bluuebunny/crossref_metadata_2025_split huggingface dataset:
Podocytopathy in the mesangial proliferative immunoglobulin A nephropathy: new insights into the mechanisms of damage and progression
Authors: Trimarchi Hernán , Coppo Rosanna 
Published: December 2018

Abstract
Immunoglobulin A nephropathy (IgAN) was defined as a mesangiopathic disease, since the primary site of deposition of IgA immune material is the mesangium, and proliferation of mesangial cells and matrix excess deposition are the first histopathologic lesions. However, the relentless silent progression of IgAN is mostly due to the development of persistent proteinuria, and recent studies indicate that a major role is played by previous damage of function and anatomy of podocytes. In IgAN, the podocytopathic changes are the consequence of initial alterations in the mesangial area with accumulation of IgA containing immune material. Podocytes are therefore affected by interactions of messages originally driven from the mesangium. After continuous insult, podocytes detach from the glomerular basement membrane. This podocytopathy favours not only the development of glomerular focal and segmental sclerosis, but also the progressive renal function loss. It is still debated whether these lesions can be prevented or cured by corticosteroid/immunosuppressive treatment. We aimed to review recent data on the mechanisms implicated in the podocytopathy present in IgAN, showing new molecular risk factors for progression of this disease. Moreover, these observations may indicate that the target for new drugs is not only focused on decreasing the activity of mesangial cells and inflammatory reactions in IgAN, but also on improving podocyte function and survival.
Prospective Evaluation of Multinational Association of Supportive Care in Cancer Risk Index Score for Gynecologic Oncology Patients With Febrile Neutropenia
Authors: Gunderson Camille C. , Erickson Britt K. , Wilkinson-Ryan Ivy , Vesely Sara K. , Leath Charles A. , Gehrig Paola A. , Moore Kathleen N. 
Published: December 2018

Background:
The Multinational Association of Supportive Care of Cancer (MASCC) risk-index score has been validated as a stratification tool for febrile neutropenia (FN) risk in a heterogeneous group of cancer patients; recently, it has been deemed a suitable tool in gynecologic oncology patients in a retrospective study. This is a prospective multi-institutional study wherein we sought to validate MASCC score for stratifying FN morbidity in gynecologic oncology patients.

Methods:
IRB approval was obtained at 4 institutions for prospective data collection of gynecologic cancer patients admitted with FN from 3/1/2013 to 9/1/2014. Participating institutions have a policy of inpatient management of FN patients receiving chemotherapy. Deidentified data was compiled and processed at the leading institution.

Results:
In total, 31 patients met inclusion criteria. Most had advanced stage disease (67%). 100% of patients were receiving chemotherapy (57% for primary, 43% for recurrent disease). 55% had a positive culture. Median MASCC score was 21 (range, 10 to 26); 58% of patients were considered low risk. High risk patients more often had one (11% vs. 38%, P=0.09) or multiple (6% vs. 23%, P=0.28) severe complications, ICU admission (0% vs. 15%, P=0.17), and delay in next chemotherapy cycle (33% vs. 54%, P=0.25). No patients died from FN during the study period.

Conclusions:
This pilot data suggests that MASCC score may be a promising tool for determining suitability of outpatient management of FN in gynecologic oncology patients. Larger studies are warranted to achieve statistically significant results, which may enable us to effectively utilize this risk stratification tool for cost containment and avoidance of nosocomial infections.
DETERMINING THE EFFECT OF DIABETES DURATION ON RETINAL AND CHOROIDAL THICKNESSES IN CHILDREN WITH TYPE 1 DIABETES MELLITUS
Authors: Niestrata-Ortiz Magdalena , Fichna Piotr , Stankiewicz Witold , Stopa Marcin 
Published: December 2018

Purpose:
Determining the effect of diabetes mellitus duration on retinal and choroidal thicknesses in children with Type 1 diabetes mellitus (T1DM).

Methods:
Children (aged 6–18 years) with Type 1 diabetes and no diabetic retinopathy and age-matched controls were examined using Topcon spectral domain optical coherence tomography. Choroidal thickness and retinal thickness in macula area were measured. The study group was divided into 3 subgroups depending on diabetes mellitus duration—Group 1: <5 years (n = 52), Group 2: 5 to 10 years (n = 39), and Group 3: >10 years (n = 30).

Results:
One hundred and twenty-one diabetic children and 32 controls were included. The central choroidal thickness increased from 305.5 μm (SD: 61.7 μm) in the control group to 309.2 μm (SD: 70.1 μm) in Group 1, 315.2 μm (SD: 64.3 μm) in Group 2, and 367.4 μm (SD: 66.0 μm) in Group 3. Group 3 differed significantly from Group 1 (P = 0.0002), Group 2 (P = 0.0014), and the control group (P = 0.0003). The choroid-to-retina thickness ratio was lowest in controls, 1.01 (SD: 0.17), and highest in Group 3, 1.21 (SD: 0.2). Group 3 differed significantly from Group 1, Group 2, and the control group with P = 0.0002, P = 0.0014, and P = 0.0001, respectively. No retina thickening was found.

Conclusion:
Changes in the choroid may occur before the development of diabetic retinopathy and seem to progress with increasing diabetes mellitus duration despite the absence of diabetic retinopathy and without associated retina thickening. Choroidal thickness could be valuable for screening in diabetic children.
Risk Factors Associated With Upper Aerodigestive Tract or Coliform Bacterial Overgrowth of the Small Intestine in Symptomatic Patients
Authors: Bohm Matthew , Shin Andrea , Teagarden Sean , Xu Huiping , Gupta Anita , Siwiec Robert , Nelson David , Wo John M. 
Published: December 2018

Introduction:
The clinical relevance of bacterial types identified in small bowel aspirate cultures during diagnostic evaluation of small intestinal bacterial overgrowth (SIBO) is unclear.

Aim:
The main purpose of this study was to assess associations between risk factors for upper aerodigestive tract (UAT) or coliform SIBO and SIBO diagnosis by culture.

Materials and Methods:
Small bowel aspirates were cultured in patients with suspected SIBO, defined as ≥104 colony-forming units/mL coliform or ≥105 colony-forming units/mL UAT bacteria. History was reviewed for risk factors and potential SIBO complications. Symptoms, quality of life, psychological traits, and laboratory values were assessed. We compared groups by 2-sample t test, Wilcoxon rank sum test, and the Fisher exact test. Overall associations of primary and secondary endpoints with type of bacterial overgrowth were assessed by analysis of variance F-test, Kruskal-Wallis test, and the Fisher exact tests. Associations of risk factors with type of overgrowth were explored using multinomial logistic regression.

Results:
Among 76 patients, 37 had SIBO (68% coliform, 33% UAT) and 39 did not. Conditions (P=0.02) and surgery (P<0.01) associated with decreased gastric acid were associated with SIBO. In multinomial logistic regression, conditions of decreased acid was associated with UAT SIBO [odds ratio (OR), 5.8; 95% confidence interval, 1.4-33.3]. Surgery causing decreased acid was associated with UAT [OR, 9.5 (1.4-106)] and coliform SIBO [OR, 8.4 (1.6-86.4)]. Three patients with discontinuous small bowel had coliform SIBO [OR, 17.4 (1.2-2515)]. There were no differences in complications, overall symptoms, quality of life, or psychological traits.

Conclusions:
Conditions or surgeries associated with decreased gastric acid are associated with SIBO diagnosis by culture.
Risk and Protective Factors Related to Early Adverse Life Events in Irritable Bowel Syndrome
Authors: Ju Tiffany , Naliboff Bruce D. , Shih Wendy , Presson Angela P. , Liu Cathy , Gupta Arpana , Mayer Emeran A. , Chang Lin 
Published: December 2018

Background:
Irritable bowel syndrome (IBS) is a stress-sensitive disorder of brain-gut interactions associated with a higher prevalence of early adverse life events (EALs). However, it is incompletely understood how trauma severity or disclosure influence the risk of developing IBS or symptom severity.

Aims:
To determine whether (1) IBS patients report a greater number of EALs compared with healthy controls; (2) trauma severity and first age of EAL increase the odds of IBS; (3) confiding in others reduces the odds of IBS; (4) the number, trauma severity, and first age of EAL are associated with symptom severity; (5) sex differences exist.

Methods:
In total, 197 IBS patients (72% women, mean age=30.28 y) and 165 healthy controls (59% women, mean age=30.77 y) completed the Childhood Traumatic Events Scale, measuring severity of EALs and degree of confiding in others. Regression analyses were used to predict IBS status from EALs and association between gastrointestinal symptoms and EALs.

Results:
A greater number of EALs [odds ratio (OR)=1.36, 95% confidence interval (CI), 1.14-1.62; P<0.001] and higher perceived trauma severity (OR=1.13, 95% CI, 1.08-1.19; P<0.001) were associated with increased odds of IBS. Confiding in others decreased the odds of having IBS (OR=0.83, 95% CI, 0.72-0.96; P=0.012). The first age of EAL was not predictive of IBS. No sex differences were found.

Conclusions:
Assessing the traumatic severity of EALs and amount of confiding in others is important as they can affect the risk of having IBS. Our findings emphasize early intervention to improve health outcomes in individuals with EALs.
Quantitative Hepatitis B Surface Antigen Predicts Hepatitis B Transmission in Infants Born to e Antigen–positive Mothers
Authors: Peng Songxu , Wan Zhihua , Liu Tingting , Wang Yanni , Chen Hongyan , Li Xiu , Du Yukai 
Published: December 2018

Goals:
This study aimed to explore whether quantitative surface antigen [hepatitis B surface antigen (HBsAg)] can be used as a surrogate marker of hepatitis B virus (HBV) DNA to predict hepatitis B transmission before the first hepatitis vaccine dose in infants born to hepatitis B e antigen (HBeAg)-positive pregnant women.

Background:
Currently, HBV transmission persistently occurs worldwide, especially in infants born to e antigen (HBeAg)-positive highly viremic mothers. However, due to high cost, the extensive use of viral load testing to identify these high-risk mothers is limited.

Materials and Methods:
In total of 275 HBeAg-positive pregnant women paired with 280 infants were enrolled in this study. Quantitative HBsAg and HBV DNA levels were measured in the third trimester. Spearman rank correlation was used to assess the correlation between HBsAg levels and viral load, and multivariate logistic regression to identify factors related to HBV transmission in infants.

Results:
Among 280 infants included, 15 (5.4%) infants were infected with HBV. In this study, we observed that quantitative HBsAg was positively correlated with maternal viral load (r=0.70, P<0.001) and highly predicted HBV transmission in infants born to HBeAg-positive mothers with area under the curve of 0.76 (95% confidence interval, 0.71-0.81). The optimum threshold HBsAg levels above 4.6 log10 IU/mL to predict HBV transmission in infants had a sensitivity of 80.0%, specificity of 67.9%.

Conclusions:
Quantitative HBsAg could be used as a surrogate marker of HBV DNA levels to predict hepatitis B transmission occurring before the injection of first-dose vaccine in infants born to e antigen–positive mothers.
Violating the normality assumption may be the lesser of two evils
Authors: Knief Ulrich , Forstmeier Wolfgang 
Published: December 2018

AbstractWhen data are not normally distributed (e.g. skewed, zero-inflated, binomial, or count data) researchers are often uncertain whether it may be legitimate to use tests that assume Gaussian errors (e.g. regression, t-test, ANOVA, Gaussian mixed models), or whether one has to either model a more specific error structure or use randomization techniques.Here we use Monte Carlo simulations to explore the pros and cons of fitting Gaussian models to non-normal data in terms of risk of type I error, power and utility for parameter estimation.We find that Gaussian models are remarkably robust to non-normality over a wide range of conditions, meaning that P-values remain fairly reliable except for data with influential outliers judged at strict alpha levels. Gaussian models also perform well in terms of power and they can be useful for parameter estimation but usually not for extrapolation. Transformation of data before analysis is often advisable and visual inspection for outliers and heteroscedasticity is important for assessment. In strong contrast, some non-Gaussian models and randomization techniques bear a range of risks that are often insufficiently known. High rates of false-positive conclusions can arise for instance when overdispersion in count data is not controlled appropriately or when randomization procedures ignore existing non-independencies in the data.Overall, we argue that violating the normality assumption bears risks that are limited and manageable, while several more sophisticated approaches are relatively error prone and difficult to check during peer review. Hence, as long as scientists and reviewers are not fully aware of the risks, science might benefit from preferentially trusting Gaussian mixed models in which random effects account for non-independencies in the data in a transparent way.Tweetable abstractGaussian models are remarkably robust to even dramatic violations of the normality assumption.
A Modeling Framework for Exploring Sampling and Observation Process Biases in Genome and Phenome-wide Association Studies using Electronic Health Records
Authors: Beesley Lauren J. , Fritsche Lars G. , Mukherjee Bhramar 
Published: December 2018

AbstractLarge-scale agnostic association analyses based on existing observational health care databases such as electronic health records have been a topic of increasing interest in the scientific community. However, particular challenges of non-probability sampling and phenotype misclassification associated with the use of these data sources are often ignored in standard analyses. In general, the extent of the bias that may be introduced by ignoring these factors is unknown. In this paper, we develop a statistical framework for characterizing the degree of bias expected in association studies based on electronic health records when disease status misclassification and the sampling mechanism are ignored. Through a sensitivity analysis type approach, this framework can be used to obtain plausible values for parameters of interest given results obtained from standard naive analysis methods under varying degree of misclassification and sampling biases. We develop an online tool for performing this sensitivity analysis in some special cases that occur frequently. Simulations demonstrate promising properties of the proposed way of characterizing biases. We apply our approach to study bias in genetic association studies using data from the Michigan Genomics Initiative, a longitudinal biorepository effort within Michigan Medicine.
Plant breeders should be determining economic weights for a selection index instead of using independent culling for choosing parents in breeding programs with genomic selection
Authors: Batista Lorena G. , Gaynor R. Chris , Margarido Gabriel R. A. , Byrne Tim , Amer Peter , Gorjanc Gregor , Hickey John M. 
Published: December 2018

AbstractIn the context of genomic selection, we evaluated and compared recurrent selection breeding programs using either index selection or independent culling for selection of parents. We simulated a clonally propagated crop breeding program for 20 cycles of selection using either independent culling or an economic selection index with two unfavourably correlated traits under selection. Cycle time from crossing to selection of parents was kept the same for both strategies. Our results demonstrate that accurate knowledge of the economic importance of traits is essential even when performing independent culling. This is because independent culling achieved its optimum genetic gain when the culling threshold for each trait varied accordingly to the economic importance of the traits. When gains from independent culling were maximised, the efficiency of converting genetic diversity into genetic gain of both selection methods were equivalent. When the same proportion selected of 10% for each trait was used instead of optimal culling levels, index selection was 10%, 128% and 310% more efficient than independent culling when T2 had a relative economic importance of 1.0, 2.5 and 5.0, respectively. Given the complexity of estimating optimal culling levels and the fact that the gains achieved with independent culling are, at most, equivalent to index selection, the use of an economic selection index is recommended for multi-trait genomic selection.
An advanced strategy for comprehensive profiling of ADP-ribosylation sites using mass spectrometry-based proteomics
Authors: Hendriks Ivo A. , Larsen Sara C. , Nielsen Michael L. 
Published: December 2018

ABSTRACTADP-ribosylation is a widespread post-translational modification (PTM) with crucial functions in many cellular processes. Here, we describe an in-depth ADP-ribosylome using our Af1521-based proteomics methodology for comprehensive profiling of ADP-ribosylation sites, by systematically assessing complementary proteolytic digestions and precursor fragmentation through application of electron-transfer higher-energy collisional dissociation (EThcD) and electron transfer dissociation (ETD), respectively. While ETD spectra yielded higher identification scores, EThcD generally proved superior to ETD in identification and localization of ADP-ribosylation sites regardless of protease employed. Notwithstanding, the propensities of complementary proteases and fragmentation methods expanded the detectable repertoire of ADP-ribosylation to an unprecedented depth. This system-wide profiling of the ADP-ribosylome in HeLa cells subjected to DNA damage uncovered >11,000 unique ADP-ribosylated peptides mapping to >7,000 ADP-ribosylation sites, in total modifying over one-third of the human nuclear proteome and highlighting the vast scope of this PTM. High-resolution MS/MS spectra enabled identification of dozens of proteins concomitantly modified by ADP-ribosylation and phosphorylation, revealing a considerable degree of crosstalk on histones. ADP-ribosylation was confidently localized to various amino acid residue types, including less abundantly modified residues, with hundreds of ADP-ribosylation sites pinpointed on histidine, arginine, and tyrosine residues. Functional enrichment analysis suggested modification of these specific residue types is directed in a spatial manner, with tyrosine ADP-ribosylation linked to the ribosome, arginine ADP-ribosylation linked to the endoplasmic reticulum, and histidine ADP-ribosylation linked to the mitochondrion.
In situestimation of genetic variation of functional and ecological traits inQuercus petraeaandQ.robur
Authors: Alexandre Hermine , Truffaut Laura , Ducousso Alexis , Louvet Jean-Marc , Nepveu Gérard , Torres-Ruiz José M. , Lagane Frédéric , Firmat Cyril , Musch Brigitte , Delzon Sylvain , Kremer Antoine 
Published: December 2018

AbstractBackgroundPredicting the evolutionary potential of natural tree populations requires the estimation of heritability and genetic correlations among traits on which selection acts, as differences in evolutionary success between species may rely on differences for these genetic parameters.In situestimates are expected to be more accurate than measures done under controlled conditions which do not reflect the natural environmental variance.AimsThe aim of the current study was to estimate three genetic parameters (i.e. heritability, evolvability and genetic correlations) in a natural mixed oak stand composed ofQuercus petraeaandQuercus roburabout 100 years old, for 58 traits of ecological and functional relevance (growth, reproduction, phenology, physiology, resilience, structure, morphology and defence).MethodsFirst we estimated genetic parameters directlyin situusing realized genomic relatedness of adult trees and parentage relationships over two generations to estimate the traits additive variance. Secondly, we benefited from existingex situexperiments (progeny tests and conservation collection) installed with the same populations, thus allowing comparisons ofin situheritability estimates with more traditional methods.ResultsHeritability and evolvability estimates obtained with different methods varied substantially and showed large confidence intervals, however we found thatin situwere less precise thanex situesti-mates, and assessments over two generations (with deeper relatedness) improved estimates of heritability while large sampling sizes are needed for accurate estimations. At the biological level, heritability values varied moderately across different ecological and functional categories of traits, and genetic correlations among traits were conserved over the two species.ConclusionWe identified limits for using realized genomic relatedness in natural stands to estimate the genetic variance, given the overall low variance of genetic relatedness and the rather low sampling sizes of currently used long term genetic plots in forestry. These limits can be overcome if larger sample sizes are considered, or if the approach is extended over the next generation.
Blurred molecular epidemiological lines between the two dominant methicillin-resistant Staphylococcus aureus clones
Authors: Dupper Amy C. , Sullivan Mitchell J. , Chacko Kieran I. , Mishkin Aaron , Ciferri Brianne , Kumaresh Ajay , Caban Ana Berbel , Oussenko Irina , Beckford Colleen , Zeitouni Nathalie E. , Sebra Robert , Hamula Camille , Smith Melissa , Kasarskis Andrew , Patel Gopi , McBride Russell B. , van Bakel Harm , Altman Deena R. 
Published: December 2018

AbstractBackgroundMethicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening infections in both community and hospital settings and is a leading cause of healthcare-associated infections (HAIs). We sought to describe the molecular epidemiological landscape of patients with MRSA bloodstream infections (BSIs) at an urban medical center by evaluating the clinical characteristics associated with the two dominant endemic clones.MethodsComprehensive clinical data extraction from the electronic health records of 227 hospitalized patients ≥18 years old with MRSA BSI over a 33-month period in New York City were collected. The descriptive epidemiology and mortality associated with the two dominant clones was compared using logistic regression.ResultsMolecular analysis revealed that 91% of all single-patient MRSA BSIs were due to two equally represented genotypes, clonal complex (CC) 5 (N=117) and CC8 (N=110). MRSA BSIs were associated with a 90-day mortality of 27%. CC8 caused disease more frequently in younger age groups (56 ± 17 vs 67 ± 17 years old; p<0.001) and in non-White race (OR=3.45 95% CI [1.51-7.87]; p=0.003), with few other major distinguishing features. Morbidity and mortality also did not differ significantly between the two clones. CC8 caused BSIs more frequently in the setting of peripheral intravenous catheters (OR=5.96; 95% CI [1.51-23.50]; p=0.01).ConclusionThe clinical features distinguishing dominant MRSA clones continue to converge. The association of CC8 with peripheral intravenous catheter infections underscores the importance of classical community clones causing hospital-onset infections. Ongoing monitoring and analysis of the dynamic epidemiology of this endemic pathogen is crucial to inform management to prevent disease.