and comorbid conditions on development of heart failure (HF) with preserved (pEF) and reduced ejection fraction (rEF) is not well studied among the elderly.Methods and ResultsUsing Medicare claims data linked to electronic health records, we conducted an observational cohort study of individuals ≥ 65 years of age without HF. A Cox proportional hazards model accounting for competing risk of HFrEF and HFpEF incidence was constructed. A gradient boosted model (GBM) assessed the relative influence (RI) of each predictor in development of HFrEF and HFpEF. Among 138,388 included individuals, 9,701 developed HF (IR= 20.9 per 1,000 person-year). Males were more likely to develop HFrEF than HFpEF (HR = 2.07, 95% CI: 1.81-2.37 vs. 1.11, 95% CI: 1.02-1.20,Pfor heterogeneity < 0.01). Atrial fibrillation and pulmonary hypertension had stronger associations with the risk of HFpEF (HR = 2.02, 95% CI: 1.80-2.26 and 1.66, 95% CI: 1.23-2.22) while cardiomyopathy and myocardial infarction were more strongly associated with HFrEF (HR = 4.37, 95% CI: 3.21-5.97 and 1.94, 95% CI: 1.23-3.07). Age was the strongest predictor across all HF subtypes with RI from GBM >35%. Atrial fibrillation was the most influential comorbidity for development of HFpEF (RI = 8.4%) while cardiomyopathy was most influential for HFrEF (RI = 20.7%).ConclusionsThese findings of heterogeneous relationships between several important risk factors and heart failure types underline the potential differences in the etiology of HFpEF and HFrEF.Key QuestionsWhat is already known about this subject?Previous epidemiologic studies describe the differences in risk factors involved in developing heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF), however, there has been no large study in an elderly population.What does this study add?This study provides further insights into the heterogeneous impact of various clinical characteristics on the risk of developing HFpEF and HFrEF in a population of elderly individuals.Employing an advanced machine learning technique allows assessing the relative importance of each risk factor on development of HFpEF and HFrEF.How might this impact on clinical practice?Our findings provide further insights into the potential differences in the etiology of HFpEF and HFrEF, which are critical in prioritizing populations for close monitoring and targeting prevention efforts.
Exploring the role of the metabolite-sensing receptor GPR109a in diabetic nephropathy
Authors: Snelson Matthew , Tan Sih Min , Higgins Gavin C. , Lindblom Runa , Coughlan Melinda T. 
Published: August 2019

AbstractAlterations in gut homeostasis may contribute to the progression of diabetic nephropathy. There has been recent attention on the renoprotective effects of metabolite-sensing receptors in chronic renal injury, including the G-protein-coupled-receptor (GPR)109a, which ligates the short chain fatty acid butyrate. However, the role of GPR109a in the development of diabetic nephropathy, a milieu of diminished microbiome-derived metabolites, has not yet been determined. This study aimed to assess the effects of insufficient GPR109a signalling via genetic deletion of GPR109a on the development of renal injury in diabetic nephropathy. Gpr109a−/− mice or their wildtype littermates (Gpr109a+/+) were rendered diabetic with streptozotocin (STZ). Mice received a control diet or an isocaloric high fiber diet (12.5% resistant starch) for 24 weeks and gastrointestinal permeability and renal injury were determined. Diabetes was associated with increased albuminuria, glomerulosclerosis and inflammation. In comparison, Gpr109a−/− mice with diabetes did not show an altered renal phenotype. Resistant starch supplementation did not afford protection from renal injury in diabetic nephropathy. Whilst diabetes was associated with alterations in intestinal morphology, intestinal permeability assessed in vivo using the FITC-dextran test was unaltered. GPR109a deletion did not worsen gastrointestinal permeability. Further, 12.5% resistant starch supplementation, at physiological concentrations, had no effect on intestinal permeability or morphology. These studies indicate that GPR109a does not play a critical role in intestinal homeostasis in a model of type 1 diabetes or in the development of diabetic nephropathy.
Effects of IgG and IgM autoantibodies on non-infected erythrocytes is related to ABO blood group in Plasmodium vivax malaria and is associated with anemia
Authors: Mourão Luiza Carvalho , Pantuzzo Medeiros Camila Maia , Cardoso-Oliveira Gustavo Pereira , Silva Roma Paula Magda da , Sultane Aboobacar Jamila da Silva , Medeiros Rodrigues Beatriz Carolina , Agero Ubirajara , Fernandes Fontes Cor Jesus , Braga Érika Martins 
Published: August 2019

AbstractAutoantibodies play an important role in the destruction of non-infected red blood cells (nRBCs) during malaria. However, the relationship between this clearance and ABO blood groups is yet to be fully enlightened, especially for Plasmodium vivax infections. Here we show that anti-RBC IgG and IgM are increased in anemic patients with acute vivax malaria. Furthermore, both antibodies are able to decrease the deformability of nRBCs, but only IgG can induce in vitro erythrophagocytosis. Such effects are enhanced in type O erythrocytes, suggesting that individuals from this blood group infected with P. vivax malaria may be more susceptible to develop anemia.
Structure-based screening of binding affinities via small-angle X-ray scattering
Authors: Chen P. , Masiewicz P. , Perez K. , Hennig J. 
Published: August 2019

ABSTRACTProtein-protein and protein-ligand interactions can alter the scattering properties of participating molecules, and thus be quantified by solution small-angle X-ray scattering (SAXS). In such cases, scattering reveals structural details of the bound complex, number of species involved, and in principle strength of the interaction. However, determining binding affinities from SAXS-based titrations is not yet an established procedure with well-defined performance expectations. We thus used periplasmic binding proteins and in particular histidine-binding protein as a standard reference, then examined precision and accuracy of affinity prediction at multiple concentrations and exposure times. By analyzing several structural and comparative scattering metrics, we found that the volatility of ratio between titrated scattering curves and a common reference most reliably quantifies ligand-triggered changes. This ratio permits the determination of affinities at low signal-to-noise ratios and without pre-determining the complex scattering, demonstrating that SAXS-based ligand screening is a promising alternative biophysical method for drug discovery pipelines.SIGNIFICANCESolution X-ray scattering can be used to screen a set of biomolecular interactions, which yields quantitative information on both structural changes and dissociation constants between binding partners. However, no common benchmarks yet exist for the application of SAXS within drug discovery workflows. Thus, investigations into its performance limitations are currently needed to make SAXS a reliable source for high-throughput screening. This study establishes a generalizable protocol based on protein-ligand interactions, and demonstrates its reproducibility across several beamline setups. In the simplest case, the micromolar binding affinities can be determined directly from measured intensities without knowledge of the molecular structure, with material consumption that is competitive with other biophysical screening techniques.
Low coverage whole genome sequencing enables accurate assessment of common variants and calculation of genome-wide polygenic scores
Authors: Homburger Julian R. , Neben Cynthia L. , Mishne Gilad , Zhou Alicia Y. , Kathiresan Sekar , Khera Amit V. 
Published: August 2019

ABSTRACTBackgroundThe inherited susceptibility of common, complex diseases may be caused by rare, ‘monogenic’ pathogenic variants or by the cumulative effect of numerous common, ‘polygenic’ variants. As such, comprehensive genome interpretation could involve two distinct genetic testing technologies -- high coverage next generation sequencing for known genes to detect pathogenic variants and a genome-wide genotyping array followed by imputation to calculate genome-wide polygenic scores (GPSs). Here we assessed the feasibility and accuracy of using low coverage whole genome sequencing (lcWGS) as an alternative to genotyping arrays to calculate GPSs.MethodsFirst, we performed downsampling and imputation of WGS data from ten individuals to assess concordance with known genotypes. Second, we assessed the correlation between GPSs for three common diseases -- coronary artery disease (CAD), breast cancer (BC), and atrial fibrillation (AF) -- calculated using lcWGS and genotyping array in 184 samples. Third, we assessed concordance of lcWGS-based genotype calls and GPS calculation in 120 individuals with known genotypes, selected to reflect diverse ancestral backgrounds. Fourth, we assessed the relationship between GPSs calculated using lcWGS and disease phenotypes in 11,502 European individuals seeking genetic testing.ResultsWe found imputation accuracy r2values of greater than 0.90 for all ten samples -- including those of African and Ashkenazi Jewish ancestry -- with lcWGS data at 0.5X. GPSs calculated using both lcWGS and genotyping array followed by imputation in 184 individuals were highly correlated for each of the three common diseases (r2= 0.93 - 0.97) with similar score distributions. Using lcWGS data from 120 individuals of diverse ancestral backgrounds, including South Asian, East Asian, and Hispanic individuals, we found similar results with respect to imputation accuracy and GPS correlations. Finally, we calculated GPSs for CAD, BC, and AF using lcWGS in 11,502 European individuals, confirming odds ratios per standard deviation increment in GPSs ranging 1.28 to 1.59, consistent with previous studies.ConclusionsHere we show that lcWGS is an alternative approach to genotyping arrays for common genetic variant assessment and GPS calculation. lcWGS provides comparable imputation accuracy while also overcoming the ascertainment bias inherent to variant selection in genotyping array design.
A flexible pipeline combining clustering and correction tools for prokaryotic and eukaryotic metabarcoding
Authors: Brandt Miriam I. , Trouche Blandine , Quintric Laure , Wincker Patrick , Poulain Julie , Arnaud-Haond Sophie 
Published: August 2019

ABSTRACTEnvironmental metabarcoding is an increasingly popular tool for studying biodiversity in marine and terrestrial biomes. With sequencing costs decreasing, multiple-marker metabarcoding, spanning several branches of the tree of life, is becoming more accessible. However, bioinformatic approaches need to adjust to the diversity of taxonomic compartments targeted as well as to each barcode gene specificities. We built and tested a pipeline based on Illumina read correction with DADA2 allowing analyzing metabarcoding data from prokaryotic (16S) and eukaryotic (18S, COI) life compartments. We implemented the option to cluster Amplicon Sequence Variants (ASVs) into Operational Taxonomic Units (OTUs) with swarm v2, a network-based clustering algorithm, and to further curate the ASVs/OTUs based on sequence similarity and co-occurrence rates using a recently developed algorithm, LULU. Finally, flexible taxonomic assignment was implemented via Ribosomal Database Project (RDP) Bayesian classifier and BLAST. We validate this pipeline with ribosomal and mitochondrial markers using eukaryotic mock communities and 42 deep-sea sediment samples. The results show that ASVs, reflecting genetic diversity, may not be appropriate for alpha diversity estimation of organisms fitting the biological species concept. The results underline the advantages of clustering and LULU-curation for producing more reliable metazoan biodiversity inventories, and show that LULU is an effective tool for filtering metazoan molecular clusters, although the minimum identity threshold applied to co-occurring OTUs has to be increased for 18S. The comparison of BLAST and the RDP Classifier underlined the potential of the latter to deliver very good assignments, but highlighted the need for a concerted effort to build comprehensive, ecosystem-specific, databases adapted to the studied communities.
Temperature, photoperiod and life history traits inDrosophila subobscura
Authors: MacLean Heidi J. , Gilchrist George W. 
Published: August 2019

AbstractTemperature and photoperiod are generally reliable indicators of seasonality that have shaped the life histories of many temperate zone organisms. Anthropogenic climate change, however, may alter historical weather patterns and seasonal cues. Many studies have evaluated thermal effects on life history traits, but fewer have also examined photoperiodic effects. Because the degree of seasonal cue varies across latitude, we examine developmental plasticity inDrosophila subobscurapopulations sampled from latitudinal clines across Europe and North America. We examine the interaction between temperature and photoperiod on insect development time, adult survival, and fitness using a two by two factorial design with long (16L:8D) and short days (8L:16D) at high (23°C) and low temperatures (15°C).. We find that development time is dependent on both temperature and photoperiod but the low temperature/long day treatment revealed a dramatic and unexpected 4.5 day delay in eclosion. Fitness, estimated by the intrinsic rate of increase (r), showed a significant increase in response to temperature and a decrease in response to day length, and an interaction such that long-days reduced the effects of temperature. Additionally, cooler temperatures increased lifespan, and long-days reduced survivorship; temperature and day length interacted such that lifespan is relatively shorter in seasonally mismatched (long-cool, short-warm) conditions compared to matched conditions. These data highlight the importance of multiple abiotic factors in predicting species’ responses to climate change.
The role and robustness of the Gini coefficient as an unbiased tool for the selection of Gini genes for normalising expression profiling data
Authors: Muelas Marina Wright , Mughal Farah , O’Hagan Steve , Day Philip J. , Kell Douglas B. 
Published: August 2019

AbstractWe recently introduced the Gini coefficient (GC) for assessing the expression variation of a particular gene in a dataset, as a means of selecting improved reference genes over the cohort (‘housekeeping genes’) typically used for normalisation in expression profiling studies. Those genes (transcripts) that we determined to be useable as reference genes differed greatly from previous suggestions based on hypothesis-driven approaches. A limitation of this initial study is that a single (albeit large) dataset was employed for both tissues and cell lines.We here extend this analysis to encompass seven other large datasets. Although their absolute values differ a little, the Gini values and median expression levels of the various genes are well correlated with each other between the various cell line datasets, implying that our original choice of the more ubiquitously expressed low-Gini-coefficient genes was indeed sound. In tissues, the Gini values and median expression levels of genes showed a greater variation, with the GC of genes changing with the number and types of tissues in the data sets. In all data sets, regardless of whether this was derived from tissues or cell lines, we also show that the GC is a robust measure of gene expression stability. Using the GC as a measure of expression stability we illustrate its utility to find tissue- and cell line-optimised housekeeping genes without any prior bias, that again include only a small number of previously reported housekeeping genes. We also independently confirmed this experimentally using RT-qPCR with 40 candidate GC genes in a panel of 10 cell lines. These were termed the Gini Genes.In many cases, the variation in the expression levels of classical reference genes is really quite huge (e.g. 44 fold for GAPDH in one data set), suggesting that the cure (of using them as normalising genes) may in some cases be worse than the disease (of not doing so). We recommend the present data-driven approach for the selection of reference genes by using the easy-to-calculate and robust GC.
Mesolimbic dopamine D2 receptors and neural representations of subjective value
Authors: Castrellon Jaime J. , Young Jacob S. , Dang Linh C. , Cowan Ronald L. , Zald David H. , Samanez-Larkin Gregory R. 
Published: August 2019

AbstractThe process by which the value of delayed rewards is discounted varies from person to person. It has been suggested that these individual differences in subjective valuation of delayed rewards are supported by mesolimbic dopamine D2-like receptors (D2Rs) in the ventral striatum. However, no study to date has documented an association between direct measures of dopamine receptors and neural representations of subjective value in humans. Here, we examined whether individual differences in D2R availability were related to neural subjective value signals during decision making. Human participants completed a monetary delay discounting task during an fMRI scan and on a separate visit completed a PET scan with the high affinity D2R tracer [18F]fallypride. Region-of-interest analyses revealed that D2R availability in the ventral striatum was positively correlated with subjective value-related activity in the ventromedial prefrontal cortex and midbrain but not with choice behavior. Whole-brain analyses revealed a positive correlation between ventral striatum D2R availability and subjective value-related activity in the left inferior frontal gyrus. These findings are the first to identify a link between directly-measured mesolimbic dopamine function and subjective value representation in humans and suggest a mechanism by which individuals vary in neural representation of discounted subjective value.