bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional genomics and gene-environment interaction highlight the complexity of congenital heart disease caused by Notch pathway variants
Authors: Chapman Gavin , Moreau Julie L M , I P Eddie , Szot Justin O , Iyer Kavitha R , Shi Hongjun , Yam Michelle X , O’Reilly Victoria C , Enriquez Annabelle , Greasby Joelene A , Alankarage Dimuthu , Martin Ella M M A , Hanna Bernadette C , Edwards Matthew , Monger Steven , Blue Gillian M , Winlaw David S , Ritchie Helen E , Grieve Stuart M , Giannoulatou Eleni , Sparrow Duncan B , Dunwoodie Sally L 
Published: November 2019

AbstractCongenital heart disease (CHD) is the most common birth defect and brings with it significant mortality and morbidity. The application of exome and genome sequencing has greatly improved the rate of genetic diagnosis for CHD but the cause in the majority of cases remains uncertain. It is clear that genetics, as well as environmental influences, play roles in the aetiology of CHD. Here we address both these aspects of causation with respect to the Notch signalling pathway. In our CHD cohort, variants in core Notch pathway genes account for 20% of those that cause disease, a rate that did not increase with the inclusion of genes of the broader Notch pathway and its regulators. This is reinforced by case-control burden analysis where variants in Notch pathway genes are enriched in CHD patients. This enrichment is due to variation in NOTCH1. Functional analysis of some novel missense NOTCH1 and DLL4 variants in cultured cells demonstrate reduced signalling activity, allowing variant reclassification. Although loss-of-function variants in DLL4 are known to cause Adams-Oliver syndrome, this is the first report of a hypomorphic DLL4 allele as a cause of isolated CHD. Finally, we demonstrate a gene-environment interaction in mouse embryos between Notch1 heterozygosity and low oxygen- or anti-arrhythmic drug-induced gestational hypoxia, resulting in an increased incidence of heart defects. This implies that exposure to environmental insults such as hypoxia could explain variable expressivity and penetrance of observed CHD in families carrying Notch pathway variants.
Minor Hematochezia Decreases Use of Venous Thromboembolism Prophylaxis in Patients with Inflammatory Bowel Disease
Authors: Faye Adam S , Hung Kenneth W , Cheng Kimberly , Blackett John W , Mckenney Anna Sophia , Pont Adam R , Li Jianhua , Lawlor Garrett , Lebwohl Benjamin , Freedberg Daniel E 
Published: November 2019

Abstract

Background
Despite increased risk of venous thromboembolism (VTE) among hospitalized patients with inflammatory bowel disease (IBD), pharmacologic prophylaxis rates remain low. We sought to understand the reasons for this by assessing factors associated with VTE prophylaxis in patients with IBD and the safety of its use.

Methods
This was a retrospective cohort study conducted among patients hospitalized between January 2013 and August 2018. The primary outcome was VTE prophylaxis, and exposures of interest included acute and chronic bleeding. Medical records were parsed electronically for covariables, and logistic regression was used to assess factors associated with VTE prophylaxis.

Results
There were 22,499 patients studied, including 474 (2%) with IBD. Patients with IBD were less likely to be placed on VTE prophylaxis (79% with IBD, 87% without IBD), particularly if hematochezia was present (57% with hematochezia, 86% without hematochezia). Among patients with IBD, admission to a medical service and hematochezia (adjusted odds ratio 0.27; 95% CI, 0.16–0.46) were among the strongest independent predictors of decreased VTE prophylaxis use. Neither hematochezia nor VTE prophylaxis was associated with increased blood transfusion rates or with a clinically significant decline in hemoglobin level during hospitalization.

Conclusion
Hospitalized patients are less likely to be placed on VTE prophylaxis if they have IBD, and hematochezia may drive this. Hematochezia appeared to be minor and was unaffected by VTE prophylaxis. Education related to the safety of VTE prophylaxis in the setting of minor hematochezia may be a high-yield way to increase VTE prophylaxis rates in patients with IBD.
Distortions in firm selection during recessions: a comparison across European countries
Authors: Landini Fabio 
Published: November 2019

Abstract
Recent evidence documents the weakness of market selection based on productivity differentials and the absence of cleansing during recessions. This article argues that a possible explanation lies in the role of competitive rents, i.e. market advantages due to idiosyncrasies of the firm’s demand. Competitive rents allow firms to sustain profit independently of their internal efficiency, creating a selection advantage. During an economic recession, this advantage increases because competitive rents operate as a resilience factor. The process of firm selection can thus be distorted with relatively inefficient firms that manage to survive. These predictions are tested on a sample of French, Italian, and Spanish manufacturing firms, looking at the selection that took place during the Great Recession. Ceteris paribus, firms with competitive rents are less likely to exit than firms without competitive rents. This effect is stronger in countries more severely impacted by the downturn. The implications of these results for policy interventions to sustain aggregate productivity growth are discussed.
Determining key drivers of perceptions of performance of rights-based fisheries in Australia using a Bayesian belief network
Authors: Pascoe Sean , Van Putten Ingrid , Hoshino Eriko , Vieira Simon 
Published: November 2019

Abstract
Rights-based management has been advocated as a means of improving the biological sustainability and economic performance of commercial fisheries. The most common forms of rights-based management implemented are individual transferable catch quotas (ITQs) and individual transferable effort quotas (ITEs). Perceptions of success of these management systems vary, however, with some being considered successful while others have been criticized, especially when broad social outcomes are taken into consideration. In this study, we develop a Bayesian belief network model that considers the underlying governance and social environment in which the fishery operates, along with the characteristics of the fishery. We use data derived from a survey of fishers, managers, and scientists to populate the model from 47 Australian fisheries currently managed through ITQs and ITEs. As well as capturing the characteristics of the fisheries, the survey asked respondents for their perceptions on the overall performance of the management system, as well as its performance against social, economic, environmental, and governance objectives. The results suggest that positive perceptions of management performance are related to the quality of social relationships between fishers, the efficiency in the functioning of quota markets, and the degree to which economic information is used in quota setting.
A Mendelian randomization analysis of circulating lipid traits and breast cancer risk
Authors: Beeghly-Fadiel Alicia , Khankari Nikhil K , Delahanty Ryan J , Shu Xiao-Ou , Lu Yingchang , Schmidt Marjanka K , Bolla Manjeet K , Michailidou Kyriaki , Wang Qin , Dennis Joe , Yannoukakos Drakoulis , Dunning Alison M , Pharoah Paul D P , Chenevix-Trench Georgia , Milne Roger L , Hunter David J , Per Hall , Kraft Peter , Simard Jacques , Easton Douglas F , Zheng Wei 
Published: November 2019

Abstract

Background
Conventional epidemiologic studies have evaluated associations between circulating lipid levels and breast cancer risk, but results have been inconsistent. As Mendelian randomization analyses may provide evidence for causal inference, we sought to evaluate potentially unbiased associations between breast cancer risk and four genetically predicted lipid traits.

Methods
Previous genome-wide association studies (GWAS) have identified 164 discrete variants associated with high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides and total cholesterol. We used 162 of these unique variants to construct weighted genetic scores (wGSs) for a total of 101 424 breast cancer cases and 80 253 controls of European ancestry from the Breast Cancer Association Consortium (BCAC). Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between per standard deviation increase in genetically predicted lipid traits and breast cancer risk. Additional Mendelian randomization analysis approaches and sensitivity analyses were conducted to assess pleiotropy and instrument validity.

Results
Corresponding to approximately 15 mg/dL, one standard deviation increase in genetically predicted HDL-C was associated with a 12% increased breast cancer risk (OR: 1.12, 95% CI: 1.08–1.16). Findings were consistent after adjustment for breast cancer risk factors and were robust in several sensitivity analyses. Associations with genetically predicted triglycerides and total cholesterol were inconsistent, and no association for genetically predicted LDL-C was observed.

Conclusions
This study provides strong evidence that circulating HDL-C may be associated with an increased risk of breast cancer, whereas LDL-C may not be related to breast cancer risk.
Whole-Genome Analysis of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Sequence Type 398 Strains Isolated From Patients With Bacteremia in China
Authors: Chen Hongbin , Yin Yuyao , Li Xiaohua , Li Shuguang , Gao Hua , Wang Xiaojuan , Zhang Yawei , Liu Yudong , Wang Hui 
Published: November 2019

Abstract
Sequence type (ST) 398 is the most prevalent clone of livestock-associated methicillin-resistant Staphylococcus aureus (MRSA). To evaluate the molecular characteristics and phylogeny of Chinese ST398 isolates, 4 MRSA ST398 strains and 4 methicillin-susceptible S. aureus (MSSA) ST398 strains were collected from patients with bacteremia at 6 teaching hospitals in China between 1999 and 2016. Moreover, 689 ST398 genome sequences were downloaded from the GenBank database for comparison. The 4 MRSA ST398 strains were resistant to β-lactam antibiotics, and 2 strains were also resistant to erythromycin. Among the 4 MSSA ST398 strains, 2 strains displayed multidrug resistance (MDR) and were resistant to penicillin, erythromycin, tetracycline, and gentamicin. The accessory genome of MSSA ST398 was more diverse than that of MRSA ST398. All 4 MRSA ST398 strains carried type V staphylococcal cassette chromosome mec elements; however, MSSA ST398 carried more resistance genes than MRSA ST398. These 4 MRSA ST398 strains carried hemolysin, along with virulence genes associated with immune invasion and protease. Phylogenic analysis showed that the 4 MRSA ST398 strains clustered in 1 clade. The global ST398 phylogeny showed that ST398 was divided into an animal clade and a human clade, and the ST398 strains of this study clustered in the human clade. A small number of human strains were also present in the animal clade and vice versa, suggesting transmission of ST398 between animals and humans. In conclusion, livestock-associated MRSA ST398 has caused severe infections in Chinese hospitals, and it should therefore be paid more attention to and monitored.
Diagnosis and outcome of resected solitary pulmonary nodules after liver transplantation
Authors: Tone Mari , Awano Nobuyasu , Izumo Takehiro , Yoshimura Hanako , Jo Tatsunori , Kuse Naoyuki , Inomata Minoru , Fukumoto Kento , Furuhata Yoshiaki , Hashimoto Takuya , Kumasaka Toshio , Kunitoh Hideo 
Published: November 2019

Abstract

Objective
Solitary pulmonary nodules after liver transplantation are challenging clinical problems. Herein, we report the causes and clinical courses of resected solitary pulmonary nodules in patients who underwent liver transplantation.

Methods
We retrospectively obtained medical records of 68 patients who underwent liver transplantation between March 2009 and June 2016. This study mainly focused on patients with solitary pulmonary nodules observed on computed tomography scans during follow-ups that were conducted until their deaths or February 2019.

Results
Computed tomography scans revealed solitary pulmonary nodules in 7 of the 68 patients. Definitive diagnoses were obtained using video-assisted lung resection in all seven patients. None experienced major postoperative complications. The final pathologic diagnoses were primary lung cancer in three patients, pulmonary metastases from hepatocellular carcinoma in one patient, invasive pulmonary aspergillosis in one patient, post-transplant lymphoproliferative disorder in one patient, and hemorrhagic infarction in one patient. The three patients with lung cancer were subsequently treated with standard curative resection.

Conclusions
Solitary pulmonary nodules present in several serious but potentially curable diseases, such as early-stage lung cancer. Patients who present with solitary pulmonary nodules after liver transplantation should be evaluated by standard diagnostic procedures, including surgical biopsy if necessary.
Comparative Vector Efficiency of Two Prevalent Mosquito Species for Dog Heartworm in North Carolina
Authors: Spence Beaulieu Meredith R , Reiskind Michael H 
Published: November 2019

AbstractThe dog heartworm, Dirofilaria immitis (Leidy) (Spirurida: Onchocercidae), is a devastating parasite of domestic and wild canines vectored by a multitude of mosquito species. Although many species are implicated as vectors, not all contribute equally to disease transmission, with demonstrated variation in vector efficiency between and within species. We investigated the vector efficiency of mosquitoes derived from wild-caught North Carolina populations of two known heartworm vectors: a native species, Aedes triseriatus (Say) (Diptera: Culicidae), and an invasive species, Aedes albopictus (Skuse). We compared the parasite developmental times within the mosquito, mosquito longevity and fecundity, and the vector efficiency index between the two species. We found that the tested composite North Carolina population of Ae. triseriatus was an efficient vector of D. immitis under laboratory conditions, whereas the local composite population of Ae. albopictus was a competent but relatively poor vector. Compared with Ae. triseriatus, Ae. albopictus showed a longer time for parasite development, lower infection rates, and lower vector efficiency. Additionally, Ae. albopictus was the sole species to exhibit significant parasite-induced mortality. These results are in contrast to prior studies of populations of Ae. albopictus from locations outside of North Carolina, which have implicated the species as a highly competent heartworm vector. The variation seen for different strains of the same species emphasizes the heritable nature of D. immitis vector competence and highlights the need for local infection studies for accurate transmission risk assessment in a particular locale.
The Pseudo Maximum Likelihood Estimator for Quantiles of Survey Variables
Authors: Wang Jing 
Published: November 2019

Abstract
The pseudo maximum likelihood approach has been employed in multilevel models for analysis of complex survey data. This approach may be inappropriate for many survey variables that are nonsymmetrically distributed with skewness and multimodality characteristics. This article intends to fill this gap in the literature by developing a pseudolikelihood estimator for quantiles of survey variables in the quantile regression framework. This approach is illustrated using a Monte Carlo simulation study and the body mass index data from the 1998–1999 Early Childhood Longitudinal Study. Results show that the proposed estimator is consistent and approximately unbiased for both informative and noninformative sampling designs.
γ-Tubulin interacts with E2FA, E2FB and E2FC transcription factors, regulates proliferation and endocycle in Arabidopsis
Authors: Kállai B M , Kourová H , Chumová J , Papdi C , Trögelová L , Kofroňová O , Hozák P , Filimonenko V , Mészáros T , Magyar Z , Bögre L , Binarová P 
Published: November 2019

Abstract
γ-Tubulin is associated with microtubule nucleation, but evidence is accumulating in eukaryotes that it functions also in nuclear processes and in cell division control that are independent of its canonical role. We found that in Arabidopsis thaliana γ-tubulin interacts specifically with E2FA, E2FB, and E2FC transcription factors both in vitro and in vivo. The interaction of γ-tubulin with the E2Fs is not reduced in the presence of the dimerization partners (DPs) and, in agreement, we found that γ-tubulin interaction with E2Fs does not require the dimerization domain. γ-Tubulin associates with the promoters of E2F-regulated cell cycle genes in an E2F dependent manner, likely in complex with the E2F/DP heterodimer. The upregulation of E2F targets; PCNA, ORC2, CDKB1;1 and CCS52A under γtubulin silencing suggests a repressive function for γ-tubulin at G1/S, G2/M and endocycle, which is consistent with an excess of cell division in some cells and enhanced endoreduplication in others in the shoot and young leaves of γ-tubulin RNAi plants. Altogether, our data show ternary interaction of γ-tubulin with E2F/DP heterodimer and suggest a repressive role for γ-tubulin with E2Fs in controlling mitotic activity and endoreduplication during plant development.
Optimally managing hyperkalemia in patients with cardiorenal syndrome
Authors: Wang Angela Yee-Moon 
Published: November 2019

Abstract
Renin–angiotensin–aldosterone system inhibitors (RAASi) are now a standard treatment in most patients with cardiovascular disease, especially in those with heart failure (HF). The European Society of Cardiology and the American College of Cardiology/American Heart Association gave a Class IA recommendation for the use of RAASi in the treatment of Classes II–IV symptomatic HF with reduced ejection fraction (HFREF), based on their strong clinical benefits of lowering all-cause mortality and HF hospitalizations in these subjects. However, RAASi therapy or adding mineralocorticoid receptor antagonists in subjects receiving background angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be associated with an increased risk of hyperkalemia (HK), especially in those with reduced kidney function. As a result, a significant proportion of these subjects either have RAASi dose reduced or more often discontinued when they develop HK. Discontinuation of RAASi in patients hospitalized with HFREF was associated with higher postdischarge mortality and rehospitalization rates, while optimal dosing of RAASi significantly reduced median hospital stays, outpatient visits and related costs. Thus, effective treatment is required to lower potassium level and maintain normokalemia in subjects with HF and reduced kidney disease who develop or are at risk of HK, thus enabling them to continue their RAASi therapy and maximize benefits from RAASi. In this review, we provide an up-to-date review of the prevalence and significance of HK in patients with cardiorenal syndrome, as well as their optimal management of HK with recent novel therapies.
Very Low Nicotine Content Cigarettes Disrupt the Feedback Loop of Affective States and Smoking Behavior
Authors: Robinson Jason D , Kypriotakis George , Al’absi Mustafa , Denlinger-Apte Rachel L , Drobes David J , Leischow Scott J , McClernon F Joseph , Pacek Lauren R , Severson Herbert H , Smith Tracy T , Donny Eric C , Luo Xianghua , Jensen Joni A , Strayer Lori G , Cinciripini Paul M , Hatsukami Dorothy K 
Published: November 2019

Abstract

Introduction
Smoking to reduce negative affect has been identified as a key motivational feature of tobacco use. Our recent work suggests that smoking very low nicotine content (VLNC) cigarettes reduces the relationship between negative affect and smoking behavior over a 6-week period. Here, we sought to extend our findings by evaluating whether a gradual or immediate approach to switching to VLNC cigarettes led to a differential reduction in the relationship between affect and smoking behavior over a longer (20-week) period.

Aims and Methods
Participants (n = 1250) were adult smokers from 10 US sites randomized to one of three groups: gradual nicotine reduction (15.5, 11.7, 5.2, 2.4, and 0.4 mg of nicotine per gram of tobacco [mg/g]), immediate nicotine reduction (0.4 mg/g), or standard nicotine content cigarettes (15.5 mg/g; control), for 20 weeks. We examined whether the relationship between affect—both negative and positive—and cigarettes per day differed as a function of reduction group.

Results
We found that both negative and positive affect were associated with cigarette consumption in the control group, but not in the gradual or immediate reduction groups across the 20 weeks of exposure.

Conclusions
Our results extend previous findings that switching to VLNC cigarettes disrupts the relationship between affect and cigarette consumption by showing that either gradually or immediately reducing cigarette nicotine content achieves this disruption. These findings provide further evidence that switching to VLNC cigarettes reduces nicotine-related reinforcement of cigarette smoking.

Implications
These findings support the notion that switching to very low nicotine content cigarettes reduces the association between affect and smoking behavior, and that either a gradual or immediate nicotine reduction approach achieves this reduction. This provides further evidence that switching to very low nicotine content cigarettes weakens reinforcement mechanisms associated with nicotine dependence.
Predictors of Acute Liver Failure in Patients With Acute Hepatitis A: An Analysis of the 2016–2018 San Diego County Hepatitis A Outbreak
Authors: Jiang Aiyang A , Greenwald Holly S , Sheikh Lamiya , Wooten Darcy A , Malhotra Atul , Schooley Robert T , Sweeney Daniel A 
Published: November 2019

Abstract

Background
Between 2016 and 2018, San Diego County experienced a hepatitis A outbreak with a historically high mortality rate (3.4%) that highlighted the need for early recognition of those at risk of developing acute liver failure (ALF).

Methods
A retrospective case series of adult hospitalized patients with acute hepatitis A.

Results
One hundred six patients with hepatitis A were studied, of whom 11 (10.4%) developed ALF, of whom 7 (6.6%) died. A history of alcohol abuse, hyperbilirubinemia, hypoalbuminemia, hyponatremia, and anemia were associated with increased odds of developing ALF. Initial Maddrey’s and Model of End-Stage Liver Disease Sodium (MELD-Na) scores were also associated with the development of ALF. Multivariable analysis showed that a higher initial MELD-Na score (odds ratio [OR], 1.205; 95% confidence interval [CI], 1.018–1.427) and a lower initial serum albumin concentration (OR, 9.35; 95% CI, 1.15–76.9) were associated with increased odds of developing ALF. Combining serum albumin and MELD-Na (SAM; C-statistic, 0.8878; 95% CI, 0.756–0.988) yielded a model that was not better than either serum albumin (C-statistic, 0.852; 95% CI, 0.675–0.976) or MELD-Na (C-statistic, 0.891; 95% CI, 0.784–0.968; P = .841). Finally, positive blood cultures were more common among patients with ALF compared with those without ALF (63.6% vs 4.3%; P < .00001).

Conclusions
Hypoalbuminemia was associated with an increased risk of ALF in patients with acute hepatitis A. Positive blood cultures and septic shock as a cause of death were common among patients with ALF. Providers caring for patients with acute hepatitis A should monitor for early signs of sepsis and consider empiric antibiotics, especially in patients presenting with hypoalbuminemia.