bluuebunny/crossref_metadata_2025 huggingface dataset:
Percentage low-density lipoprotein-cholesterol response to a given statin dose is not fixed across the pre-treatment range: Real world evidence from clinical practice: Data from the ESC-EORP EUROASPIRE V Study
Authors: Bacquer Dirk De , Smedt Delphine De , Reiner Željko , Tokgözoğlu Lale , Clays Els , Kotseva Kornelia , Rydén Lars , Wood David , Backer Guy De
Published: September 2019

Aims

Recent European guidelines recommend in patients with atherosclerotic cardiovascular disease to achieve a reduction of low-density lipoprotein-cholesterol of at least 50% if the baseline low-density lipoprotein-cholesterol level is between 1.8 and 3.5 mmol/L. Systematic reviews have associated a given statin/dose combination with a fixed percentage low-density lipoprotein-cholesterol response. Algorithms for detecting cases and estimating the prevalence of familial hypercholesterolaemia often rely on such fixed percentage reductions.

Methods and results

We used data from 915 coronary patients participating in the EUROASPIRE V study in whom atorvastatin or rosuvastatin therapy was initiated at hospital discharge and who were still using these drugs at the same dose at a follow-up visit 6 or more months later. Pre and on-treatment low-density lipoprotein-cholesterol levels were compared across the full low-density lipoprotein-cholesterol range. The prevalence of FH was estimated using the Dutch Lipid Clinic Network criteria, once using observed pre-treatment low-density lipoprotein-cholesterol and once using imputed pre-treatment low-density lipoprotein-cholesterol by following the common strategy of applying fixed correction factors to on-treatment low-density lipoprotein-cholesterol. Inter-individual variation in the low-density lipoprotein-cholesterol response to a fixed statin and dose was considerable, with a strong inverse relation of percentage reductions to pre-treatment low-density lipoprotein-cholesterol. The percentage low-density lipoprotein-cholesterol response was markedly lower at the left end of the pre-treatment low-density lipoprotein-cholesterol range especially for levels less than 3 mmol/L. The estimated prevalence of familial hypercholesterolaemia was 2% if using observed pre-treatment low-density lipoprotein-cholesterol and 10% when using imputed low-density lipoprotein-cholesterol.

Conclusion

The inter-individual variation in the percentage low-density lipoprotein-cholesterol response to a given dose of a statin is largely dependent on the pre-treatment level: the lower the pre-treatment low-density lipoprotein-cholesterol level the smaller the percentage low-density lipoprotein-cholesterol reduction. The use of uniform correction factors to estimate pre-treatment low-density lipoprotein-cholesterol is not justified.
The therapeutic activity of curcumin through its anti-cancer potential on oral squamous cell carcinoma: A study on Sprague Dawley rat
Authors: Maulina Tantry , Hadikrishna Indra , Hardianto Andri , Sjamsudin Endang , Pontjo Bambang , Yusuf Harmas Yazid
Published: September 2019

Objectives:

Being the most common type of oral malignancies, oral squamous cell carcinoma is initiated by epithelial dysplasia, which can be marked by the expression of nuclear factor kappa B and cyclooxygenase 2. Curcumin has been known for its anti-cancer potential. The objective of this study was to evaluate the anti-cancer potential of curcumin on oral squamous cell carcinoma based on the expression of the nuclear factor kappa B and cyclooxygenase 2 during epithelial dysplasia stage.

Methods:

This experimental study was performed on 35 Sprague Dawley rats at the Veterinary Medicine Faculty, Bogor Agricultural Institute, Indonesia. At the beginning of the experiments, all rats were induced by 100 µg 0.5% 7,12-dimethylbenz(a)anthracene every 2 days for the duration of 28 days. Once epithelial dysplasia stage was reached, all rats were then randomly divided into control group (that did not receive curcumin) or the experimental group (the group that received curcumin for the next 4 weeks). After 4 weeks, the histopathological examination of haematoxylin and eosin and immunohistochemistry examination were conducted. Data were gathered and analyzed by using the Wilcoxon–Mann–Whitney test.

Results:

The results of the current study revealed that the experimental group showed significantly less nuclear factor kappa B (p < 0.01) and cyclooxygenase 2 (p = 0.03) expressions compared to the control group.

Conclusion:

The results of the study suggested that curcumin was effective in suppressing nuclear factor kappa B and cyclooxygenase 2 expression in experimentally induced oral squamous cell carcinoma. Future studies investigating curcumin anti-cancer potential in a further stage of oral squamous cell carcinoma, as well as the involvement of other components that might improve curcumin anti-cancer potential, are of importance.
Occurrence of feline immunodeficiency virus and feline leukaemia virus in Maputo city and province, Mozambique: a pilot study
Authors: Tchamo Cesaltina CLM , De Rugeriis Mónica , Noormahomed Emília V
Published: September 2019

Objectives

Feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) are immunosuppressive viruses in cats that increase their susceptibility to zoonotic pathogens. This study aimed to determine the occurrence of one or both viruses, the risk factors associated with infection, and to develop further recommendations.

Methods

This was a cross-sectional study conducted at the Veterinary Faculty of Eduardo Mondlane University, Mozambique, between March and December 2017, in 145 cats. From each of 145 cats, we took 1.5 ml of blood by jugular puncture for detection of antibodies to FIV and FeLV antigens in whole blood using a commercial test kit, DFV Test FeLV/FIV.

Results

We found an overall prevalence of 11.0% and 14.5% for FIV antibodies and FeLV antigens, respectively, with four (2.8%) cats coinfected by both pathogens. Male cats were more likely to be infected with FIV (odds ratio [OR] 1.1, 95% confidence interval [CI] 0.3–4.0) compared with female cats. Clinically ill cats were more likely to have a positive result for FeLV antigen infection (OR 18.8, 95% CI 5.2–68.3). Moreover, cats living in suburban areas have a greater chance of a positive result for FeLV infection (OR 3.7, 95% CI 1.4–9.6) compared with cats living in urban areas.

Conclusions and relevance

FIV and FeLV occur in cats from Maputo and possibly all over the country. Further studies should be conducted in Mozambique and other African countries to define the burden of both pathogens in cats, coinfection with other zoonotic pathogens and the possible role played by the cats on the transmission of zoonotic and opportunistic diseases to humans.
Extracorporeal Cardiopulmonary Resuscitation (ECPR) in Infants and Children: A Single-Center Retrospective Study
Authors: Shakoor Aqsa , Pedroso Felipe E. , Jacobs Shimon E. , Okochi Shunpei , Zenilman Ariela , Cheung Eva W. , Middlesworth William
Published: September 2019

Background:

Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used to rescue patients with cardiac arrest refractory to conventional therapy, necessitating evaluation of factors that may affect outcomes.

Methods:

A single-center retrospective review of pediatric patients (<21 years old) who underwent ECPR from January 2010 to November 2017. Comparisons between nonsurvivors and survivors, to decannulation and discharge, were made. Factors associated with survival and rate of complications were examined.

Results:

Seventy patients were supported with ECPR. Forty-nine (70%) patients survived to decannulation and 38 (54%) patients to discharge. There was no statistical difference between baseline characteristics of survivors and nonsurvivors, including age at cannulation, weight (kg), time to cannulation (minutes), and total time on extracorporeal membrane oxygenation (hours). Survivors to discharge had significantly higher pH prior to cannulation compared to nonsurvivors (7.11 ± 0.24 vs 6.97 ± 0.21, P = .01). Of all, 23.2% of patients received renal replacement therapy (RRT), 39.4% had significant bleeding, 22.5% had thrombotic complications, and 68.8% had neurologic injury on imaging studies. A greater number of nonsurvivors received RRT compared to survivors to discharge (35.5% vs 10.8%, P = .02). There were no differences in bleeding or thrombotic complications or radiographically established neurologic injury.

Conclusions:

Although ECPR effectively increases overall survival, a better characterization of long-term outcomes is needed.
Determinants of Exports: A Gravity Model Analysis of the Bangladeshi Textile and Clothing Industries
Authors: Rahman Redwanur , Shahriar Saleh , Kea Sokvibol
Published: September 2019

The purpose of this study is to find out the determinants and issues influencing Bangladeshi textile and clothing (T&C) exports. A unique data set has been generated and used to estimate the panel gravity model of Bangladeshi T&C export flows to a total of its 40 trade partners over a period of 27 years, spanning from 1990 to 2017. The results show that the gross domestic product (GDP), real exchange rate and per capita GDP of the importers have appeared to be major determinants of Bangladesh’s textile exports trade. Also, Bangladesh and World Trade Organization membership have a strong positive significant impact on T&C exports. The geographical distance has no strong significant effect on textile trading. It is found that European Union and North American Free Trade Agreement countries are the two important export destinations for the garments of Bangladesh. This study is a novel and significant contribution for a couple of reasons: First, Bangladesh’s major trading partners are covered in this study sample. Second, the article’s focus on the gravity panel data analysis fills up a major research gap on the determinants of exports of the Bangladeshi garments. This study will thus pave the new avenues for further research in future.
CAMELS-Based Supervision and Risk Management: What Works and What Does Not
Authors: Risal Hari Gopal , Panta Sabin Bikram
Published: September 2019

This paper investigates the effectiveness of CAMELS (Capital Adequacy, Assets Quality, Management Efficiency, Earning Efficiency, Liquidity and Sensitivity to Market Risk) based supervision in risk management of A class commercial banks. The riskiness is measured by Downside Deviation (i. e., volatility of returns below minimum average return) and Standard Deviation of ROA and ROE. Using the Generalized Method of Moments (GMM) in secondary balanced panel data during major financial development (i. e., 2004 to 2018; BASEL-I-II-III) of all 28 commercial banks of Nepal; causal relationship between supervision and risk management has been investigated. The result shows that the commercial banks in Nepal can reduce their downside deviation as well as standard deviation of ROA and ROE by reducing the Non-Performing Loan (NPL), maintaining appropriate liquidity and by increasing management efficiency. Further, results justifies the relevance of risk based supervision adopted by central bank and interest spread set. However, increased capital base has not helped in reducing riskiness of banks. Overall, the study finds that among the six parameters of supervision (i. e., CAMELS), five parameters (i. e., AMELS in the priority order of AMLSE) are capable enough to reduce the riskiness of commercial banks if maintained strictly as guided by the central bank.
Mixed Messages: I. The Consequences of Communicating Negative Statements Within Emotional Support Messages to Cancer Patients
Authors: Ray Colter D , Floyd Kory , Tietsort Cris J , Veluscek Alaina M , Otmar Christopher D , Hashi Emi C , Fisher Rosalie
Published: September 2019

Background:

Not all emotional support messages consist purely of positive statements. Some emotional support messages received by cancer patients simultaneously communicate statements of caring but also negative statements, such as criticisms of patients’ actions.

Objective:

This study tests if a negative statement occurring within an emotional support message affects cancer patients’ perceptions of the effectiveness of the entire emotional support message as well as the perceived competence of the supporter communicating the emotional support message.

Methods:

Cancer patients watched video recordings of emotional support messages and subsequently provided ratings on message effectiveness and supporter competence. Some emotional support messages included negative statements, whereas other messages did not.

Results:

Messages that included a negative statement were rated lower on message effectiveness than messages without negative statements. Cancer patients rated supporters communicating messages with a negative statement as having significantly less competence than those who did not communicate a negative statement.

Conclusion:

A single negative statement occurring within an emotional support message may result in cancer patients viewing the emotional support as less effective and the supporter as less competent.
Predicting Layoff among Fragile Families
Authors: Ahearn Caitlin E. , Brand Jennie E.
Published: September 2019

The loss of a job is the loss of a major social and economic role and is associated with long-term negative economic and psychological consequences for workers and families. Modeling the causal effects of a social process like layoff with observational data depends crucially on the degree to which the model accounts for the characteristics that predict loss. We report analyses predicting layoff in the Fragile Families data as part of the Fragile Families Challenge. Our model, grounded in empirical social science research on layoff, did not perform substantially worse than the best-performing model using data science techniques. This result is not fully unforeseen, given that layoff functions as a relatively exogenous shock. Future work using the results of the Challenge should attend to whether small improvements in prediction models, like those we observe across models of layoff, nevertheless significantly increase the validity of subsequent models for causal inference.
When 4 ≈ 10,000: The Power of Social Science Knowledge in Predictive Performance
Authors: McKay Stephen
Published: September 2019

Computer science has devised leading methods for predicting variables; can social science compete? The author sets out a social scientific approach to the Fragile Families Challenge. Key insights included new variables constructed according to theory (e.g., a measure of shame relating to hardship), lagged values of the target variables, using predicted values of certain outcomes to inform others, and validated scales rather than individual variables. The models were competitive: a four-variable logistic regression model was placed second for predicting layoffs, narrowly beaten by a model using all the available variables (>10,000) and an ensemble of algorithms. Similarly, a relatively small random forest model (25 variables) was ranked seventh in predicting material hardship. However, a similar approach overfitted the prediction of grit. Machine learning approaches proved superior to linear regression for modeling the continuous outcomes. Overall, social scientists can contribute to predictive performance while benefiting from learning more about data science methods.
Privacy, Ethics, and Data Access: A Case Study of the Fragile Families Challenge
Authors: Lundberg Ian , Narayanan Arvind , Levy Karen , Salganik Matthew J.
Published: September 2019

Stewards of social data face a fundamental tension. On one hand, they want to make their data accessible to as many researchers as possible to facilitate new discoveries. At the same time, they want to restrict access to their data as much as possible to protect the people represented in the data. In this article, we provide a case study addressing this common tension in an uncommon setting: the Fragile Families Challenge, a scientific mass collaboration designed to yield insights that could improve the lives of disadvantaged children in the United States. We describe our process of threat modeling, threat mitigation, and third-party guidance. We also describe the ethical principles that formed the basis of our process. We are open about out process and the trade-offs we made in the hope that others can improve on what we have done.
Using LASSO to Assist Imputation and Predict Child Well-being
Authors: Stanescu Diana , Wang Erik , Yamauchi Soichiro
Published: September 2019

This article documents an approach to predicting children’s well-being using data from the Fragile Families and Child Wellbeing Study, which are representative of births in large U.S. cities. The authors use the least absolute shrinkage and selection operator (LASSO) to preprocess the data. They then apply the Amelia algorithm to impute missing data. Finally, they use LASSO again for prediction with the imputed data. The authors report the performance of this approach for six outcome variables. The approach achieves the best performance for the variable material hardship. The out-of-sample mean squared error of the authors’ prediction is 0.019, the lowest among all submissions in the Fragile Families Challenge. The authors find that among variables with high predictive power, variables from mother surveys dominate. Furthermore, components of material hardship in the past strongly predict current material hardship.
Winning Models for Grade Point Average, Grit, and Layoff in the Fragile Families Challenge
Authors: Rigobon Daniel E. , Jahani Eaman , Suhara Yoshihiko , AlGhoneim Khaled , Alghunaim Abdulaziz , Pentland Alex “Sandy” , Almaatouq Abdullah
Published: September 2019

In this article, the authors discuss and analyze their approach to the Fragile Families Challenge. The data consisted of more than 12,000 features (covariates) about the children and their parents, schools, and overall environments from birth to age 9. The authors’ modular and collaborative approach parallelized prediction tasks and relied primarily on existing data science techniques, including (1) data preprocessing: elimination of low variance features, imputation of missing data, and construction of composite features; (2) feature selection through univariate mutual information and extraction of nonzero least absolute shrinkage and selection operator coefficients; (3) three machine learning models: random forest, elastic net, and gradient-boosted trees; and finally (4) prediction aggregation according to performance. The top-performing submissions produced winning out-of-sample predictions for three outcomes: grade point average, grit, and layoff. However, predictions were at most 20 percent better than a baseline that predicted the mean value of the training data for each outcome.
Imputing Data for the Fragile Families Challenge: Identifying Similar Survey Questions with Semiautomated Methods
Authors: Goode Brian J. , Datta Debanjan , Ramakrishnan Naren
Published: September 2019

The Fragile Families Challenge charged participants to predict six outcomes for 4,242 children and their families interviewed in the Fragile Families and Child Wellbeing Study. These outcome variables are grade point average, grit, material hardship, eviction, layoff and job training. The data set provided contained longitudinal survey and observational data collected on families and their children from birth to age 9. The authors used these data to create models to make predictions at age 15. The authors describe the imputation and modeling strategies that led them to make predictions ranked fifth and ninth in the material hardship and layoff categories, respectively. However, the results of the study are inconclusive with respect to increased predictive performance. The authors view this work as a first step toward organizing the Fragile Families missing data by exploiting the structure of the survey instruments.
Predicting GPA at Age 15 in the Fragile Families and Child Wellbeing Study
Authors: Raes Louis
Published: September 2019

In this paper, we describe in detail the different approaches we used to predict the GPA of children at the age of 15 in the context of the Fragile Families Challenge. Our best prediction improved about 18 percent in terms of mean squared error over a naive baseline prediction and performed less than 5 percent worse than the best prediction in the Fragile Families Challenge. After discussing the different predictions we made, we also discuss the predictors that tend to be robustly associated with GPA. One remarkable predictor is related to teacher observations at the age of nine. We end with a reflection on our participation in the Fragile Families Challenge and provide some suggestions for follow-up work.
Introduction to the Special Collection on the Fragile Families Challenge
Authors: Salganik Matthew J. , Lundberg Ian , Kindel Alexander T. , McLanahan Sara
Published: September 2019

The Fragile Families Challenge is a scientific mass collaboration designed to measure and understand the predictability of life trajectories. Participants in the Challenge created predictive models of six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. This Special Collection includes 12 articles describing participants’ approaches to predicting these six outcomes as well as 3 articles describing methodological and procedural insights from running the Challenge. This introduction will help readers interpret the individual articles and help researchers interested in running future projects similar to the Fragile Families Challenge.
Making of Comfortable Exile Through Sanskritization: Reflections on Imagination of Identity Notions in India
Authors: Balan Binesh
Published: September 2019

‘Sanskritization’ refers to the assimilation of local culture of non-Hindus into Hinduism and its social structure, including the caste system. ‘Comfortable Exile’ refers to the internal displacement of an identifiable group, as further defined and discussed below. This study examines how Sanskritization has resulted in comfortable exile and determined the perceived identity of native peoples in the larger Indian society. The narrative revolves around the question of whether being ‘Indian’ must mean being ‘Hindu’.
Encountering the burn: Prescribed burns as contact zones
Authors: Sutherland Colin R
Published: September 2019

Encounters with fire and landscapes that burn have the potential to be both disastrous and life-giving events. In Canadian national parks, where a century of fire suppression has ruled human encounters with fire adapted landscapes, fire managers and ecologists are eagerly returning fire to diverse ecosystems in the hopes of building healthier ecosystems and reducing the risk of larger wildfire events. Ongoing changes to park policy have made new relationships with fire possible on these federal lands. Prescribed burns, whereby fire is applied to the landscape by park managers, is one such emerging encounter made possible by these policy changes. By reconceptualizing the burn as a process constituted by encounters, in what Mary Louise Pratt would call a contact zone, we gain insight into how thinking and working with fire requires an attention to how humans and more-than-humans encounter one another and the institutional settings which narrate and often constrain these encounters. In the case of Parks Canada’s fire program, this tool of active management, and an alternative to full-suppression, illustrates how thinking and working with fire consists of a set of encounters which take place at both an institutional and embodied scale.
Examining the relationship between the needs of children and young persons living in residential care and critical incidents using the Singapore CANS assessment tool
Authors: Chng Grace S. , Yip Wan Fen , Pek Lydia , Ting Ming Hwa , Chu Chi Meng
Published: September 2019

Children and young persons (CYPs) in out-of-home care often demonstrate a variety of needs resultant from their early adverse experiences and complex family backgrounds. In Singapore, the Child and Adolescent Needs and Strengths (CANS) assessment tool is used to capture the individual’s needs and strengths for case planning. This study had two aims: first, it sought to test whether CYPs who entered residential care with higher level-of-care (LoC) scores on the CANS tool, indicative of higher needs or more intensive services required, were more likely to experience a critical incident. Second, it aimed to test the various needs separately with the occurrence of critical incidents to delineate the impact of each individual need on critical incident. Using a sample of 488 CYPs aged between 5 years and 17 years who were residing in 13 voluntary children’s homes in Singapore, the study found that 46.3% of the sample had experienced a critical incident. The results showed that CYPs with higher LoC scores were more likely to have a critical incident, although this comparison was only significant between the lowest and highest LoC scores. Child-related issues such as the presence of self-harm and risk of suicide, behavioral problems, emotional problems, sexual behavior, delinquency, and poor caregiver bond at entry to residential care were also observed to be significantly associated with the occurrence of critical incidents. The findings and implications are discussed accordingly.
Detailed characterisation of the tuberculosis epidemic in Western Sydney: a descriptive epidemiological study
Authors: Norton Sophie , Bag Shopna K. , Cho Jin-Gun , Heron Neil , Assareh Hassan , Pavaresh Laila , Corbett Stephen , Marais Ben J.
Published: September 2019

Traditional tuberculosis (TB) epidemiology reports rarely provide a detailed analysis of TB incidence in particular geographic locations and among diverse population groups. Western Sydney Local Health District (WSLHD) has one of the highest TB incidence rates in Australia, and we explored whether more detailed epidemiological analysis could provide a better overview of the local disease dynamics.

Using multiple relevant data sources, we performed a retrospective descriptive study of TB cases diagnosed within the WSLHD from 2006 to 2015 with a specific focus on geographic hotspots and the population structure within these hotspots.

Over the study period nearly 90% of Western Sydney TB cases were born in a high TB incidence country. The TB disease burden was geographically concentrated in particular areas, with variable ethnic profiles in these different hotspots. The most common countries of birth were India (33.0%), the Philippines (11.4%) and China (8.8%). Among the local government areas in Western Sydney, Auburn had the highest average TB incidence (29.4 per 100 000) with exceptionally high population-specific TB incidence rates among people born in Nepal (average 223 per 100 000 population), Afghanistan (average 154 per 100 000 population) and India (average 143 per 100 000 population).

Similar to other highly cosmopolitan cities around the world, the TB burden in Sydney showed strong geographic concentration. Detailed analysis of TB patient and population profiles in Western Sydney should guide better contextualised and culturally appropriate public health strategies.
Assessment of pesticides in surface water samples from Swedish agricultural areas by integrated bioanalysis and chemical analysis
Authors: Lundqvist Johan , von Brömssen Claudia , Rosenmai Anna Kjerstine , Ohlsson Åsa , Le Godec Theo , Jonsson Ove , Kreuger Jenny , Oskarsson Agneta
Published: September 2019

Background

Pesticide residue contamination of surface water in agricultural areas can have adverse effects on the ecosystem. We have performed an integrated chemical and bioanalytical profiling of surface water samples from Swedish agricultural areas, aiming to assess toxic activity due to presence of pesticides. A total of 157 water samples were collected from six geographical sites with extensive agricultural activity. The samples were chemically analyzed for 129 commonly used pesticides and transformation products. Furthermore, the toxicity was investigated using in vitro bioassays in the water samples following liquid–liquid extraction. Endpoints included oxidative stress response (Nrf2 activity), estrogen receptor (ER) activity, and aryl hydrocarbon receptor (AhR) activity. The bioassays were performed with a final enrichment factor of 5 for the water samples. All bioassays were conducted at non-cytotoxic conditions.

Results

A total of 51 pesticides and transformation products were detected in the water samples. Most of the compounds were herbicides, followed by fungicides, insecticides and transformation products. The highest total pesticide concentration in an individual sample was 39 µg/L, and the highest median total concentration at a sample site was 1.1 µg/L. The largest number of pesticides was 31 in a single sample. We found that 3% of the water samples induced oxidative stress response, 23% of the samples activated the estrogen receptor, and 77% of the samples activated the aryl hydrocarbon receptor. Using Spearman correlation coefficients, a statistically significant correlation was observed between AhR and ER activities, and AhR activity was strongly correlated with oxidative stress in samples with a high AhR activity. Statistically significant relationships were observed between bioactivities and individual pesticides, although the relationships are probably not causal, due to the low concentrations of pesticides. Co-occurrence of non-identified chemical pollutants and naturally occurring toxic compounds may be responsible for the induced bioactivities.

Conclusions

This study demonstrated that integrated chemical analysis and bioanalysis can be performed in water samples following liquid/liquid extraction with a final enrichment factor of 5. AhR and ER activities were induced in water samples from agricultural areas. The activities were presumably not caused by the occurrence of pesticides, but induced by other anthropogenic and natural chemicals.
BINDER: computationally inferring a gene regulatory network for Mycobacterium abscessus
Authors: Staunton Patrick M. , Miranda-CasoLuengo Aleksandra A. , Loftus Brendan J. , Gormley Isobel Claire
Published: September 2019

Background

Although many of the genic features inMycobacterium abscessushave been fully validated, a comprehensive understanding of the regulatory elements remains lacking. Moreover, there is little understanding of how the organism regulates its transcriptomic profile, enabling cells to survive in hostile environments. Here, to computationally infer the gene regulatory network forMycobacterium abscessuswe propose a novel statistical computational modelling approach: BayesIan gene regulatory Networks inferreD via gene coExpression and compaRative genomics (BINDER). In tandem with derived experimental coexpression data, the property of genomic conservation is exploited to probabilistically infer a gene regulatory network inMycobacterium abscessus.Inference on regulatory interactions is conducted by combining ‘primary’ and ‘auxiliary’ data strata. The data forming the primary and auxiliary strata are derived from RNA-seq experiments and sequence information in the primary organismMycobacterium abscessusas well as ChIP-seq data extracted from a related proxy organismMycobacterium tuberculosis. The primary and auxiliary data are combined in a hierarchical Bayesian framework, informing the apposite bivariate likelihood function and prior distributions respectively. The inferred relationships provide insight to regulon groupings inMycobacterium abscessus.

Results

We implement BINDER on data relating to a collection of 167,280 regulator-target pairs resulting in the identification of 54 regulator-target pairs, across 5 transcription factors, for which there is strong probability of regulatory interaction.

Conclusions

The inferred regulatory interactions provide insight to, and a valuable resource for further studies of, transcriptional control inMycobacterium abscessus, and in the family ofMycobacteriaceaemore generally. Further, the developed BINDER framework has broad applicability, useable in settings where computational inference of a gene regulatory network requires integration of data sources derived from both the primary organism of interest and from related proxy organisms.
Prevalence of feet and ankle arthritis and their impact on clinical indices in patients with rheumatoid arthritis: a cross-sectional study
Authors: Lee Sung Won , Kim Seong-Yong , Chang Sung Hae
Published: September 2019

Background

We aimed to evaluate the prevalence of foot and/or ankle arthritis (FAA) and its impact on clinical indices in patients with rheumatoid arthritis (RA).

Methods

This cross-sectional study used data from the Korean College of Rheumatology Biologics & Targeted therapy registry to observe clinical outcomes of patients undergoing biologics therapy and conventional therapy. FAA was defined as ≥1 tender or swollen joint in the ankle and/or 1st-5th metatarsophalangeal (MTP) joints. Disease Activity Score 28 (DAS28), Routine Assessment of Patient Index Data 3 (RAPID3), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) were assessed.

Results

Among 2046 patients, 598 had FAA. The ankle joint was the most commonly involved joint in FAA (tender joint, 71.4%; swollen joint, 59.5%), followed by the third and second MTP joints. Patients with FAA showed higher DAS28, RAPID3, SDAI, and CDAI scores. FAA presence was significantly associated with non-remission as per DAS28-ESR (odds ratio, 3.4; 95% confidence interval, 2.0–5.8), DAS28-CRP (3.6, 2.4–5.3), SDAI (6.3, 2.8–14.6), CDAI (7.6, 2.4–24.3), and RAPID3 (5.6, 2.7–11.5) indices on adjusting for age, sex, disease duration, presence of rheumatoid factor, presence of anti-cyclic citrullinated peptide antibody, lung disease, use of methotrexate, and previous use of biological disease-modifying anti-rheumatic drugs. Patients with FAA were less likely to achieve remission of SDAI (n = 6, 1.0%) and CDAI (n = 3, 0.5%) than that of DAS28-ESR (n = 21, 3.5%), DAS28-CRP (n = 38, 6.4%), and RAPID3 (n = 12, 2.0%).

Conclusions

FAA represents a severe disease activity and is an independent risk factor for non-remission in patients with RA.
Predictors of substantial improvement in physical function six months after lumbar surgery: is early post-operative walking important? A prospective cohort study
Authors: Gilmore Sarah J. , Hahne Andrew J. , Davidson Megan , McClelland Jodie A.
Published: September 2019

Background

Resuming walking after lumbar surgery is a common focus of early post-operative rehabilitation, however there is no knowledge about whether increased walking is associated with better functional outcomes. This study aimed to determine whether time spent walking in the week after lumbar surgery, along with co-morbidities, pre-operative pain duration, pre-operative physical activity or function, or surgical variables predict substantial improvement in physical function six months after lumbar surgery.

Methods

A prospective cohort study design was utilized. Participants undergoing lumbar surgery (discectomy, decompression, fusion) were recruited between April and November 2016. Predictor variables were collected pre-operatively (age, sex, smoking status, obesity, diabetes, depression, anxiety, pre-operative pain duration, neurological deficit, physical activity levels, mobility restriction, function) and early post-operatively (post-operative walking time, surgical procedure, single/multi-level surgery). Outcome variables (physical function, back pain and leg pain severity) were measured pre-operatively and six-months post-operatively. Logistic regression analysis was used to establish prediction of substantial improvement in outcome at six months.

Results

Participants (N = 233; 50% female; age 61 (SD = 14) years) who walked more in the first post-operative week were more likely to have substantially improved function on the Oswestry Disability Questionnaire at six months (OR 1.18, 95%CI 1.02–1.37), as were participants with < 12 months pre-operative pain (OR 2.71, 95%CI 1.28–5.74), and those with lower pre-operative function (OR 4.02, 95%CI 2.33–6.93). Age < 65 years (OR 2.36, 95%CI 1.14–4.85), and < 12 months pre-operative pain (OR 3.52 95%CI 1.69–7.33) predicted substantial improvement on the SF-36 Physical Component Summary. There were no significant predictors for substantial improvement in either leg or back pain.

Conclusions

Walking time in the week after lumbar surgery is one of several predictors of substantial improvement in function at six months. Further research is required to determine whether intervention designed to increase walking early after lumbar surgery results in improved longer-term recovery of function.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR), registration number 12616000747426. Retrospectively registered on the 7th of June 2016.
Estrogen receptors genotypes and canine mammary neoplasia
Authors: Canadas-Sousa Ana , Santos Marta , Leal Bárbara , Medeiros Rui , Dias-Pereira Patrícia
Published: September 2019

Background

Estrogens are essential for the development and proper function of several hormone-dependent organs. There are, however, several lines of evidence associating estrogens with mammary carcinogenesis. A marked individual genetic variability concerning estrogens biosynthesis, metabolism and mechanism of action was recognized and associated with human breast cancer susceptibility, clinical features and progression. Although some genetic variations in canineESR1 genewere reported, their influence in clinicopathological features and progression of canine mammary tumors has not been fully evaluated. This study aims to assess the influence of SNPs inESR1 gene(rs397512133, rs397510462, rs851327560, rs397510612, rs852887655, rs852684753 and rs852398698) in canine mammary tumors characteristics and progression. A group of 155 non-neutered bitches with mammary tumors was included in the study. Follow-up information was assessed 24 months after surgery.

Results

Genetic profiles associated with a later onset of mammary tumors and less aggressive clinicopathological features, namely smaller tumor size (≤ 3 cm) with extensive tubular differentiation and low canine-adapted prognostic index (vet-NPI), were identified in this study.

Conclusions

Our data suggest that theESR1genetic profile may help on the decision regarding the selection of individual tailored preventive measures against canine mammary tumors development, such as early neutering.
13C metabolic flux analysis on roles of malate transporter in lipid accumulation of Mucor circinelloides
Authors: Wang Lu , Zhang Huaiyuan , Zhang Yao , Song Yuanda
Published: September 2019

Background

Mitochondrial and cytoplasmic malate transporter proteins are responsible for transmembrane transport of malate, thereby linking malate metabolism in various subcellular regions of the cell. These transporters play an important role in fatty acid biosynthesis of oleaginous microorganisms. Our previous studies have found that lipid content of the recombinant Mucor circinelloides (M. circinelloides) strain with mitochondrial malate transporter (mt) gene overexpression was increased by 70%, while that of strain with mt gene knockout was decreased by 27%. However, the mechanism of malate transporter promoting the transport of mitochondrial malate and citrate related to lipid accumulation is not clear. Therefore, 13C-labeled glucose metabolic flux analysis was carried out to identify the metabolic network topology and estimate intracellular fluxes of genetically engineered M. circinelloides strains for the purpose of better understanding the roles of malate transporters in citrate transport systems and lipid accumulation.

Results

The metabolic flux distribution analysis suggested that tricarboxylic acid (TCA) cycle flux ratio of mt-overexpression strains was decreased compared to that of the control strain, but in contrast, glyoxylic acid (GOX) cycle flux ratio was increased. Accordingly, the mt-knockout strain showed an opposite phenomenon with a higher TCA cycle flux ratio and a lower GOX cycle flux ratio than the control strain. GOX cycle might be more effective than TCA cycle in producing malate and oxaloacetate replenishment. Moreover, a relatively higher flux ratio of the pentose phosphate (PP) pathway was obtained in mt-overexpression strains, but no significant difference in the malic enzyme flux between recombinant strains and the control strain. Our results confirmed that PP pathway might play an important role for supplying NADPH and malic enzyme is not a limiting factor for fatty acid synthesis in oleaginous fungus M. circinelloides strains.

Conclusion

Intracellular metabolic flux information suggested that mt-overexpression strains had higher flux in PP pathway and GOX cycle, lower flux in TCA cycle, and no difference in malic enzyme cycle. Together, the role of malate transporter was assumed to further participate in transporting cycle of acetyl-CoA and drive PP pathway to supply NADPH required for lipid accumulation in recombinant M. circinelloides strains.
Cell-type specific concentration regulation of the basal transcription factor TFIIH in XPBy/y mice model
Authors: Donnio Lise-Marie , Miquel Catherine , Vermeulen Wim , Giglia-Mari Giuseppina , Mari Pierre-Olivier
Published: September 2019

Background

The basal transcription/repair factor TFIIH is a ten sub-unit complex essential for RNA polymerase II (RNAP2) transcription initiation and DNA repair. In both these processes TFIIH acts as a DNA helix opener, required for promoter escape of RNAP2 in transcription initiation, and to set the stage for strand incision within the nucleotide excision repair (NER) pathway.

Methods

We used a knock-in mouse model that we generated and that endogenously expresses a fluorescent version of XPB (XPB-YFP). Using different microscopy, cellular biology and biochemistry approaches we quantified the steady state levels of this protein in different cells, and cells imbedded in tissues.

Results

Here we demonstrate, via confocal imaging of ex vivo tissues and cells derived from this mouse model, that TFIIH steady state levels are tightly regulated at the single cell level, thus keeping nuclear TFIIH concentrations remarkably constant in a cell type dependent manner. Moreover, we show that individual cellular TFIIH levels are proportional to the speed of mRNA production, hence to a cell’s transcriptional activity, which we can correlate to proliferation status. Importantly, cancer tissue presents a higher TFIIH than normal healthy tissues.

Conclusion

This study shows that TFIIH cellular concentration can be used as a bona-fide quantitative marker of transcriptional activity and cellular proliferation.
How does lesion size affect the pooled effect of traction-assisted endoscopic submucosal dissection on procedure time? A meta-regression
Authors: Cheng Sheng-Wei , Chang Chun-Chao , Su Ying-Fong , Kang Yi-No
Published: September 2019

The purpose of this letter was to explore how lesion size affects the pooled effect of traction-assisted endoscopic submucosal dissection on procedure time. Our meta-regression showed that lesion size negatively associated with the effect of traction-assisted endoscopic submucosal dissection on procedure time (estimate point = − 1.02; 95% confidence interval, from − 1.58 to − 0.46). We also confirmed this result in different statistical models including fixed effect regression and two mixed effects regression models.
Combination of electromagnetic navigation bronchoscopy-guided biopsy with a novel staining for peripheral pulmonary lesions
Authors: Qian Kai , Deng Yi , Shen Cheng , Feng Yong-Geng , Deng Bo , Tan Qun-You
Published: September 2019

Background

The diagnosis of peripheral pulmonary lesions (PPLs) is a challenging task for pulmonologists, especially for small PPLs. Conventional localization of these small PPLs, which are > 1 cm away from the visceral pleura in operation, is quite difficult. Currently used methods inevitably damage the visceral pleura and may cause a series of complications, such as pneumothorax and hemothorax. Hence, the present study aimed to find out an intraoperative localization method with no damage to the visceral pleura.

Methods

We retrospectively reviewed 21 patients with PLLs who underwent electromagnetic navigation bronchoscopy (ENB)-guided biopsy plus a new methylene blue staining with the help of massage (Massage Staining) in our department between August 2017 and December 2018.

Results

The median age of these 21 patients was 51.3 ± 2.1 years. The diameter of the PPLs was 8.2 ± 2.3 mm. The rate of successful biopsy was 76.2%, and the rate of excellent or satisfactory of Massage Staining was 81.0%, while all lesions of these 21 cases were included in the range of staining, and the median distance from the edge of the stained site to the edge of the lesion was 29 ± 18 mm. The duration of ENB-guided biopsy plus Massage Staining was 26.7 ± 5.3 min, and the intraoperative blood loss was 3.3 ± 1.5 ml. No pneumothorax, hemorrhage, and tracheal injury occurred intraoperatively.

Conclusions

The ENB-guided biopsy combined with Massage Staining is an innovative one-stop strategy designed to enhance the precision of thoracic surgery. The Massage Staining avoids damage to the visceral pleura, causes the low incidence of complications, but yields precise localization of PPLs.
White matter abnormalities of corpus callosum in patients with bipolar disorder and suicidal ideation
Authors: Zhang Ran , Jiang Xiaowei , Chang Miao , Wei Shengnan , Tang Yanqing , Wang Fei
Published: September 2019

Objective

Although many studies have shown that the corpus callosum (CC) may play an important role in bipolar disorder (BD) and suicide, the pathophysiological mechanism of BD underlying suicidal behavior is still unclear. This study aimed to explore the relationship between the CC, and BD and suicidal ideation using diffusion tensor imaging (DTI).

Method

A total of 203 participants (47 BD patients with suicidal ideation, 59 with BD without suicidal ideation, and 97 healthy controls [HC]) underwent DTI scanning at a single site. We examined the white matter integrity of the CC in the three groups.

Results

A comparison among groups showed that BD patients with suicidal ideation had significant lower fractional anisotropy (FA) values than those of BD without suicidal ideation and HCs in the body and genu of the CC, and FA values of BD without suicidal ideation were significantly lower than those of HCs. However, in the splenium of corpus callosum, no difference was found between BD without suicidal ideation and HCs.

Conclusions

Our findings add to the evidence suggesting that the CC plays a key role in BD with suicidal ideation, especially with respect to the role of the genu and body of the CC subserving emotion regulation.