bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiparity improves outcomes after cerebral ischemia in female mice despite features of increased metabovascular risk
Authors: Ritzel Rodney M. , Patel Anita R. , Spychala Monica , Verma Rajkumar , Crapser Joshua , Koellhoffer Edward C. , Schrecengost Anna , Jellison Evan R. , Zhu Liang , Venna Venugopal Reddy , McCullough Louise D. 
Published: June 2017

Significance
Stroke is an age-related disease that disproportionately affects women. Although experimental studies have identified several hormonal and genetic factors underlying these differences, little is known about how reproductive experience influences risk. This study examined the role of pregnancy and parturition on neurovascular function and behavior in both normal female mice and in females exposed to stroke. We found that reproductive experience increases systemic metabolic risk and results in significant behavioral deficits that are associated with CNS immunosuppression. After stroke, however, multiparous females exhibited smaller infarct volumes, attenuated inflammatory responses, enhanced angiogenesis, and improved behavioral recovery. Although the precise mechanisms underlying this paradoxical finding remain unknown, parity was associated with higher VEGF and improved postischemic vascular remodeling.
Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1
Authors: Shydlovskyi Sergii , Zienert Anke Y. , Ince Semra , Dovengerds Christine , Hohendahl Annika , Dargazanli Julia M. , Blum Ailisa , Günther Saskia D. , Kladt Nikolay , Stürzl Michael , Schauss Astrid C. , Kutsch Miriam , Roux Aurélien , Praefcke Gerrit J. K. , Herrmann Christian 
Published: June 2017

Significance
In the human organism, guanylate-binding proteins (GBPs) are involved in antimicrobial and antiviral activity, but the mechanism of GBPs’ action remains poorly understood. We have discovered that binding of a substrate molecule, GTP, to the enzyme triggers the release of an aforemasked lipid anchor, which results in GBP polymerization on the one hand and in the attachment of GBPs to lipid membranes on the other. Thus, membrane binding of GBPs competes with protein polymerization and, furthermore, leads to the membrane tethering, which could play a role in a clearance of engulfed pathogens from the cell. Altogether, our findings give deeper insights into GBPs’ molecular mechanism in the course of pathogen response.
Cumulative Intracranial Tumor Volume Augments the Prognostic Value of Diagnosis-Specific Graded Prognostic Assessment Model for Survival in Patients with Melanoma Cerebral Metastases
Authors: Hirshman Brian R , Wilson Bayard R , Ali Mir Amaan , Schupper Alexander J , Proudfoot James A , Goetsch Steven J , Carter Bob S , Sinclair Georges , Bartek Jiri , Chiang Veronica , Fogarty Gerald , Hong Angela , Chen Clark C 
Published: June 2017

Abstract

BACKGROUND
The diagnosis-specific graded prognostic assessment scale (ds-GPA) for patients with melanoma brain metastasis (BM) utilizes only 2 key prognostic variables: Karnofsky performance status and the number of intracranial metastases. We wished to determine whether inclusion of cumulative intracranial tumor volume (CITV) into the ds-GPA model for melanoma augmented its prognostic value.

OBJECTIVE
To determine whether or not CITV augments the ds-GPA prognostic scale for melanoma.

METHODS
We analyzed the survival pattern of 344 melanoma patients with BM treated with stereotactic radiosurgery (SRS) at separate institutions and validated our findings in an independent cohort of 201 patients. The prognostic value of ds-GPA for melanoma was quantitatively compared with and without the addition of CITV using the net reclassification index (NRI > 0) and integrated discrimination improvement (IDI) metrics.

RESULTS
The incorporation of CITV into the melanoma-specific ds-GPA model enhanced its prognostic accuracy. Addition of CITV to the ds-GPA model significantly improved its prognostic value, with NRI > 0 of 0.366 (95% CI: 0.125-0.607, P = .002) and IDI of 0.024 (95% CI: 0.008-0.040, P = .004). We validated these findings that CITV improves the prognostic utility of melanoma ds-GPA in an independent cohort of 201 melanoma cohort.

CONCLUSION
The prognostic value of the ds-GPA scale for melanoma BM is enhanced by the incorporation of CITV.
A correlation analysis framework for localization-based super-resolution microscopy
Authors: Schnitzbauer Joerg , Wang Yina , Bakalar Matthew , Chen Baohui , Nuwal Tulip , Zhao Shijie , Huang Bo 
Published: June 2017

AbstractSuper-resolution images reconstructed from single-molecule localizations can reveal cellular structures close to the macromolecular scale and are now being used routinely in many biomedical research applications. However, because of their coordinate-based representation, a widely applicable and unified analysis platform that can extract a quantitative description and biophysical parameters from these images is yet to be established. Here, we propose a conceptual framework for correlation analysis of coordinate-based super-resolution images using distance histograms. We demonstrate the application of this concept in multiple scenarios including image alignment, tracking of diffusing molecules, as well as for quantification of colocalization.Significance statementCorrelation analysis is one of the most widely used image processing method. In the quantitative analysis of localization-based super-resolution images, there still lacks a generalized coordinate-based correlation analysis framework to take fully advantage of the super-resolution information. We show a coordinate-based correlation analysis framework for localization-based super-resolution microscopy. This framework is highly general and flexible in that it can be easily extended to model the effect of localization uncertainty, to the time domain and other distance definitions, enabling it to be adapted for a wide range of applications. Our work will greatly benefit the quantitative interpretation of super-resolution images and thus the biological application of super-resolution microscopy.
The decline of malaria in Vietnam, 1991-2014
Authors: Goldlust Sandra M , Thuan Phung Duc , Duy Hoang Giang Dang , Thang Ngo Duc , Thwaites Guy E , Farrar Jeremy , Thanh Ngo Viet , Nguyen Tran Dang , Grenfell Bryan T , Boni Maciej F , Hien Tran Tinh 
Published: June 2017

AbstractA central component of malaria control initiatives throughout the world is the use of artemisinin-based combination therapies (ACTs) for treatment of uncomplicatedP. falcipariummalaria. Despite the well-documented clinical efficacy of ACTs, the population-level effects of ACT case management on malaria transmission have not been studied thoroughly until recently. An ideal case study for the population-level effects of artemisinin use can be found in Vietnam, where a major increase of malaria cases in the 1980s was followed by the gradual adoption of artemisinin-based clinical case management. We assembled annual data from Vietnam’s National Institutes for Malariology, Parasitology, and Entomology showing the degree to which artemisinin therapies were adopted in different provinces, the effort placed on vector control, and the funding available to provincial malaria control programs, from 1991 to 2014. Data on urbanization were also collected for this period. We found that a 10% increase in the artemisinin proportion of treatments procured by a provincial control program corresponded to a 32.8% (95% CI: 27.7 – 37.5%) decline in estimated malaria cases; the association persisted and the effect size was nearly unchanged if confirmed cases or suspected cases were used. There was no consistent effect of vector control on malaria cases in Vietnam as a whole, nor was any effect found when the data were broken up regionally. The association between urbanization and malaria was generally negative and sometimes statistically significant. This was most pronounced in the central region of Vietnam, where a 10% increase in urbanization corresponded to a 43.3% (95% CI: 21.6 – 58.9%) decrease in suspected malaria incidence; this association was not statistically significant if confirmed cases or estimated cases were used. The decline of malaria in Vietnam from 1991 to 2014 can largely be attributed to the rapid adoption of artemisinin-based drugs. Recent analyses of aggregated data from Africa have shown that insecticide-treated nets have had the greatest effect on lowering malaria prevalence over the past fifteen years, suggesting that the success of different types of malaria interventions is region specific. Continuing global efforts on malaria elimination should focus on both vector control measures and increased access to artemisinin-combination therapies.
In silicoidentification of non-coding RNAs inHalobacterium salinarum NRC-1, a model archeon organism
Authors: Fonseca M. A. S. , Vêncio R. Z. N. 
Published: June 2017

AbstractBackgroundIn addition to the regulatory elements already known, for instance, transcription factors or post-translation modifications, there is growing interest in the regulatory role played by non-coding RNA molecules (ncRNA), whose functions are performed at a different level of biological information processing. Model organisms provide a convenient way of working in the laboratory, and different research groups use these models to conduct studies on the cellular mechanisms present in these organisms. Although some ncRNAs elements have been found in theHalobacterium salinarummodel organism, we believe that not enough is known about these genomic regions.MethodsTherefore, anin silicoanalysis for ncRNA identification was conducted onH. salinarumNRC-1. Considering a data integration perspective and some available methodologies, several machine learning models were built and used to designate candidate ncRNAs genome regions.ResultsA total of 42 new ncRNAs were identified. Combing analysis with other available tools, it had been observed that some suggested candidates also was found with different methodologies and thus, it highlights the proposed results.
Twelve Elements of Visualization and Analysis for Tertiary and Quaternary Structure of Biological Molecules
Authors: Youkharibache Philippe 
Published: June 2017

AbstractDuring the last decades, 3D Molecular Graphics in Life Sciences has been used almost exclusively by experts through complex software and applications ranging from Structural Biology to Computer Aided Drug Design. The emergence of JavaScript and WebGL as a viable platform has enabled 3D visualization of biomolecular structures through Web browsers, without any need for specialized software. Although still in its infancy, Web Molecular Graphics opens new perspectives. This white paper, proposes a set of Twelve Elements to consider to enable 3D visualization and structural analyses of biological systems in Web molecular viewers. The Elements go beyond 3D graphics and propose an integrated approach to visualize and analyze molecular entities and their interactions in multiple dimensions, at multiple levels of details, for diverse users. The bridging of 1D sequence browsers and 3D structure viewers, possible under a Web browser, enables information flow where molecular biologists can use structural information directly at the sequence level. Given the tsunami of sequence information linked to diseases from next generation sequencing - in need for interpretation - making structural information readily available to research scientists is a tremendous opportunity for medical discovery. The Twelve Elements are conceptual and are intended to entice developers to architect software components and APIs, and to gather together as a community around common goals and open source software. A few features of emerging viewers, all available as open source, are highlighted. Speed and quality of 3D graphics for large molecular systems, the interoperability of Web components, and the instantaneous sharing of annotated visualizations through the Web, are some of the most amazing and promising capabilities of 3D Web viewing, opening bright perspectives for Life Sciences research.
Structural brain development: a review of methodological approaches and best practices
Authors: Vijayakumar Nandita , Mills Kathryn L. , Alexander-Bloch Aaron , Tamnes Christian K. , Whittle Sarah 
Published: June 2017

AbstractContinued advances in neuroimaging technologies and statistical modelling capabilities have improved our knowledge of structural brain development in children and adolescents. While this has provided an increasingly nuanced understanding of brain development, the field is still plagued by inconsistent findings. This review highlights the methodological diversity in existing longitudinal magnetic resonance imaging (MRI) studies on structural brain development during childhood and adolescence, and addresses how such variation might contribute to inconsistencies in the literature. We discuss the impact of method choices at multiple decision points across the research process, from study design and sample selection, to image processing and statistical analysis. We also highlight the extent to which different methodological considerations have been empirically examined, drawing attention to specific areas that would benefit from future investigation. Where appropriate, we recommend certain best practices that would be beneficial for the field to adopt, including greater completeness and transparency in reporting methods, in order to ultimately develop an accurate and detailed understanding of normative child and adolescent brain development.
A National Estimate of the Health and Cost Burden ofEscherichia coliBacteraemia in the Hospital Setting: The Importance of Antibiotic Resistance
Authors: Naylor NR , Pouwels KB , Hope R , Green N , Henderson KL , Knight GM , Atun R , Robotham JV , Deeny SR 
Published: June 2017

AbstractBackgroundAntibiotic resistance poses a threat to public health and a burden to healthcare systems.Escherichia colicauses more bacteraemia cases in England than any other bacterial species, these infections, in part due to their high incidence, also pose a significant antibiotic resistance burden. The main aim of this study was to estimate the impact ofE. colibacteraemia on patient in-hospital mortality and length of stay. Secondarily, this study also aimed to estimate the effect of antibiotic resistance on these outcomes.Methods and FindingsCase patients were adultE. colibacteraemia patients infected between July 2011 and June 2012, as reported in an English national mandatory surveillance database, with susceptibility data taken from a national laboratory surveillance database. Control patients were all non-case, adult patients with an English hospital admission record. Case and control patient characteristics and admission information were taken from NHS Digital Datasets. ‘Resistance’ was defined as non-susceptible and intermediate isolates, whilst ‘susceptible’ was defined as susceptible and non-tested isolates. Time to in-hospital mortality and discharge was investigated through Cox proportional hazards models. To acquire estimates of excess length of stay, multistate models were constructed, with a unit bed day cost applied to estimate cost burden. The total number of case and control hospital spells was 14,051 and 8,919,275 respectively. Acquisition ofE. colibacteraemia was associated with a statistically significant increased daily risk of in-hospital mortality, especially for the first eight days of someone’s hospital admission [Hazard Ratio = 2.77 (95% confidence interval; 2.61-2.94)]. Antibiotic resistance did not seem to significantly increase this risk further, though did significantly reduce risk of experiencing a discharge event (dead or alive).E.colibacteraemia was estimated to cost £14,340,900 over the study period (rounded to the nearest £100), with resistance associated with excess costs per infection of £220 - £420 dependent on resistance type, for those where a significant impact was found (rounded to the nearest £10).ConclusionsE. colibacteraemia places a significant burden on patient health and on the hospital sector in England. Resistance is an important factor on length of stay with regards to such infections.
A genetic investigation of sex bias in the prevalence of attention deficit hyperactivity disorder
Authors: Martin Joanna , Walters Raymond K. , Demontis Ditte , Mattheisen Manuel , Lee S. Hong , Robinson Elise , Brikell Isabell , Ghirardi Laura , Larsson Henrik , Lichtenstein Paul , Eriksson Nicholas , Werge Thomas , Mortensen Preben Bo , Giørtz Pedersen Marianne , Mors Ole , Nordentoft Merete , Hougaard David M. , Bybjerg-Grauholm Jonas , Wray Naomi , Franke Barbara , Faraone Stephen V. , O’Donovan Michael C. , Thapar Anita , Børglum Anders D. , Neale Benjamin M. 
Published: June 2017

AbstractAttention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is 2-7 times more common in males than females. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. We analyzed genome-wide common variants from the Psychiatric Genomics Consortium and iPSYCH Project (20,183 cases, 35,191 controls) and Swedish population-registry data (N=77,905 cases, N=1,874,637 population controls). We find strong genetic correlation for ADHD across sex and no mean difference in polygenic burden across sex. In contrast, siblings of female probands are at an increased risk of ADHD, compared to siblings of male probands. The results also suggest that females with ADHD are at especially high risk of comorbid developmental conditions. Overall, this study supports a greater familial burden of risk in females with ADHD and some clinical and etiological heterogeneity. However, autosomal common variants largely do not explain the sex bias in ADHD prevalence.
Genetic context and proliferation determine contrasting patterns of copy number amplification and loss for 5S and 45S ribosomal DNA arrays in cancer
Authors: Wang Meng , Lemos Bernardo 
Published: June 2017

AbstractThe multicopy 45S ribosomal DNA (45S rDNA) array gives origin to the nucleolus, the first discovered nuclear organelle, site of Poll I 45S rRNA transcription and key regulator of cellular metabolism, DNA repair response, genome stability, and global epigenetic states. The multicopy 5S ribosomal DNA array (5S rDNA) is located on a separate chromosome, encodes the 5S rRNA transcribed by Pol III, and exhibits concerted copy number variation (cCNV) with the 45S rDNA array in human blood. Here we combined genomic data from >700 tumors and normal tissues to provide a portrait of ribosomal DNA variation in human tissues and cancers of diverse mutational signatures. We show that most cancers undergo coupled 5S rDNA array amplification and 45S rDNA loss, with abundant inter-individual variation in rDNA copy number of both arrays, and concerted modulation of 5S-45S copy number in some but not all tissues. Analysis of genetic context revealed associations between the presence of specific somatic alterations, such as P53 mutations in stomach and lung adenocarcinomas, and coupled 5S gain / 45S loss. Finally, we show that increased proliferation rates along cancer lineages can partially explain contrasting copy number changes in the 5S and 45S rDNA arrays. We suggest that 5S rDNA amplification facilitates increased ribosomal synthesis in cancer, whereas 45S rDNA loss emerges as a byproduct of transcription-replication conflict in highly proliferating tumor cells. Our results highlight the tissue- specificity of concerted copy number variation and uncover contrasting changes in 5S and 45S rDNA copy number along rapidly proliferating cell lineages.Lay SummaryThe 45S and 5S ribosomal DNA (rDNA) arrays contain hundreds of rDNA copies, with substantial variability across individuals and species. Although physically unlinked, both arrays exhibit concerted copy number variation. However, whether concerted copy number is universally observed across all tissues is unknown. It also remains unknown if rDNA copy number may vary in tissues and cancer lineages. Here we showed that most cancers undergo coupled 5S rDNA array amplification and 45S rDNA loss, and concerted 5S-45S copy number variation in some but not all tissues. The coupled 5S amplification and 45S loss is associated with the presence of certain somatic genetic variations, as well as increased cancerous cell proliferation rate. Our research highlights the tissue- specificity of concerted copy number variation and uncover contrasting changes in rDNA copy number along rapidly proliferating cell lineages. Our observations raise the prospects of using 5S and 45S ribosomal DNA states as indicators of cancer status and targets in new strategies for cancer therapy.
Functional selectivity for face processing in the temporal voice area of early deaf individuals
Authors: Benetti Stefania , van Ackeren Markus J. , Rabini Giuseppe , Zonca Joshua , Foa Valentina , Baruffaldi Francesca , Rezk Mohamed , Pavani Francesco , Rossion Bruno , Collignon Olivier 
Published: June 2017

AbstractBrain systems supporting face and voice processing both contribute to the extraction of important information for social interaction (e.g., person identity). How does the brain reorganize when one of these channels is absent? Here we explore this question by combining behavioral and multimodal neuroimaging measures (magneto-encephalography and functional imaging) in a group of early deaf humans. We show enhanced selective neural response for faces and for individual face coding in a specific region of the auditory cortex that is typically specialized for voice perception in hearing individuals. In this region, selectivity to face signals emerges early in the visual processing hierarchy, shortly following typical face-selective responses in the ventral visual pathway. Functional and effective connectivity analyses suggest reorganization in long-range connections from early visual areas to the face-selective temporal area in individuals with early and profound deafness. Altogether, these observations demonstrate that regions that typically specialize for voice processing in the hearing brain preferentially reorganize for face processing in born deaf people. Our results support the idea that cross-modal plasticity in case of early sensory deprivation relates to the original functional specialization of the reorganized brain regions.