bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxicity of Vincristine Combined With Posaconazole in Children With Acute Lymphoblastic Leukemia
Authors: Pekpak Esra , İleri Talia , İnce Elif , Ertem Mehmet , Uysal Zümrüt 
Published: December 2017

Background:Vincristine (VCR) is one of the main drugs of acute lymphoblastic leukemia (ALL) treatment. Azole antifungal medications are used for treatment or prophylaxis of invasive fungal infections in acute leukemia. Coadministration of these drugs increases the risk of VCR toxicity.Observations:We presented a girl with ALL using posaconazole prophylaxis. She developed VCR toxicity that included tubulopathy, high blood pressure, neuropathic pain, difficulty walking, diffuse muscular weakness, constipation, abdominal pain.Conclusions:There are limited data in children with ALL for posaconazole prophylaxis. We recommend that VCR side effects should be evaluated by careful monitoring of the patients who are on this combination therapy.
Medical Versus Surgical Approach to Initial Treatment in Septic Arthritis
Authors: Flores-Robles Bryan Josué , Jiménez Palop Mercedes , Sanabria Sanchinel Abel Alejandro , Andrus Robert Francis , Royuela Vicente Ana , Sanz Pérez Marta Isabel , Espinosa Malpartida María , Ramos Giráldez Consuelo , Merino Argumanez Carolina , Villa Alcázar Luis Fernando , Andréu Sánchez José Luis , Godoy Tundidor Hildegarda , Campos Esteban José , Sanz Sanz Jesús , Barbadillo Mateos Carmen , Isasi Zaragoza Carlos , Mulero Mendoza Juan 
Published: December 2017

Objective
The aim of this study was to compare the functional results of 2 different procedure types, medical or surgical used in treating native joint septic arthritis.

Methods
In this cohort study, we reviewed the clinical registries of patients admitted to a single third-level hospital with the diagnosis of septic arthritis during the period of January 1, 2008, to January 31, 2016.

Results
A total of 63 cases of septic arthritis were identified in which the initial approach for 49 patients was medical (arthrocentesis), whereas the initial approach for 14 patients was surgical (arthroscopy or arthrotomy). Of the 49 patients who received initial medical treatment (IMT), 15 patients (30%) later required surgical treatment because of poor progress. The median age of the patients was 60 (SD, 18) years. The group who received IMT were older than those who received initial surgical treatment (median, 64 years [interquartile range {IQR}, 54–76 years], vs. 48 years [IQR, 30–60 years]). There was a larger percentage of male patients in the surgical group (78% vs. 42% [p = 0.018]). Thirty percent of the medical group had been receiving corticosteroid treatment (p = 0.018). Results of complete recovery of joint functionality showed no significant differences after 1 year (68% with MT vs. 67% with ST, p = 0.91). Both groups had similar symptom duration until diagnosis, duration of antibiotic therapy (median, 30 days [IQR, 28–49 days], vs. 29.5 days [IQR, 27–49] days), and mortality rate (3 in the medical group).

Conclusions
The results of the study show that initial surgical treatment in patients with native joint septic arthritis is not superior to IMT. However, half of the patients with shoulder and hip infections treated with IMT eventually required surgical intervention, suggesting that perhaps this should be the preferred initial approach in these cases.
Relaxivity of Ferumoxytol at 1.5 T and 3.0 T
Authors: Knobloch Gesine , Colgan Timothy , Wiens Curtis N. , Wang Xiaoke , Schubert Tilman , Hernando Diego , Sharma Samir D. , Reeder Scott B. 
Published: December 2017

ObjectivesThe aim of this study was to determine the relaxation properties of ferumoxytol, an off-label alternative to gadolinium-based contrast agents, under physiological conditions at 1.5 T and 3.0 T.Materials and MethodsFerumoxytol was diluted in gradually increasing concentrations (0.26–4.2 mM) in saline, human plasma, and human whole blood. Magnetic resonance relaxometry was performed at 37°C at 1.5 T and 3.0 T. Longitudinal and transverse relaxation rate constants (R1, R2, R2*) were measured as a function of ferumoxytol concentration, and relaxivities (r1, r2, r2*) were calculated.ResultsA linear dependence of R1, R2, and R2* on ferumoxytol concentration was found in saline and plasma with lower R1 values at 3.0 T and similar R2 and R2* values at 1.5 T and 3.0 T (1.5 T: r1saline= 19.9 ± 2.3 s−1mM−1; r1plasma= 19.0 ± 1.7 s−1mM−1; r2saline= 60.8 ± 3.8 s−1mM−1; r2plasma= 64.9 ± 1.8 s−1mM−1; r2*saline= 60.4 ± 4.7 s−1mM−1; r2*plasma= 64.4 ± 2.5 s−1mM−1; 3.0 T: r1saline= 10.0 ± 0.3 s−1mM−1; r1plasma= 9.5 ± 0.2 s−1mM−1; r2saline= 62.3 ± 3.7 s−1mM−1; r2plasma= 65.2 ± 1.8 s−1mM−1; r2*saline= 57.0 ± 4.7 s−1mM−1; r2*plasma= 55.7 ± 4.4 s−1mM−1). The dependence of relaxation rates on concentration in blood was nonlinear. Formulas from second-order polynomial fittings of the relaxation rates were calculated to characterize the relationship between R1bloodand R2bloodwith ferumoxytol.ConclusionsFerumoxytol demonstrates strong longitudinal and transverse relaxivities. Awareness of the nonlinear relaxation behavior of ferumoxytol in blood is important for ferumoxytol-enhanced magnetic resonance imaging applications and for protocol optimization.
Computed Tomography Features associated With the Eighth Edition TNM Stage Classification for Thymic Epithelial Tumors
Authors: Padda Sukhmani K. , Terrone Donato , Tian Lu , Khuong Amanda , Neal Joel W. , Riess Jonathan W. , Berry Mark F. , Hoang Chuong D. , Burt Bryan M. , Leung Ann N. , Schwartz Erich J. , Shrager Joseph B. , Wakelee Heather A. 
Published: December 2017

Purpose:
The eighth edition of the TNM classification of malignant tumors for the first time includes an official staging system for thymic epithelial tumors (TETs) recognized by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). Staging is critical for the management of TETs, and determining stage accurately from imaging has the potential to improve clinical outcomes. We examine preoperative computed tomography (CT) characteristics of TETs associated with AJCC/UICC pathologic TNM stage.

Materials and Methods:
In this retrospective study, patients were included if they met all the following criteria: (1) diagnosis of TET, (2) had primary curative intent surgery performed at Stanford University, and (3) had available preoperative CT imaging for review. Tumor pathology was staged according to the eighth edition TNM classification. Fifteen CT scan features were examined from each patient case according to the International Thymic Malignancy Interest Group standard report terms in a blinded manner. A Lasso-regularized multivariate model was used to produce a weighted scoring system predictive of pathologic TNM stage.

Results:
Examining the 54 patients included, the following CT characteristics were associated with higher pathologic TNM stage when using the following scoring system: elevated hemidiaphragm (score of 6), vascular endoluminal invasion (score of 6), pleural nodule (score of 2), lobulated contour (score of 2), and heterogeneous internal density (score of 1). Area under the receiver operating characteristic curve was 0.76.

Conclusions:
TETs with clearly invasive or metastatic features seen on CT are associated with having higher AJCC/UICC pathologic TNM stage, as expected. However, features of lobulated contour and heterogeneous internal density are also associated with higher stage disease. These findings need to be validated in an independent cohort.
Muramyl Dipeptide Enhances Thermal Injury-Induced Autophagy and Inflammatory Cytokine Response of Lungs via Activation of NOD2/Rick Signaling Pathway in Rats
Authors: Wu Xiao-Jing , Liang Hui , Zhang Ying , Yang Xu-Ming , Wang Hong-Yu , Li Hui , Li Xin-Yi , Chen Kai , Wang Yan-Lin , Li Jian-Guo , Zhang Zong-Ze , Song Xue-Min 
Published: December 2017

ABSTRACT

Objective:
Nucleotide-binding oligomerization domain 2 (NOD2) is the innate receptor of muramyl dipeptide (MDP). Our previous study revealed that MDP could enhance thermal injury-induced inflammatory cytokine production and organ function injury in rats. The present study was to determine the effect of MDP on autophagy and NOD2/receptor-interacting serine/threonine protein kinases (RICK) signaling pathway of lung injury after thermal injury.

Methods:
Forty male Sprague–Dawlay rats were randomly divided into four groups: normal control (NC) group, MDP group, Scald group, and MDP + Scald group. Scald group only suffered 20% total body surface area third-degree (TBSA) thermal injury. MDP group was only administered 5.0 mg/kg MDP through the left femoral vein; 5.0 mg/kg MDP was administered through the left femoral vein at 24 h after thermal injury in the MDP + Scald group.

Results:
TBSA thermal injury (20%) not only significantly increased the plasma inflammatory cytokines production, but also elevated the expression of LC3-I/II, the accumulation of autophagosome in the lung tissue. Compared with the Scald group, MDP + Scald double hit led to more serious inflammatory responses and higher expression of NOD2 mRNA, RICK, NF-κB p65, LC3-I/II, and the accumulation of more autophagosome in the lung tissue.

Conclusions:
MDP enhances thermal injury-induced autophagy and proinflammatory cytokine response of lung injury, which could be achieved via activating the NOD2/RICK signaling pathway in rats.
The reproducibility of research and the misinterpretation of
p
-values
Authors: Colquhoun David 
Published: December 2017

We wish to answer this question: If you observe a ‘significant’
p
-value after doing a single unbiased experiment, what is the probability that your result is a false positive? The weak evidence provided by
p-
values between 0.01 and 0.05 is explored by exact calculations of false positive risks. When you observe
p
= 0.05, the odds in favour of there being a real effect (given by the likelihood ratio) are about 3 : 1. This is far weaker evidence than the odds of 19 to 1 that might, wrongly, be inferred from the
p-
value. And if you want to limit the false positive risk to 5%, you would have to assume that you were 87% sure that there was a real effect before the experiment was done. If you observe
p

=
0.001 in a well-powered experiment, it gives a likelihood ratio of almost 100 : 1 odds on there being a real effect. That would usually be regarded as conclusive. But the false positive risk would still be 8% if the prior probability of a real effect were only 0.1. And, in this case, if you wanted to achieve a false positive risk of 5% you would need to observe
p
= 0.00045. It is recommended that the terms ‘significant’ and ‘non-significant’ should never be used. Rather,
p-
values should be supplemented by specifying the prior probability that would be needed to produce a specified (e.g. 5%) false positive risk. It may also be helpful to specify the minimum false positive risk associated with the observed
p-
value. Despite decades of warnings, many areas of science still insist on labelling a result of
p
< 0.05 as ‘statistically significant’. This practice must contribute to the lack of reproducibility in some areas of science. This is before you get to the many other well-known problems, like multiple comparisons, lack of randomization and
p-
hacking. Precise inductive inference is impossible and replication is the only way to be sure. Science is endangered by statistical misunderstanding, and by senior people who impose perverse incentives on scientists.
SciRide Finder: a citation-based paradigm in biomedical literature search
Authors: Volanakis Adam , Konrad Krawczyk 
Published: December 2017

AbstractThere are more than 26 million peer-reviewed biomedical research items according to Medline/PubMed. This breadth of information is indicative of the progress in biomedical sciences on one hand, but an overload for scientists performing literature searches on the other. A major portion of scientific literature search is to find statements, numbers and protocols that can be cited to build an evidence-based narrative for a new manuscript. Because science builds on prior knowledge, such information has likely been written out and cited in an older manuscript. Thus, Cited Statements, pieces of text from scientific literature supported by citing other peer-reviewed publications, carry significant amount of condensed information on prior art. Based on this principle, we propose a literature search service, SciRide Finder (finder.sciride.org), which constrains the search corpus to such Cited Statements only. We demonstrate that Cited Statements can carry different information to this found in titles/abstracts and full text, giving access to alternative literature search results than traditional search engines. We further show how presenting search results as a list of Cited Statements allows researchers to easily find information to build an evidence-based narrative for their own manuscripts.
Sex differences in the genetic architecture of obsessive-compulsive disorder
Authors: Khramtsova Ekaterina A. , Heldman Raphael , Derks Eske M. , Yu Dongmei ,   TS/OCD Psychiatric Genomics Disorders Workgroup, Davis Lea K. , Stranger Barbara E. 
Published: December 2017

AbstractObsessive-compulsive disorder (OCD), a highly heritable complex phenotype, demonstrates sexual dimorphism in age of onset and clinical presentation, suggesting a possible sex difference in underlying genetic architecture. We present the first genome-wide characterization of the sex-specific genetic architecture of OCD, utilizing the largest set of OCD cases and controls available from the Psychiatric Genomics Consortium. We assessed evidence for several mechanisms that may contribute to sexual-dimorphism including a sexually dimorphic liability threshold, the presence of individual sex-specific risk variants on the autosomes and the X chromosome, genetic and phenotypic heterogeneity, and sex-specific pleiotropic effects. We observed a strong genetic correlation between male and female OCD and no evidence for a sexually dimorphic liability threshold model. While we did not detect any sex-specific genome-wide associations, we observed that the SNPs with sexually dimorphic effects showed an enrichment of regulatory variants influencing expression of genes in immune tissues. Furthermore, top sex-specific genome-wide associations were enriched for regulatory variants in different tissues, suggesting evidence for potential sex difference in the biology underlying risk for OCD. These findings suggest that future studies with larger sample sizes hold great promise for the identification of sex-specific risk factors for OCD, significantly advancing our understanding of the differences in the genetic basis of sexually dimorphic neuropsychiatric traits.
Serum proteins can successfully predict self-reported ethnicity: Implications for precision-medicine
Authors: Bishnoi Ram J , Palmer Raymond , Royall Donald R 
Published: December 2017

AbstractThe effects of inter-individual variability on disease treatment and prevention are important to the goals of “precision medicine” 1. In biomedical research, consideration of racial or ethnic differences allows generation and exploration of hypotheses about interactions among genetic and environmental factors responsible for differential medical outcomes. The US National Institutes of Health, therefore recommends adequate participation of subjects from ethnic minority groups in research studies. Nevertheless, considerable debate has focused on validity of race or ethnicity as biological construct 2. Inconsistent definition of race/ethnicity and insignificant genetic variations between ethnic groups have invited disregard to this construct 3. On the contrary, differences in prevalence, expression and outcomes of various diseases among ethnic groups argue for continued and focused attention to ethnicity as important predicting variable. In context of Alzheimer’s disease (AD), we have previously reported that ethnicity does moderates the proteomic markers of dementia 4. Here, we attempted to classify and predict selfreported ethnicity (Hispanic or non-Hispanic white, [NHW]) using a limited serum profile of 107 proteins. Random Forest (RF) classification method was able to discriminate those two ethnicities with 95% accuracy and could successfully predict ethnicity in an independent test-set (Area under ROC curve: 0.97). Variable selection method led to a condensed set of six proteins which yielded comparable classification and prediction accuracy. Our results provide preliminary evidence for proteomic variability between ethnic groups, and biological validity of ethnicity construct. Moreover, they also offer an opportunity to exploit these differences towards the objectives of precision medicine.
CREAM: Clustering of genomic REgions Analysis Method
Authors: Tonekaboni Seyed Ali Madani , Mazrooei Parisa , Kofia Victor , Haibe-Kains Benjamin , Lupien Mathieu 
Published: December 2017

ABSTRACTCellular identity relies on cell type-specific gene expression profiles controlled by cis-regulatory elements (CREs), such as promoters, enhancers and anchors of chromatin interactions. CREs are unevenly distributed across the genome, giving rise to distinct subsets such as individual CREs and Clusters Of cis-Regulatory Elements (COREs), also known as super-enhancers. Identifying COREs is a challenge due to technical and biological features that entail variability in the distribution of distances between CREs within a given dataset. To address this issue, we developed a new unsupervised machine learning approach termed Clustering of genomic REgions Analysis Method (CREAM) that outperforms the Ranking Of Super Enhancer (ROSE) approach. Specifically CREAM identified COREs are enriched in CREs strongly bound by master transcription factors according to ChIP-seq signal intensity, are proximal to highly expressed genes, are preferentially found near genes essential for cell growth and are more predictive of cell identity. Moreover, we show that CREAM enables subtyping primary prostate tumor samples according to their CORE distribution across the genome. We further show that COREs are enriched compared to individual CREs at TAD boundaries and these are preferentially bound by CTCF and factors of the cohesin complex (e.g.: RAD21 and SMC3). Finally, using CREAM against transcription factor ChIP-seq reveals CTCF and cohesin-specific COREs preferentially at TAD boundaries compared to intra-TADs. CREAM is available as an open source R package (https://CRAN.R-project.org/package=CREAM) to identify COREs from cis-regulatory annotation datasets from any biological samples.
The control of tonic pain by active relief learning
Authors: Zhang Suyi , Mano Hiroaki , Lee Michael , Yoshida Wako , Kawato Mitsuo , Robbins Trevor W , Seymour Ben 
Published: December 2017

AbstractTonic pain after injury characterises a behavioural state that prioritises recovery. Although generally suppressing cognition and attention, tonic pain needs to allow effective relief learning so that the cause of the pain can be reduced if possible. Here, we describe a central learning circuit that supports learning of relief and concurrently suppresses the level of ongoing pain. We used computational modelling of behavioural, physiological and neuroimaging data in two experiments in which subjects learned to terminate tonic pain in static and dynamic escape-learning paradigms. In both studies, we show that active relief-seeking involves a reinforcement learning process manifest by error signals observed in the dorsal putamen. Critically, this system also uses an uncertainty (‘associability’) signal detected in pregenual anterior cingulate cortex that both controls the relief learning rate, and endogenously and parametrically modulates the level of tonic pain. The results define a self-organising learning circuit that allows reduction of ongoing pain when learning about potential relief.
Rethinking phylogenetic comparative methods
Authors: Uyeda Josef C. , Zenil-Ferguson Rosana , Pennell Matthew W. 
Published: December 2017

AbstractAs a result of the process of descent with modification, closely related species tend to be similar to one another in a myriad different ways. In statistical terms, this means that traits measured on one species will not be independent of traits measured on others. Since their introduction in the 1980s, phylogenetic comparative methods (PCMs) have been framed as a solution to this problem. In this paper, we argue that this way of thinking about PCMs is deeply misleading. Not only has this sowed widespread confusion in the literature about what PCMs are doing but has led us to develop methods that are susceptible to the very thing we sought to build defenses against — unreplicated evolutionary events. Through three Case Studies, we demonstrate that the susceptibility to singular events is indeed a recurring problem in comparative biology that links several seemingly unrelated controversies. In each Case Study we propose a potential solution to the problem. While the details of our proposed solutions differ, they share a common theme: unifying hypothesis testing with data-driven approaches (which we term “phylogenetic natural history”) to disentangle the impact of singular evolutionary events from that of the factors we are investigating. More broadly, we argue that our field has, at times, been sloppy when weighing evidence in support of causal hypotheses. We suggest that one way to refine our inferences is to re-imagine phylogenies as probabilistic graphical models; adopting this way of thinking will help clarify precisely what we are testing and what evidence supports our claims.
A Basal Ganglia Circuit Sufficient To Guide Birdsong Learning
Authors: Xiao Lei , Chattree Gaurav , Garcia Oscos Francisco , Cao Mou , Wanat Matthew J. , Roberts Todd F. 
Published: December 2017

SUMMARYLearning complex vocal behaviors, like speech and birdsong, is thought to rely on continued performance evaluation. Whether candidate performance evaluation circuits in the brain are sufficient to guide vocal learning is not known. Here, we test the sufficiency of VTA projections to the vocal basal ganglia (Area X) in singing zebra finches, a songbird species that learns to produce a complex and stereotyped multi-syllabic courtship song during development. We optogenetically manipulate VTA axon terminals in singing birds contingent on how the pitch of individual song syllables are naturally performed. We find that optical excitation and inhibition of VTA terminals have opponent effects on future performances of targeted song syllables and are each sufficient to reliably guide learned changes in song, consistent with positive and negative reinforcement of performance outcomes. These findings define a central role for reinforcement mechanisms in learning vocalizations and provide the first demonstration of minimal circuit elements for learning vocal behaviors.