bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the electronic prescription as a method of measurement of treatment adherence in hypertension
Authors: Marquez-Contreras Emilio , López  García-Ramos Lourdes , Martell-Claros Nieves , Gil-Guillen Vicente F , Márquez-Rivero Sara , Pérez-López Elena , Garrido-Lopez Maria Angeles , Farauste Celia , Lopez-Pineda Adriana , Casado-Martínez Jose Joaquín , Carratala-Munuera Concepcion 
Published: January 2018

Background. The diagnosis of non-adherence is complex and there are no completely reliable methods that can be used widely in daily practice. The aim of this study was to validate electronic prescriptions as a method of measuring treatment adherence in patients with mild-moderate hypertension.
Methods. We conducted a prospective, longitudinal, multicenter study in primary care centers. The study involved 120 patients treated for hypertension and included in the electronic prescription program of the centers. Five visits were made: initial, 6, 12, 18 and 24 months. Adherence was measured using an electronic monitor [medication event monitoring system (MEMS)] and through the electronic prescription program. We calculated the adherence rate (AR) using the MEMS and the electronic prescriptions, with the Medication Possession Ratio (MPR). Adherent patients were considered to be those whose AR was 80-100%. To validate the electronic prescription, its data were compared to the pill count by MEMS (Method of certainty). Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, and positive (LR+) and negative (LR-) likelihood ratios were calculated. The Kappa concordance index and the area under the ROC curve were also determined.
Results. The study was completed by 108 patients (mean age 61.06 years, SD 9.08). Adherence was 77.4% by MEMS (95% CI: 66.8-88%) and 80.4% (95% CI=70.3-90.5) by MPR. At 24 months the sensitivity was 87%, specificity 93.7%, PPV 80%, NPV 96.1%, LR+ 13.8 and LR- 0.1. The K was 0.782 and the AUC was 0.903 (95% CI: 0.817-0.989). Therapeutic complexity was associated with pharmacological non-adherence (OR=1.35, p<0.01).
Discussion. The electronic prescription was an excellent method to measure non-adherence in hypertensive patients included in this program for over two years. Therapeutic simplicity improved treatment adherence.
Identification of bladder cancer biomarkers by genomic approaches
Authors: Majewski Tadeusz , Bondaruk Jolanta , Lee Sangkyou , Lee June Goo , Baggerly Keitg , McConkey David , Czerniak Bogdan 
Published: January 2018

Bladder Cancer is one of the most frequent human cancer which develops on two tracks, papillary and non-papillary that correspond to clinically different forms of the disease. Most bladder cancers are chemically induced with tobacco smoking being the leading risk factor. Recent advances of bladder cancer research for which our laboratory has significantly contributed have enhanced the understanding of the origin of bladder cancer from urothelial progenitor cells via field effects along papillary/luminal non-papillary/basal pathways. Here we present the contribution to the development of novel, both diagnostic and therapeutic, biomarkers using genomic high throughput technologies.
The analysis of hits associated with growth advantage of preneoplastic lesions allowed us to identify six chromosomal regions mapping 3q22, 5q22.2-5q23.3, 9q22.12, 10q26.1, 13q14 and 17p13 that may be critical for the development of bladder cancer and contain a distinct class of genes referred to us forerunner (FR) genes involved in the clonal expansion of precursor conditions. We concentrated our efforts on one of these regions; which contain a model tumor suppressor RB1. We used high-resolution whole-organ mapping with SNPs, which facilitated the identification of five positional candidate FR genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11) mapping contiguously to RB1. We hypothesized that identification of novel forerunner genes and the investigation in early occult phases of human bladder preneoplasia may not only provide important mechanistic clues to the development of human cancer but also identify a novel class of early detection markers capable of detecting the clinically and microscopically occult phases of human cancer development.
We used the whole-organ histologic and genetic mapping strategy coupled with next generation whole exome sequencing using complemented with genotyping using Illumina HumanOmni2.5_8 chips and whole genome methylation analyses to define the molecular alterations that were associated with the progression of muscle-invasive bladder cancer in one surgical specimen.
We identified a total of 18 structurally significant mutations, three of which appeared to be clear "driver" mutations that had been annotated previously. Alterations in chromatin hyper- and hypomethylation predominated in all of the regions that contained normal-appearing urothelium or low-grade dysplasia. In total, 31 genes were hypermethylated and 26 genes were hypomethylated. Copy number alterations were numerous (n=242) in areas that contained high-grade dysplasia suggesting that genomic instability proceeded the emergence of driver mutations in what ultimately emerged as the dominant tumor subclone. Chromosomal gains (n=216) vastly outnumbered losses (n=26).
Data reuse and the open data citation advantage
Authors: Piwowar Heather , Vision Todd J 
Published: January 2018

BACKGROUND: Attribution to the original contributor upon reuse of published data is important both as a reward for data creators and to document the provenance of research findings. Previous studies have found that papers with publicly available datasets receive a higher number of citations than similar studies without available data. However, few previous analyses have had the statistical power to control for the many variables known to predict citation rate, which has led to uncertain estimates of the “citation boost”. Furthermore, little is known about patterns in data reuse over time and across datasets.
METHOD AND RESULTS: Here, we look at citation rates while controlling for many known citation predictors, and investigate the variability of data reuse. In a multivariate regression on 10,555 studies that created gene expression microarray data, we found that studies that made data available in a public repository received 9% (95% confidence interval: 5% to 13%) more citations than similar studies for which the data was not made available. Date of publication, journal impact factor, open access status, number of authors, first and last author publication history, corresponding author country, institution citation history, and study topic were included as covariates. The citation boost varied with date of dataset deposition: a citation boost was most clear for papers published in 2004 and 2005, at about 30%. Authors published most papers using their own datasets within two years of their first publication on the dataset, whereas data reuse papers published by third-party investigators continued to accumulate for at least six years. To study patterns of data reuse directly, we compiled 9,724 instances of third party data reuse via mention of GEO or ArrayExpress accession numbers in the full text of papers. The level of third-party data use was high: for 100 datasets deposited in year 0, we estimated that 40 papers in PubMed reused a dataset by year 2, 100 by year 4, and more than 150 data reuse papers had been published by year 5. Data reuse was distributed across a broad base of datasets: a very conservative estimate found that 20% of the datasets deposited between 2003 and 2007 had been reused at least once by third parties.
CONCLUSION: After accounting for other factors affecting citation rate, we find a robust citation benefit from open data, although a smaller one than previously reported. We conclude there is a direct effect of third-party data reuse that persists for years beyond the time when researchers have published most of the papers reusing their own data. Other factors that may also contribute to the citation boost are considered. We further conclude that, at least for gene expression microarray data, a substantial fraction of archived datasets are reused, and that the intensity of dataset reuse has been steadily increasing since 2003.
Dose dependent role of Emodin and BTB14431 in suspension colon cancer model in rats
Authors: Rogalla Stephan , Pohlenz Jana , Garcia Vanessa , Koplin Gerold , Fuehrer Kirsten , Lun Andreas , Dubiel Wolfgang , Geier Caroline F. , Braumann Chris 
Published: January 2018

Background. An “In Silico 2D/3D Conformer Screening” for structural similar antitumor substances to Curcumin was carried out and the novel antrachinone BTB14431 was found. Emodin, contained in several Chinese medical plants and BTB14431 are known to be potential inhibitors of the COP9-signalosome - stabilizing the tumor suppressor protein p53. The aim of this study was to analyze the suppressing effects on colorectal cancer in a standardized rat model (WAG/Rij).
Methods. A suspension of CC531 colon cancer cells was applied to the cecum after laparotomy and, additionally, at the back of animals. Therapy was conducted twice daily for 7 days, with increasing doses of BTB14431, Emodin and with isotone sodium chloride solution (control) intravenously (iv) or intraperitoneally (ip). Therapy was initiated the day of tumor cell application. Peripheral blood samples were taken before surgery and on day 7. 21 days after the end of therapy, the animals were euthanized and tumor growth was evaluated.
Results. Data showed a downward trend of the total tumor growth after iv and ip treatment with low doses of BTB14431 and Emodin. Differential blood analysis showed apoptosis, but no major changes in hemogram. Increasing doses of Emodin elevated total mortality rate exponentially.
Conclusions.Although apoptosis was verified, no significant tumor suppressing effects could be observed for iv and ip treatment of both agents in our model. This stays in contrast to former in vitro studies. Agents remain viable novel substances. They will be the subject of upcoming studies. Additional data is needed to evaluate the significance of the “In Silico Screening” to identify potential in vivo anti-tumor drugs.
Psychosocial determinants of antenatal anxiety and depression in Pakistan: Is social support a mediator?
Authors: Waqas Ahmed , Raza Nahal , Wajid Lodhi Haneen , Muhammad Zerwah , Jamal Mehak , Suleman Abdul Rehman 
Published: January 2018

Introduction: Pregnancy is generally viewed as a time of fulfillment and joy; however, for many women it can be a stressful event. In South Asia it is associated with cultural stigmas revolving around gender discrimination, abnormal births and genetic abnormalities. It is also associated with several psychiatric problems in women, most notably depression and anxiety.
Methodology: This cross-sectional study was done at four teaching hospitals in Lahore from February, 2014 to June, 2014. A total of 500 pregnant women seen at hospital obstetrics and gynecology departments were interviewed with a questionnaire consisting of three sections: demographics, the Hospital Anxiety and Depression Scale (HADS) and the Social Provisions Scale (SPS). All data were analyzed with SPSS v. 20. Descriptive statistics were analyzed for demographic variables. Pearson’s chi-squared test, bivariate correlations and multiple linear regression were used to analyze associations between the independent variables and scores on the HADS and SPS.
Results: Mean age among the 500 respondents was 27.41 years (5.65). Anxiety levels in participants were categorized as normal (145 women, 29%), borderline (110, 22%) or anxious (245, 49%). Depression levels were categorized as normal (218 women, 43.6%), borderline (123, 24.6%) or depressed (159, 31.8%). Inferential analysis revealed that higher HADS scores were significantly associated with lower scores on the SPS, rural background, history of harassment, abortion, cesarean delivery and unplanned pregnancies (P < .05). Social support (SPS score) mediated the relationship between the total number of children, gender of previous children and HADS score. Women with more daughters were significantly more likely to score higher on the HADS and lower on the SPS, whereas higher numbers of sons were associated with the opposite trends in the scores (P < .05)
Conclusion: Because of the predominantly patriarchal sociocultural context in Pakistan, the predictors of antenatal anxiety and depression may differ from those in developed countries. Rural women and working women had higher levels of antenatal anxiety and depression, which contradicts earlier findings in western countries. Our study found that higher numbers of daughters were associated with higher levels of depression and anxiety, whereas sons had a protective influence. We therefore suggest that interventions designed and implemented to reduce antenatal anxiety and depression should take into account these unique factors operating in developing countries and patriarchal societies.
Ranking small molecules by how much they preferentially inhibit the growth of cancer cell lines with either BRAF or KRAS oncogene mutations
Authors: Langham James 
Published: January 2018

We were interested in the question of whether it might be possible to use knowledge of cancer-related mutations in the cell lines of the NCI60 screening data set to identify small molecules that preferentially inhibit the growth of cell lines containing either BRAF or KRAS oncogene mutations. Our hypothesis was that this cell line mutation knowledge could help to identify small molecules that were more likely to preferentially inhibit growth of cell lines with a particular mutation. It seems that any such molecules might be further investigated to try to better understand the molecular mechanisms of growth inhibition.
We defined a quantity, \(\text{Diff}_{\text{mut}}\), that estimates how much more a given small molecule inhibits cell lines with a mutation of interest than cell lines without that mutation. We ranked the small molecules in descending order of \(\text{Diff}_{\text{mut}}\) and then tried to explain whether the ranking of the highest ranked molecules made sense in terms of independent facts about these molecules.
This method showed the BRAF inhibitor vemurafenib to be highly ranked in the BRAF ranking. The cytidine analog cytarabine was found to be highly ranked in the KRAS ranking. Other cytidine analogs were also found to be highly ranked with respect to KRAS.
Attitudes of medical students in Pakistan toward the doctor-patient relationship
Authors: Ahmad Waqas , Krupat Edward , Asmaa Yumna , Fatima Noor-E- , Attique Rayan , Mahmood Umar 
Published: January 2018

Background. We initiated this study with the aim to assess the leaning of medical students towards either a doctor-centered or a patient-centered care and explore the effects of personal attributes on it like gender, academic year etc. of the students.
Methods. A cross-sectional study was conducted between July-Sep 2013. The study population consisted of 1274 medical students in years 1-5 from two medical colleges. English version of PPOS was used to assess attitudes of medical students towards doctor-patient relationship. The relationship between PPOS scores and individual characteristics like gender, academic year etc. were examined by using Independent t-test and one way ANOVA.
Results. A total of 792 students formed the final sample. Characteristics associated with most patient-centered attitudes were being in 4th academic year, married, being a foreigner and belonging to a Private college (p<0.05). Characteristics associated with most doctor-centered attitudes were being in 2nd academic year, divorced, having a local origin and belonging to a Govt. college (p<0.05). Gender and having doctor parents had no bearing, statistically, on the attitudes.
Conclusion. Despite ongoing debate and emphasis on a patient-centered curriculum, our study suggests that current curriculum and its teachings are not producing the results they are designed to achieve. Students should be adequately exposed to the patients from the beginning of their medical education in clinical settings which are more sympathetic to a patient-centered care.
Understanding the context for pet obesity; self-reported beliefs and factors influencing pet feeding and exercise behaviour among pet owners
Authors: Downes Martin J , Devitt Catherine , Downes Marie , More Simon J 
Published: January 2018

Pet obesity contributes to increased risk of various diseases, such as cancer and diabetes mellitus as well as worsening of orthopaedic problems, and a reduction in survival rate. Changes in feeding regimes and increased amounts of exercise have been an important component of weight management programs. This study identifies the self-reported beliefs and factors that influence owner behaviour around feeding and exercising their pet. Pet owners were recruited through six different private veterinary practices (three city practices; two in regional towns; and one in a rural area).
Seven focus groups were conducted with 43 participants in total. Feeding one’s pet is influenced by beliefs about pet specific needs and pet food and pet health, pet owners’ perceived control over the feeding regime, and the implications for feeding for the pet owner. Treats are used in the absence of owner control over pet begging and emotional attachment, and to influence pet behaviour. Pet exercise is influenced by beliefs about pet specific exercise needs, and the implications of exercising one’s pet for the pet owner.
Beliefs, and barriers to appropriate feeding and exercise are useful in explaining pet owners’ behaviour and are; associated with the level of control over the feeding regime, control relating to pet behaviour, and the perceived ease of feeding and exercise. Understanding owner behaviours on feeding and exercise allows for a more targeted approach to preventing and treating pet obesity.
Pooling morphometric estimates: a statistical equivalence approach
Authors: Pardoe Heath R , Cutter Gary , Alter Rachel A , Kucharsky Hiess Rebecca , Semmelroch Mira , Parker Donna , Farquharson Shawna , Jackson Graeme , Kuzniecky Ruben 
Published: January 2018

Changes in hardware or image processing settings are a common issue for large multi-center studies. In order to pool MRI data acquired under these changed conditions, it is necessary to demonstrate that the changes do not affect MRI-based measurements. In these circumstances classical inference testing is inappropriate because it is designed to detect differences, not prove similarity. We used a method known as statistical equivalence testing to address this limitation.
Equivalence testing was carried out on three datasets: (i) cortical thickness and automated hippocampal volume estimates obtained from healthy individuals imaged using different multi-channel head coils; (ii) manual hippocampal volumetry obtained using two readers; and (iii) corpus callosum area estimates obtained using an automated method with manual cleanup carried out by two readers. Equivalence testing was carried out using the “two one-sided tests” (TOST) approach. Power analyses of the two one-sided tests were used to estimate sample sizes required for well-powered equivalence testing analyses. Mean and standard deviation estimates from the automated hippocampal volume dataset were used to carry out an example power analysis.
Cortical thickness values were found to be equivalent over 61% of the cortex when different head coils were used (q < 0.05, FDR correction). Automated hippocampal volume estimates obtained using the same two coils were statistically equivalent (TOST p = 4.28 × 10-15). Manual hippocampal volume estimates obtained using two readers were not statistically equivalent (TOST p = 0.97). The use of different readers to carry out limited correction of automated corpus callosum segmentations yielded equivalent area estimates (TOST p = 1.28 × 10-14). Power analysis of simulated and automated hippocampal volume data demonstrated that the equivalence margin affects the number of subjects required for well-powered equivalence tests.
We have presented a statistical method for determining if morphometric measures obtained under variable conditions can be pooled. The equivalence testing technique is applicable for analyses in which experimental conditions vary over the course of the study.
Diversification patterns based on the largest morphological phylogenetic analysis of Pleurodira
Authors: Ferreira Gabriel S , Sterli Juliana , Bronzati Filho Mario , Langer Max C 
Published: January 2018

Background. Most studies on pleurodiran turtles are about the behavior and/or feeding habits analyzes, description of new taxa or specimens (both extinct and extant), or phylogenetic analyzes of one of its subclades with extant taxa: Chelidae, Pelomedusidae or Podocnemididae. With the exception of some molecular phylogenies, there are no phylogenetic analyses of extant and extinct representatives of Pleurodira including all of its lineages. A broader understanding of the evolutionary history of Pleurodira requires a phylogenetic hypothesis based on more extensive taxonomic and character samplings.Methods. We constructed a taxon-character matrix including 227 morphological characters and 87 taxa from all the Pleurodira lineages, plus one stem Pan-Pleurodira, Notoemys laticentralis, and one stem-Testudinata, Proganochelys quenstedti, as outgroups. The resulting matrix was analyzed using parsimony, Tree Bisection and Reconnection (TBR) algorithms, with 5000 replicates, and a hold of 20. The obtained strict consensus tree was used as the basis of a diversification analysis using topology-based methods. A nestedgrowing tree approach was employed to create a corresponding tree for different intervals of the geological history of the group. Six distinct time bins were created for periods in which members of Pleurodira occur: Early Cretaceous, Late Cretaceous, Paleocene, Eocene, Miocene, and Recent.
Results. All main pleurodiran clades were recovered in the strict consensus tree, but with some changes in their relationship compared to previous analyses, e.g. the inclusiveness of both Pelomedusoides and Bothremydidae. The diversification analysis shows that, after the establishment of the two major lineages (i.e. Chelidae and Pelomedusoides) in the Early Cretaceous, these subgroups diversified in distinct rates along their evolutionary history. Two main diversification shifts were identified: one at the early evolution of Podocnemoidea, during the Late Cretaceous, and another during the Miocene, deep nested in the Podocnemididae clade.
Discussion. The resulting strict consensus tree is the largest exclusive phylogenetic hypothesis for Pleurodira, including both extant and extinct taxa. Based on morphological data, it allows more inclusive inferences on the general morphological and diversification patterns of the group. The diversification pulses analysis suggests variation on the rates of diversification on the different pleurodiran clades. The first shift detected is related to the great radiation of Bothremydidae and Podocnemoidae in the Late Cretaceous; the second shift, detected in the Miocene, is related to a diversification within the Stereogenyina, a Podocnemididae clade. Ongoing analysis will determine which factors could enforce those different diversification rates in the evolution of Pleurodira.