bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico investigation of Y220C mutant p53 for lead design
Authors: Chowdhury Mayank Roy , Tiwari Anamika , Dubey G.P. 
Published: October 2019

Abstractp53 protein coded by the Tp53 gene is considered as one of the most intensively researched protein and mainly due to its role as a tumor suppressor, it acts as a tumor suppressor by carrying out two biologically complex processes namely Cell cycle arrest and apoptosis, In the oncogenic Y220C mutant p53, tyrosine is replaced by cysteine at 220th residue of the DNA binding Domain which causes the formation of a surface crevice, this specific mutation is responsible for approx. 100,000 cancer cases per year due to the destabilization and denaturation of the protein, as a result, the protein degrades at room temperature. In this work we carry out intensive Molecular Dynamic Simulations and Molecular Docking Studies to understand the structural dynamics of wild type p53 and changes the occurs in the mutant protein and also try to design lead against the druggable crevice and at the end of our study we used fragment-based optimization to come up with lead molecules which can act as scaffold for further drug development process
DNA Methylation Signature on Phosphatidylethanol, not Self-Reported Alcohol Consumption, Predicts Hazardous Alcohol Consumption in Two Distinct Populations
Authors: Liang Xiaoyu , Justice Amy C. , So-Armah Kaku , Krystal John H. , Sinha Rajita , Xu Ke 
Published: October 2019

ABSTRACTThe process of diagnosing hazardous alcohol drinking (HAD) is based on self-reported data and is thereby vulnerable to bias. There has been an interest in developing epigenetic biomarkers for HAD that might complement clinical assessment. Because alcohol consumption has been previously linked to DNA methylation (DNAm), here, we aimed to select DNAm signatures in blood to predict HAD from two demographically and clinically distinct populations (Ntotal=1,549). We first separately conducted an epigenome-wide association study (EWAS) for phosphatidylethanol (PEth), an objective measure of alcohol consumption, and for self-reported alcohol consumption in Cohort 1. We identified 102 PEth-associated CpGs, including 32 CpGs previously associated with alcohol consumption or alcohol use disorders. In contrast, no CpG reached epigenome-wide significance on self-reported alcohol consumption. Using a machine learning approach, two subsets of CpGs from EWAS on PEth and on self-reported alcohol consumption from Cohort 1 were separately tested for the prediction of HAD in Cohort 2. We found that a subset of 130 CpGs selected from the EWAS on PEth showed an excellent prediction of HAD with area under the ROC curve (AUC) of 91.31% in training set and 70.65% in validation set of Cohort 2. However, CpGs preselected from the EWAS on self-reported alcohol consumption showed a poor prediction of HAD with AUC 75.18% in the training set and 57.60% in the validation set. Our results demonstrate that an objective measure for alcohol consumption is a more informative phenotype than self-reported data for revealing epigenetic mechanism. The PEth-associated DNAm signature in blood is a robust biomarker for alcohol consumption.
Evaluating physicians’ serendipitous knowledge discovery in online discovery systems
Authors: Hopkins Mark E. , Zavalina Oksana L. 
Published: October 2019

Purpose
A new approach to investigate serendipitous knowledge discovery (SKD) of health information is developed and tested to evaluate the information flow-serendipitous knowledge discovery (IF-SKD) model. The purpose of this paper is to determine the degree to which IF-SKD reflects physicians’ information behaviour in a clinical setting and explore how the information system, Spark, designed to support physicians’ SKD, meets its goals.

Design/methodology/approach
The proposed pre-experimental study design employs an adapted version of the McCay-Peet’s (2013) and McCay-Peet et al.’s (2015) serendipitous digital environment (SDE) questionnaire research tool to address the complexity associated with defining the way in which SKD is understood and applied in system design. To test the IF-SKD model, the new data analysis approach combining confirmatory factor analysis, data imputation and Monte Carlo simulations was developed.

Findings
The piloting of the proposed novel analysis approach demonstrated that small sample information behaviour survey data can be meaningfully examined using a confirmatory factor analysis technique.

Research limitations/implications
This method allows to improve the reliability in measuring SKD and the generalisability of findings.

Originality/value
This paper makes an original contribution to developing and refining methods and tools of research into information-system-supported serendipitous discovery of information by health providers.
Administrative staff self-reported long-term conditions
Authors: Wright Kathy Lee , Verney Karen , Brennan Daryl , Lindsay David , Lindsay Daniel , Smyth Wendy 
Published: October 2019

Purpose
The purpose of this paper is to investigate the long-term conditions affecting the administration workforce of a regional Australian health service, and their self-management of these conditions.

Design/methodology/approach
A cross-sectional survey design was used. The sample consisted of all administration staff members employed in 2018 across a large regional health service in Northern Australia.

Findings
Of the 328 respondents, 167 (51 per cent) reported having at least one long-term condition. Of these, 136 (81.4 per cent) indicated a single main condition for which management strategies were used. Musculoskeletal conditions were the most commonly nominated category (59.6 per cent), followed by mental health (10.3 per cent). Respondents with musculoskeletal conditions were statistically more likely to have a co-existing mental health long-term condition, χ2(1) = 95.64, p<0.001. There was also a statistically significant association between respondents reporting a mental health condition and being overweight, χ2(1) = 54.27, p< 0.05.

Research limitations/implications
The response rate of 35 per cent, whilst relatively low, is a slight increase on similar surveys within this organisation. The reliability of the self-report data, presence of study bias and a weakening of the study’s external validity is acknowledged.

Practical implications
Targeted workplace intervention strategies, such as holistic wellness programs, should complement personal approaches, promote an ergonomic environment and create opportunities for increased dialogue between employees and their line managers, particularly regarding the complex interplay between long-term physical and mental health.

Originality/value
This is the first study of self-reported long-term conditions among administration staff within a health service, and augments findings from previous studies involving health professional groups in the same organisation.
Moisture absorption in thick composite plates: modelling and experiments
Authors: Canale Giacomo , Kinawy Moustafa , Sathujoda Prabhakar , Maligno Angelo , Citarella Roberto Guglielmo 
Published: October 2019

Purpose
When a thick structure is, on the contrary, subjected to moisture absorption, a fairly long time may be needed to reach full saturation. It is, therefore, important to understand and predict the areas of complex composite structures that are more prone to saturation. The material knock-down factors (proportional to the moisture content) may be applied only to these zones, in order to obtain a less pessimistic structural response prediction. The purpose of this paper is to investigate an FE diffusion model that was used to validate the absorption testing results of thick carbon epoxy laminates.

Design/methodology/approach
The experimental results were validated by using a diffusion model in Abaqus FE code.

Findings
The absorption results of three 15 mm thick carbon epoxy laminates are presented and reproduced via a mass diffusion model. The laminates were conditioned at 70°C and 85 per cent relative humidity in a moisture chamber. Areas more prone to saturation have been predicted by the FE model and the moisture content in the non-saturated areas has been calculated.

Practical implications
The practical implications of the absorption model are discussed on an example of an aero-engine fan blade-like structure.

Originality/value
Validation of thick panels’ absorption data is an important point of novelty of this paper, given the lack of experimental and modelling validation in the open literature.
Discrimination in the United States: Experiences of lesbian, gay, bisexual, transgender, and queer Americans
Authors: Casey Logan S. , Reisner Sari L. , Findling Mary G. , Blendon Robert J. , Benson John M. , Sayde Justin M. , Miller Carolyn 
Published: October 2019

AbstractObjectiveTo examine reported experiences of discrimination against lesbian, gay, bisexual, transgender, and queer (LGBTQ) adults in the United States, which broadly contribute to poor health outcomes.Data Source and Study DesignData came from a national, probability‐based telephone survey of US adults, including 489 LGBTQ adults (282 non‐Hispanic whites and 201 racial/ethnic minorities), conducted January‐April 2017.MethodsWe calculated the percentages of LGBTQ adults reporting experiences of discrimination in health care and several other domains related to their sexual orientation and, for transgender adults, gender identity. We report these results overall, by race/ethnicity, and among transgender adults only. We used multivariable models to estimate adjusted odds of discrimination between racial/ethnic minority and white LGBTQ respondents.Principal FindingsExperiences of interpersonal discrimination were common for LGBTQ adults, including slurs (57 percent), microaggressions (53 percent), sexual harassment (51 percent), violence (51 percent), and harassment regarding bathroom use (34 percent). More than one in six LGBTQ adults also reported avoiding health care due to anticipated discrimination (18 percent), including 22 percent of transgender adults, while 16 percent of LGBTQ adults reported discrimination in health care encounters. LGBTQ racial/ethnic minorities had statistically significantly higher odds than whites in reporting discrimination based on their LGBTQ identity when applying for jobs, when trying to vote or participate in politics, and interacting with the legal systemConclusionsDiscrimination is widely experienced by LGBTQ adults across health care and other domains, especially among racial/ethnic minorities. Policy and programmatic efforts are needed to reduce these negative experiences and their health impact on sexual and/or gender minority adults, particularly those who experience compounded forms of discrimination.
Association of adipokines with rheumatic disease activity indexes and periodontal disease in patients with early rheumatoid arthritis and their first‐degree relatives
Authors: Chaparro‐Sanabria Jeimy A. , Bautista‐Molano Wilson , Bello‐Gualtero Juan M. , Chila‐Moreno Lorena , Castillo Diana M. , Valle‐Oñate Rafael , Chalem Phillipe , Romero‐Sánchez Consuelo 
Published: October 2019

AbstractObjectiveTo evaluate the adipokine levels in early rheumatoid arthritis (eRA) and first‐degree relatives (FDR) of patients with RA and establish their association with rheumatic disease activity and periodontal variables.MethodA cross‐sectional study with eRA patients, FDR and a healthy population. Adipokine levels, clinical, joint radiological indexes and periodontal variables were evaluated. A descriptive, bivariate analysis was performed based on the adipokine levels by χ2, Fisher's test and Mann–Whitney U test. A logistic regression was made for associations.ResultsHigh leptin levels were associated with the diagnosis of eRA (odds ratio [OR] = 2.79; 95% CI 1.54‐5.07). Early rheumatoid arthritis with high adiponectin levels was less likely to have Multidimensional Health Assessment Questionnaire score >3, body mass index (BMI) >25 and Routine Assessment of Patient Index Data 3 score >12 (OR = 0.16; 95% CI 0.03‐0.72). Early rheumatoid arthritis was more likely to present high leptin and interleukin (IL)6 levels with low adiponectin simultaneously (OR = 5.03; 95% CI 1.05‐24.0). High leptin levels were associated with the FDR adjusted for IgG2 Porphyromonas gingivalis, swollen joints, P gingivalis and low IL6 (OR = 2.57; 95% CI 1.14‐5.95).ConclusionHigh adipokine levels in eRA may modulate the disease activity. Having more than 1 adipokine at high serum levels is associated with increased disability, disease activity and BMI, indicating that RA is controlled by adiponectin levels in the early stages of the disease. High leptin levels, presence of P gingivalis and swollen joints may be the factors associated with the development of RA in FDR.
Diffusion of effects of the ASSIST school‐based smoking prevention intervention to non‐participating family members: a secondary analysis of a randomized controlled trial
Authors: White James , Holliday Jo , Daniel Rhian , Campbell Rona , Moore Laurence 
Published: October 2019

AbstractAimsTo investigate whether effects of the ASSIST (A Stop Smoking In Schools Trial) school‐based smoking prevention intervention diffused from students to the people they lived with.DesignSecondary analysis of a cluster‐randomized control trial (cRCT).SettingEngland and Wales.ParticipantsA total of 10 730 students aged 12–13 years in 59 schools assigned using stratified block randomization to the control (29 schools, 5372 students) or intervention (30 schools, 5358 students) condition.Intervention and comparatorThe ASSIST intervention involves 2 days of off‐site training of influential students to encourage their peers not to smoke during a 10‐week period. The control group continued with their usual education.MeasurementsThe outcomes were the proportion of students who self‐reported living with a smoker and the smoking status of each resident family member/caregiver. Follow‐up assessments were immediately after the intervention and at 1 and 2 years post‐intervention.FindingsThe odds ratio (OR) for living with a smoker in the intervention compared with the control groups was 0.86 [95% confidence interval (CI) = 0.72, 1.03] immediately after the intervention, OR = 0.84 (95% CI = 0.72, 0.97) at a 1‐year follow‐up and OR = 0.86 (95% CI = 0.75, 0.99) at 2‐year follow‐up. In a three‐tier multi‐level model with data from all three follow‐ups, student‐reported smoking by fathers (OR = 0.90, 95% CI = 0.80, 1.00), brothers (OR = 0.78, 95% CI = 0.67, 0.92) and sisters (OR = 0.80, 95% CI = 0.69, 0.92) was lower in the intervention compared with control group. Subgroup analyses by baseline smoking status suggested that these effects were more consistent with prevention of uptake than prompting cessation.ConclusionsA Stop Smoking In Schools Trial (ASSIST) school‐based smoking prevention intervention may have reduced the prevalence of smoking in people who lived with ASSIST‐trained students. This indirect transmission is consistent with the predictions of diffusion of innovations theory which underpins the design of ASSIST.
Substance use disorders and risk for treatment resistant depression: a population‐based, nested case‐control study
Authors: Brenner Philip , Brandt Lena , Li Gang , DiBernardo Allitia , Bodén Robert , Reutfors Johan 
Published: October 2019

AbstractBackground and aimsTreatment‐resistant depression (TRD), defined as inadequate treatment response after at least two adequate treatment trials, is common among patients initiating antidepressant treatment. Current or previous substance use disorders (SUD) are common among patients with depression and often lead to worse treatment outcomes. However, in clinical studies, SUD have not been found to increase the risk for TRD. The aim of this study was to investigate the association between SUD and TRD.DesignNested case–control study.SettingNation‐wide governmental health‐care registers in Sweden.Cases and controlsData on prescribed drugs and diagnoses from specialized health care were used to establish a prospectively followed cohort of antidepressant initiators with depression (n = 121 669) from 2006 to 2014. Of these, 15 631 patients (13%) were defined as TRD cases, with at least three treatment trials within a single depressive episode. Each case with TRD was matched on socio‐demographic data with five controls with depression.MeasurementsCrude and adjusted odds ratios (aOR) with 95% confidence intervals (CI) estimated the association between TRD and SUD diagnosis and/or treatment in five different time intervals until the time for fulfillment of TRD definition for the case. The analysis was adjusted for clinical and socio‐demographic covariates.FindingsHaving any SUD during, or ≤ 180 days before start of, antidepressant treatment was associated with almost double the risk for TRD [≤ 180 days before: adjusted OR (aOR) = 1.86, CI = 1.70–2.05]. Increased risks for TRD were found ≤ 180 days before treatment start for the subcategories of sedative use (aOR = 2.37; 1.88–2.99), opioids (aOR = 2.02; 1.48–2.75), alcohol (aOR = 1.77; CI = 1.59–1.98) and combined substance use (aOR = 2.31; 1.87–2.99).ConclusionsRecent or current substance use disorders is positively associated with treatment resistance among patients initiating treatment for depression.
New psychoactive substances (NPS) in the Netherlands: occurrence in forensic drug samples, consumer drug samples and poisons center exposures between 2013 and 2017
Authors: Hondebrink Laura , Nugteren‐van Lonkhuyzen Johanna J. , Hunault Claudine C. , van den Berg Jorrit , van der Gouwe Daan , van Riel Antoinette J. H. P. 
Published: October 2019

AbstractBackground and AimsAlthough European‐wide data on the new psychoactive substances (NPS) drug market are available, country‐specific data are limited. We studied recent NPS trend data relative to all recreational drugs on the Dutch drug market.DesignNational observational study.SettingThe Netherlands.Data sourcesThree national indicators were used between 2013 and 2017: (1) forensic drug samples offered to the Netherlands Forensic Institute (NFI); (2) drug samples submitted by consumers to the Drugs Information and Monitoring System (DIMS); and (3) exposures in which the Dutch Poisons Information Center (DPIC) was consulted.MeasurementsOverall NPS incidence rate was the primary outcome. Numbers and specific categories of NPS were also studied. Changes in NPS incidence rates over time were analyzed using Poisson regression analyses [year effect expressed as incidence rate ratios (IRR)].FindingsFrom 2013 to 2017, NPS were involved in 1892 forensic samples, 6316 consumer samples and 481 poisons center exposures. In 2013, NPS incidence rates were 2.5, 7 and 4% versus 3, 11 and 11% in 2017, respectively, in the NFI, DIMS and DPIC samples/exposures. NPS incidence rates increased significantly in consumer samples between 2013 and 2016 [IRR = 1.23; 95% confidence interval (CI) = 1.18, 1.29] and in poisons center exposures between 2013 and 2017 (IRR = 1.19; 95% CI = 1.06, 1.35), while the trend in forensic samples appeared more stable. Phenethylamines were the largest class and were detected in 58, 80 and 63% of NFI, DIMS and DPIC samples/exposures, respectively. Detected phenethylamines mainly involved 4‐fluoroamphetamine and 2C‐x derivatives. The second largest class were cathinones, which were detected in 21, 11 and 16% of NFI, DIMS and DPIC samples/exposures, respectively.ConclusionsAnalysis of forensic drug samples, consumer drug samples and exposures reported to poison centers from 2013 to 2017 shows the constant presence of new psychoactive substances on the Dutch drug market and its use by the Dutch population. The two largest classes present in the Netherlands were phenethylamines and cathinones.
Acute post‐streptococcal glomerulonephritis in Central Australia
Authors: Dowler James , Wilson Angela 
Published: October 2019

AbstractObjectiveTo determine the incidence, clinical presentation and progress of acute post‐streptococcal glomerulonephritis in Central Australia.DesignRetrospective observational analysis.SettingPaediatric inpatient admission at Alice Springs Hospital.ParticipantsPatients admitted to Alice Springs Hospital under 14 years of age meeting diagnostic criteria for acute post‐streptococcal glomerulonephritis between January 2010 and December 2014.Main Outcome MeasuresIncidence of acute post‐streptococcal glomerulonephritis in central Australia. Biochemical abnormalities associated with acute post‐streptococcal glomerulonephritis. Co‐occuring conditions.ResultsSixty‐nine out of the 174 cases reviewed were identified as having either acute post‐streptococcal glomerulonephritis (63) or probable acute post‐streptococcal glomerulonephritis (6). We calculate the incidence of APSGN admission to be higher than previously reported and the highest reported incidence globally in children. Clinical evidence of skin infection was frequently documented. Co‐occurring infections were common, including scabies/head lice, urinary tract infection and pneumonia. Fifty‐three patients showed biochemical evidence of acute kidney injury.ConclusionsAboriginal children in Central Australia have the highest incidence of acute post‐streptococcal glomerulonephritis reported worldwide. Urgent action is required to improve housing and reduce overcrowding in Central Australian towns and communities to reduce the burden of disease of skin infection and Group A Streptococcus related diseases. Without effective change in living conditions, it is unlikely that there will be a significant change in the morbidity related to these conditions.
Investigating the clinical factors and comedications associated with circulating levels of atorvastatin and its major metabolites in secondary prevention
Authors: Turner Richard M. , Fontana Vanessa , FitzGerald Richard , Morris Andrew P. , Pirmohamed Munir 
Published: October 2019

AimsThe lipid‐lowering drug, atorvastatin (ATV), is 1 of the most commonly prescribed medications worldwide. The aim of this study was to comprehensively investigate and characterise the clinical factors and comedications associated with circulating levels of ATV and its metabolites in secondary prevention clinical practice.MethodsThe plasma concentrations of ATV, 2‐hydroxy (2‐OH) ATV, ATV lactone (ATV L) and 2‐OH ATV L were determined in patients 1 month after hospitalisation for a non‐ST elevation acute coronary syndrome. Factors were identified using all subsets multivariable regression and model averaging with the Bayesian information criterion. Exploratory genotype‐stratified analyses were conducted using ABCG2 rs2231142 (Q141K) and CYP2C19 metaboliser status to further investigate novel associations.ResultsA total of 571 patients were included; 534 and 37 were taking ATV 80 mg and 40 mg daily, respectively. Clinical factors associated with ATV and/or its metabolite levels included age, sex, body mass index and CYP3A inhibiting comedications. Smoking was newly associated with increased ATV lactonisation and reduced hydroxylation. Proton pump inhibitors (PPIs) and loop diuretics were newly associated with modestly increased levels of ATV (14% and 38%, respectively) and its metabolites. An interaction between PPIs and CYP2C19 metaboliser status on exposure to specific ATV analytes (e.g. interaction P = .0071 for 2‐OH ATV L) was observed. Overall model R2 values were 0.14–0.24.ConclusionMultiple factors were associated with circulating ATV and metabolite levels, including novel associations with smoking and drug–drug(–gene) interactions involving PPIs and loop diuretics. Further investigations are needed to identify additional factors that influence ATV exposure.