bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two-Tier Mapper, an unbiased topology-based clustering method for enhanced global gene expression analysis
Authors: Jeitziner Rachel , Carrière Mathieu , Rougemont Jacques , Oudot Steve , Hess Kathryn , Brisken Cathrin 
Published: February 2019

Abstract

Motivation
Unbiased clustering methods are needed to analyze growing numbers of complex datasets. Currently available clustering methods often depend on parameters that are set by the user, they lack stability, and are not applicable to small datasets. To overcome these shortcomings we used topological data analysis, an emerging field of mathematics that discerns additional feature and discovers hidden insights on datasets and has a wide application range.

Results
We have developed a topology-based clustering method called Two-Tier Mapper (TTMap) for enhanced analysis of global gene expression datasets. First, TTMap discerns divergent features in the control group, adjusts for them, and identifies outliers. Second, the deviation of each test sample from the control group in a high-dimensional space is computed, and the test samples are clustered using a new Mapper-based topological algorithm at two levels: a global tier and local tiers. All parameters are either carefully chosen or data-driven, avoiding any user-induced bias. The method is stable, different datasets can be combined for analysis, and significant subgroups can be identified. It outperforms current clustering methods in sensitivity and stability on synthetic and biological datasets, in particular when sample sizes are small; outcome is not affected by removal of control samples, by choice of normalization, or by subselection of data. TTMap is readily applicable to complex, highly variable biological samples and holds promise for personalized medicine.

Availability and implementation
TTMap is supplied as an R package in Bioconductor.

Supplementary information
Supplementary data are available at Bioinformatics online.
Variational infinite heterogeneous mixture model for semi-supervised clustering of heart enhancers
Authors: Mehdi Tahmid F , Singh Gurdeep , Mitchell Jennifer A , Moses Alan M 
Published: February 2019

Abstract

Motivation
Mammalian genomes can contain thousands of enhancers but only a subset are actively driving gene expression in a given cellular context. Integrated genomic datasets can be harnessed to predict active enhancers. One challenge in integration of large genomic datasets is the increasing heterogeneity: continuous, binary and discrete features may all be relevant. Coupled with the typically small numbers of training examples, semi-supervised approaches for heterogeneous data are needed; however, current enhancer prediction methods are not designed to handle heterogeneous data in the semi-supervised paradigm.

Results
We implemented a Dirichlet Process Heterogeneous Mixture model that infers Gaussian, Bernoulli and Poisson distributions over features. We derived a novel variational inference algorithm to handle semi-supervised learning tasks where certain observations are forced to cluster together. We applied this model to enhancer candidates in mouse heart tissues based on heterogeneous features. We constrained a small number of known active enhancers to appear in the same cluster, and 47 additional regions clustered with them. Many of these are located near heart-specific genes. The model also predicted 1176 active promoters, suggesting that it can discover new enhancers and promoters.

Availability and implementation
We created the ‘dphmix’ Python package: https://pypi.org/project/dphmix/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Circulating inflammation markers and colorectal adenoma risk
Authors: Huang Wen-Yi , Berndt Sonja I , Shiels Meredith S , Katki Hormuzd A , Chaturvedi Anil K , Wentzensen Nicolas , Trabert Britton , Kemp Troy J , Pinto Ligia A , Hildesheim Allan , Rothman Nathaniel , Purdue Mark P 
Published: February 2019

AbstractInflammation is a driver of colorectal neoplasia; however, what particular inflammatory processes play a role in early carcinogenesis are unclear. We compared serum levels of 78 inflammation markers between 171 pathologically confirmed colorectal adenoma cases (including 48 incident cases) and 344 controls within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used weighted multivariable logistic regression to compute odds ratio (OR) and 95% confidence interval (CI). We found 14 markers associated with risk of adenoma overall; three of these were also associated with incident adenoma: CC-chemokine cysteine motif chemokine ligand 20 (CCL20) [overall adenoma fourth versus first quartile: OR 4.8, 95% CI 2.0–12, Ptrend 0.0007; incident adenoma third versus first tertile: OR 4.6, 95% CI 1.0–22, Ptrend 0.03], growth-related gene oncogene products (GRO) [OR 3.8, 95% CI 1.6–9.3, Ptrend 0.006 and OR 3.6, 95% CI 1.1–12, Ptrend 0.04, respectively] and insulin [OR 2.9, 95% CI 0.8–10, Ptrend 0.05 and OR 7.8, 95% CI 1.3–46, Ptrend 0.03, respectively]. All statistical tests were two-sided. These results provide important new evidence implicating CCL20- and GRO-related pathways in early colorectal carcinogenesis and further support a role for insulin.
Long-term outcome in a case series of Denys–Drash syndrome
Authors: Roca Neus , Muñoz Marina , Cruz Alejandro , Vilalta Ramon , Lara Enrique , Ariceta Gema 
Published: February 2019

Abstract

Background
Denys–Drash syndrome (DDS) is a rare disease caused by mutations in exons 8 and 9 of the WT1 gene. It is characterized by the association of early onset steroid-resistant nephrotic syndrome (SRNS), Wilms’ tumour and, in some patients, intersex disorders, with increasing risk of gonadoblastoma. There are few published data concerning the long-term outcome of patients with DDS. The aim of this study was to report our experience.

Methods
Data were collected from five children (three boys) with confirmed DDS diagnosed from 1996 to 2017. The mean follow-up of these patients was 16 years.

Results
The patients presented with SRNS and diffuse mesangial sclerosis at renal biopsy. All patients were hypertensive and progressed to end-stage kidney disease, initiating dialysis at a mean age of 28 months. Three patients developed Wilms’ tumour 9 months after the SRNS was identified, which was treated by nephrectomy and chemotherapy. All five patients received kidney transplantation. SRNS did not recur after transplantation in any of the patients and graft survival was similar to that of other kidney transplant recipients in our programme. All three boys had ambiguous genitalia and cryptorchidism but a confirmed male karyotype (46, XY). One girl presented with gonadal agenesis, whereas the other one had normal female ovarian tissue and external genitalia. Both girls had a female karyotype (46, XX). Gonadoblastoma was not observed at any case.

Conclusions
Early DDS recognition in patients with SRNS is crucial due to its low prevalence, the specific treatment approach required and early detection of Wilms’ tumour. Few data are available regarding long-term outcomes.
Personalized medicine in cardio-oncology: the role of induced pluripotent stem cell
Authors: Sayed Nazish , Ameen Mohamed , Wu Joseph C 
Published: February 2019

Abstract
Treatment of cancer has evolved in the last decade with the introduction of new therapies. Despite these successes, the lingering cardiotoxic side-effects from chemotherapy remain a major cause of morbidity and mortality in cancer survivors. These effects can develop acutely during treatment, or even years later. Although many risk factors can be identified prior to beginning therapy, unexpected toxicity still occurs, often with lasting consequences. Specifically, cardiotoxicity results in cardiac cell death, eventually leading to cardiomyopathy and heart failure. Certain risk factors may predispose an individual to experiencing adverse cardiovascular effects, and when unexpected cardiotoxicity occurs, it is generally managed with supportive care. Animal models of chemotherapy-induced cardiotoxicity have provided some mechanistic insights, but the precise mechanisms by which these drugs affect the heart remains unknown. Moreover, the genetic rationale as to why some patients are more susceptible to developing cardiotoxicity has yet to be determined. Many genome-wide association studies have identified genomic variants that could be associated with chemotherapy-induced cardiotoxicity, but the lack of validation has made these studies more speculative rather than definitive. With the advent of human induced pluripotent stem cell (iPSC) technology, researchers not only have the opportunity to model human diseases, but also to screen drugs for their efficacy and toxicity using human cell models. Furthermore, it allows us to conduct validation studies to confirm the role of genomic variants in human diseases. In this review, we discuss the role of iPSCs in modelling chemotherapy-induced cardiotoxicity.
Predator-induced changes of male and female mating preferences: innate and learned components
Authors: Plath Martin , Liu Kai , Umutoni Diane , Gomes-Silva Guilherme , Wei Jie-Fei , Cyubahiro Eric , Chen Bo-Jian , Sommer-Trembo Carolin 
Published: February 2019

AbstractWhile many mating preferences have a genetic basis, the question remains as to whether and how learning/experience can modify individual mate choice decisions. We used wild-caught (predator-experienced) and F1 laboratory-reared (predator-naïve) invasive Western mosquitofish Gambusia affinis from China to test whether mating preferences (assessed in a first mate choice test) would change under immediate predation threat. The same individuals were tested in a second mate choice test during which 1 of 3 types of animated predators was presented: 1) a co-occurring predator, 2) a co-evolved but not currently co-occurring predator, and 3) a non-piscivorous species as control. We compared preference scores derived from both mate choice tests to separate innate from experiential effects of predation. We also asked whether predator-induced changes in mating preferences would differ between sexes or depend on the choosing individual’s personality type and/or body size. Wild-caught fish altered their mate choice decisions most when exposed to the co-occurring predator whereas laboratory-reared individuals responded most to the co-evolved predator, suggesting that both innate mechanisms and learning effects are involved. This behavior likely reduces individuals’ risk of falling victim to predation by temporarily moving away from high-quality (i.e., conspicuous) mating partners. Accordingly, effects were stronger in bolder than shyer, large- compared with small-bodied, and female compared with male focal individuals, likely because those phenotypes face an increased predation risk overall. Our study adds to the growing body of literature appreciating the complexity of the mate choice process, where an array of intrinsic and extrinsic factors interacts during decision-making.
Seascape context modifies how fish respond to restored oyster reef structures
Authors: Gilby Ben L , Olds Andrew D , Henderson Christopher J , Ortodossi Nicholas L , Connolly Rod M , Schlacher Thomas A 
Published: February 2019

Abstract
The seascape context of coastal ecosystems plays a pivotal role in shaping patterns in fish recruitment, abundance, and diversity. It might also be a principal determinant in structuring the recruitment of fish assemblages to restored habitats, but the trajectories of these relationships require further testing. In this study, we surveyed fish assemblages from 14 restored oyster reefs and 14 control sites in the Noosa River, Queensland, Australia, that differed in the presence or absence of seagrass within 500 m, over four periods using baited cameras. Fish assemblages at oyster reefs differed from those at control sites, with higher species richness (1.4 times) and more individuals of taxa that are harvested by fishers (1.8 times). The presence or absence of seagrass nearby affected the abundance of a key harvestable fish species (yellowfin bream Acanthopagrus australis) on oyster reefs, but not the overall composition of fish assemblages, species richness, or the total abundance of harvestable fishes overall. These findings highlight the importance of considering species-specific patterns in seascape utilization when selecting restoration sites and setting restoration goals, and suggest that the effects of restoration on fish assemblages might be optimized by focusing efforts in prime positions in coastal seascapes.
Expanding School Resources and Increasing Time on Task: Effects on Students’ Academic and Noncognitive Outcomes
Authors: Lavy Victor 
Published: February 2019

Abstract
This paper uses a natural experiment in Israel to assess the impact of school teaching resources and how it is used, “time-on-task”, on academic achievements and noncognitive outcomes. It exploits variation induced by a change in the funding formula that reduced instructional resources funding for some schools and increased them for others. The results suggest that increased school resources and students’ spending more time at school and on key tasks all lead to increased academic achievements with no behavioral costs. Separate estimations of the effect of increasing subject-specific instructional time per week also show positive and significant effects on math, science, and English test scores and small and nonsignificant effects on Hebrew test scores. However, there are no cross effects of additional instructional time across subjects. This evidence is robust to using different identification strategies. The evidence also shows that a longer school week increases the time that students spend on homework without reducing social and school satisfaction and without increasing school violence.
Long-Term Risk of Hospitalization Among Five-Year Survivors of Childhood Leukemia in the Nordic Countries
Authors: Sørensen Gitte Vrelits , Winther Jeanette Falck , de Fine Licht Sofie , Andersen Klaus Kaa , Holmqvist Anna Sällfors , Madanat-Harjuoja Laura , Tryggvadottir Laufey , Bautz Andrea , Lash Timothy L , Hasle Henrik 
Published: February 2019

AbstractBackgroundAdverse effects from childhood leukemia treatment may persist or present years after cure from cancer. We provide a comprehensive evaluation of subsequent hospitalization in five-year survivors of childhood acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML).MethodsIn the Adult Life after Childhood Cancer in Scandinavia Study, we identified 4003 five-year survivors diagnosed with childhood leukemia 1970–2008 in Denmark, Sweden, Iceland, and Finland. Survivors and 129 828 population comparisons were followed for first-time nonpsychiatric hospitalizations for 120 disease categories in the hospital registries. Standardized hospitalization rate ratios and absolute excess rates were calculated. All statistical tests were two-sided.ResultsSurvivors of ALL (n = 3391), AML (n = 389), and CML (n = 92) had an increased overall hospitalization rate compared with population comparisons. The rate ratio for any hospitalization was 1.95 (95% confidence interval [CI] = 1.83 to 2.07) in ALL, 3.09 (95% CI = 2.53 to 3.65) in AML, and 4.51 (95% CI = 3.03 to 6.00) in CML survivors and remained increased even 20 years from leukemia diagnosis. Corresponding absolute excess rates per 1000 person-years were 28.48 (95% CI = 24.96 to 32.00), 62.75 (95% CI = 46.00 to 79.50), and 105.31 (95% CI = 60.90 to 149.72).ConclusionLeukemia survivors have an increased rate of hospitalization for medical conditions. We provide novel insight into the relative and absolute rate of hospitalization for 120 disease categories in survivors of ALL, AML, and CML, which are likely to be informative for both survivors and healthcare providers.
Cognitive outcomes in meningioma patients undergoing surgery: individual changes over time and predictors of late cognitive functioning
Authors: Rijnen Sophie J M , Meskal Ikram , Bakker Marjan , De Baene Wouter , Rutten Geert-Jan M , Gehring Karin , Sitskoorn Margriet M 
Published: February 2019

Abstract

Background
Meningioma patients are known to face cognitive deficits before and after surgery. We examined individual changes in cognitive performance over time and identified preoperative predictors of cognitive functioning 12 months after surgery in a large sample of meningioma patients.

Methods
Patients underwent neuropsychological assessment (NPA) using CNS Vital Signs 1 day before (T0) and 3 (T3) and 12 (T12) months after surgery. Patients’ sociodemographically corrected scores on 7 cognitive domains were compared with performance of a normative sample using one-sample z tests and chi-square tests of independence. Reliable change indices with correction for practice effects were calculated for individual patients. Linear mixed effects models were used to identify preoperative predictors of performance at T12.

Results
At T0, 261 patients were assessed, and 229 and 82 patients were retested at T3 and T12, respectively. Patients showed impaired cognitive performance before and after surgery, and although performance improved on the group level, cognitive scores remained significantly lower than in the normative sample up to T12. On the individual level, performance remained stable in the majority of patients. Better preoperative performance, younger age, male sex, and higher educational level predicted better late cognitive performance.

Conclusions
Meningioma patients face serious and persistent pre- and postsurgical cognitive deficits. A preoperative NPA together with sociodemographic characteristics may provide valuable information on the late cognitive outcome of individual meningioma patients. These results can help to inform patients and clinicians on late cognitive outcomes at an early stage, and emphasizes the importance of presurgical NPA and timely cognitive rehabilitation.
The Cytokine Response Profile of Ebola Virus Disease in a Large Cohort of Rhesus Macaques Treated With Monoclonal Antibodies
Authors: Banadyga Logan , Siragam Vinayakumar , Zhu Wenjun , He Shihua , Cheng Keding , Qiu Xiangguo 
Published: February 2019

Abstract
Ebola virus (EBOV) is a highly pathogenic filovirus that causes outbreaks of a severe hemorrhagic fever known as EBOV disease (EVD). Ebola virus disease is characterized in part by a dysregulated immune response and massive production of both pro- and anti-inflammatory cytokines. To better understand the immune response elicited by EVD in the context of treatment with experimental anti-EBOV antibody cocktails, we analyzed 29 cytokines in 42 EBOV-infected rhesus macaques. In comparison to the surviving treated animals, which exhibited minimal aberrations in only a few cytokine levels, nonsurviving animals exhibited a dramatically upregulated inflammatory response that was delayed by antibody treatment.
The Contra Proferentem Rule: Contract Law’s Great Survivor
Authors: McCunn Joanna 
Published: February 2019

Abstract
The contra proferentem rule has been under sustained attack in recent years, as judges doubt whether it has any role to play in modern commercial contract law. This article sheds light on the function of the rule by examining its historical development. The rule has been part of English contract law for over 600 years, playing very different roles at each stage of its development. Lawyers since the medieval period have criticised the rule, but have succeeded in continually repurposing it to fit with new conceptions of contract law and to address the most pressing concerns of their day. This article shows that the contra proferentem rule can provide a fascinating case study in the development of common law doctrine, and argues that the future need not be wholly bleak for one of our longest-lived canons of construction.
Subfrontal Infrachiasmatic Approach to a Craniopharyngioma Resection: 2-Dimensional Operative Video
Authors: Aldave Guillermo , Zinn Pascal , Whitehead William E 
Published: February 2019

Abstract
Craniopharyngioma constitutes one of the most challenging tumors. The surgery may be the definitive treatment and multiple approaches have been described based on different anatomical considerations. The choice of the right approach is the key to optimize the resection and minimize the risks. Besides, the presentation of this tumor in the pediatric population can carry additional challenges that are not present in adults, like the absence of pneumatization of the sphenoid bone for an endoscopic endonasal approach. In this video, we present a case of a 6-yr-old girl with a large sellar-suprasellar craniopharyngioma. The fact that the sphenoid was not pneumatized and the chiasm was elevated 1.2 cm from the planum sphenoidal were some of the reasons to choose a subfrontal infrachiasmatic approach as we discuss and we show in the video. This approach has not been very well established in the literature but we demonstrate it can become a good alternative for a particular type of sellar-suprasellar tumors. Appropriate video authorization consent was obtained from the parent of the patient.
The Impact of Consumer Credit Access on Unemployment
Authors: Herkenhoff Kyle F 
Published: February 2019

AbstractUnemployed households’ access to unsecured revolving credit more than tripled over the last three decades. This article analyses how both cyclical fluctuations and trend increases in credit access impact the business cycle. The main quantitative result is that credit expansions and contractions have contributed to moderately deeper and more protracted recessions over the last 40 years. As more individuals obtained credit from 1977 to 2010, cyclical credit fluctuations affected a larger share of the population and became more important determinants of employment dynamics. Even though business cycles are more volatile, newborns strictly prefer to live in the economy with growing, but fluctuating, access to credit markets.
Increased and Decreased Superficial White Matter Structural Connectivity in Schizophrenia and Bipolar Disorder
Authors: Ji Ellen , Guevara Pamela , Guevara Miguel , Grigis Antoine , Labra Nicole , Sarrazin Samuel , Hamdani Nora , Bellivier Frank , Delavest Marine , Leboyer Marion , Tamouza Ryad , Poupon Cyril , Mangin Jean-François , Houenou Josselin 
Published: February 2019

AbstractSchizophrenia (SZ) and bipolar disorder (BD) are often conceptualized as “disconnection syndromes,” with substantial evidence of abnormalities in deep white matter tracts, forming the substrates of long-range connectivity, seen in both disorders. However, the study of superficial white matter (SWM) U-shaped short-range tracts remained challenging until recently, although findings from postmortem studies suggest they are likely integral components of SZ and BD neuropathology. This diffusion weighted imaging (DWI) study aimed to investigate SWM microstructure in vivo in both SZ and BD for the first time. We performed whole brain tractography in 31 people with SZ, 32 people with BD and 54 controls using BrainVISA and Connectomist 2.0. Segmentation and labeling of SWM tracts were performed using a novel, comprehensive U-fiber atlas. Analysis of covariances yielded significant generalized fractional anisotropy (gFA) differences for 17 SWM bundles in frontal, parietal, and temporal cortices. Post hoc analyses showed gFA reductions in both patient groups as compared with controls in bundles connecting regions involved in language processing, mood regulation, working memory, and motor function (pars opercularis, insula, anterior cingulate, precentral gyrus). We also found increased gFA in SZ patients in areas overlapping the default mode network (inferior parietal, middle temporal, precuneus), supporting functional hyperconnectivity of this network evidenced in SZ. We thus illustrate that short U-fibers are vulnerable to the pathological processes in major psychiatric illnesses, encouraging improved understanding of their anatomy and function.