bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ratcheting ambition to limit warming to 1.5 °C – trade-offs between emission reductions and carbon dioxide removal
Authors: Holz Ceecee , Siegel Lori S , Johnston Eleanor , Jones Andrew P , Sterman John 
Published: April 2018

Abstract
Mitigation scenarios to limit global warming to 1.5 °C or less in 2100 often rely on large amounts of carbon dioxide removal (CDR), which carry significant potential social, environmental, political and economic risks. A precautionary approach to scenario creation is therefore indicated. This letter presents the results of such a precautionary modelling exercise in which the models C-ROADS and En-ROADS were used to generate a series of 1.5 °C mitigation scenarios that apply increasingly stringent constraints on the scale and type of CDR available. This allows us to explore the trade-offs between near-term stringency of emission reductions and assumptions about future availability of CDR. In particular, we find that regardless of CDR assumptions, near-term ambition increase (‘ratcheting’) is required for any 1.5 °C pathway, making this letter timely for the facilitative, or Talanoa, dialogue to be conducted by the UNFCCC in 2018. By highlighting the difference between net and gross reduction rates, often obscured in scenarios, we find that mid-term gross CO2 emission reduction rates in scenarios with CDR constraints increase to levels without historical precedence. This in turn highlights, in addition to the need to substantially increase CO2 reduction rates, the need to improve emission reductions for non-CO2 greenhouse gases. Further, scenarios in which all or part of the CDR is implemented as non-permanent storage exhibit storage loss emissions, which partly offset CDR, highlighting the importance of differentiating between net and gross CDR in scenarios. We find in some scenarios storage loss trending to similar values as gross CDR, indicating that gross CDR would have to be maintained simply to offset the storage losses of CO2 sequestered earlier, without any additional net climate benefit.
GapRepairer: a server to model a structural gap and validate it using topological analysis
Authors: Jarmolinska Aleksandra I , Kadlof Michal , Dabrowski-Tumanski Pawel , Sulkowska Joanna I 
Published: April 2018

Abstract

Motivation
Over 25% of protein structures possess unresolved fragments. On the other hand, approximately 6% of protein chains have non-trivial topology (and form knots, slipknots, lassos and links). As the topology is fundamental for the proper function of proteins, modeling of topologically correct structures is decisive in various fields, including biophysics, biotechnology and molecular biology. However, none of the currently existing tools take into account the topology of the model and those which could be modified to include topology, demand experience in bioinformatics, protein topology and knot theory.

Results
In this work, we present the GapRepairer—the server that fills the gap in the spectrum of structure modeling methods. Its easy and intuitive interface offers the power of Modeller homology modeling to many non-experts in the field. This server determines the topology of templates and predicted structures. Such information when possible is used by the server to suggest the best model, or it can be used by the user to score models or to design artificially (dis)entangled structures.

Availability and implementation
GapRepairer server along with tutorials, usage notes, movies and the database of already repaired structures is available at http://gaprepairer.cent.uw.edu.pl.

Supplementary information
Supplementary data are available at Bioinformatics online.
Universal evolutionary selection for high dimensional silent patterns of information hidden in the redundancy of viral genetic code
Authors: Goz Eli , Zafrir Zohar , Tuller Tamir 
Published: April 2018

Abstract

Motivation
Understanding how viruses co-evolve with their hosts and adapt various genomic level strategies in order to ensure their fitness may have essential implications in unveiling the secrets of viral evolution, and in developing new vaccines and therapeutic approaches. Here, based on a novel genomic analysis of 2625 different viruses and 439 corresponding host organisms, we provide evidence of universal evolutionary selection for high dimensional ‘silent’ patterns of information hidden in the redundancy of viral genetic code.

Results
Our model suggests that long substrings of nucleotides in the coding regions of viruses from all classes, often also repeat in the corresponding viral hosts from all domains of life. Selection for these substrings cannot be explained only by such phenomena as codon usage bias, horizontal gene transfer and the encoded proteins. Genes encoding structural proteins responsible for building the core of the viral particles were found to include more host-repeating substrings, and these substrings tend to appear in the middle parts of the viral coding regions. In addition, in human viruses these substrings tend to be enriched with motives related to transcription factors and RNA binding proteins. The host-repeating substrings are possibly related to the evolutionary pressure on the viruses to effectively interact with host's intracellular factors and to efficiently escape from the host's immune system.

Supplementary information
Supplementary data are available at Bioinformatics online.
hts-nim: scripting high-performance genomic analyses
Authors: Pedersen Brent S , Quinlan Aaron R 
Published: April 2018

Abstract

Motivation
Extracting biological insight from genomic data inevitably requires custom software. In many cases, this is accomplished with scripting languages, owing to their accessibility and brevity. Unfortunately, the ease of scripting languages typically comes at a substantial performance cost that is especially acute with the scale of modern genomics datasets.

Results
We present hts-nim, a high-performance library written in the Nim programming language that provides a simple, scripting-like syntax without sacrificing performance.

Availability and implementation
hts-nim is available at https://github.com/brentp/hts-nim and the example tools are at https://github.com/brentp/hts-nim-tools both under the MIT license.
A Conceptual History of Recognition in British International Legal Thought
Authors: Clark Martin 
Published: April 2018

Abstract
This article examines the development of the concept of recognition in the writings of British jurists. It first outlines methodologies of conceptual history as applied to international legal concepts, before examining four strands of development of the concept of recognition from the mid-nineteenth to mid-twentieth centuries. It shows how the concept of recognition moved from examining intra-European diplomatic disagreements, to a focus on Christianity, civilisation and progress that barred non-European communities, to a late colonial-era emphasis on technicalities of government and territory, and eventually a state-centric account that normalised inferiority into difference, before emerging in the interwar period as a ‘basic concept’ of international law: intensely debated and closely tied to a range of political projects. The article concludes with reflections on why British thinking turns away from recognition in the 1950s, as the decolonising world turns to a new international law and self-determination.
Biodegradable coronary scaffolds: their future and clinical and technological challenges
Authors: Hytönen Jarkko P , Taavitsainen Jouni , Tarvainen Santeri , Ylä-Herttuala Seppo 
Published: April 2018

Abstract
Angioplasty and stenting are standard treatment options for both stabile occlusive coronary artery disease and acute myocardial infarctions. Over the last years, several biodegradable stent systems have entered pre-clinical and clinical evaluation and into clinical practice. A strong supporting scaffold is necessary after angioplasty to prevent elastic recoil of the vessel but in the long term a permanent metallic stent will only impair normal physiology of the artery wall. Thus, the main advantage of a resorbable system is the potential for better vessel recovery and function in the long term. The new stent systems differ from traditional stents in size and biological responses and questions have risen regarding their mechanical strength and increased risk of stent thrombosis. Here, we present current treatment options with biodegradable scaffolds, discuss further key areas for improvements and review novel technological advances in the context of all up-to-date clinical trial information. New material choices are also covered as well as special considerations for pre-clinical testing.
Scandal and Narrative in the
Heptaméron
Authors: Butterworth Emily 
Published: April 2018

Abstract

This article explores the relationships between scandal and narrative in Marguerite de Navarre’s
Heptaméron
. Scandal was a controversial and shifting keyword in the sixteenth century: the medieval secular connotations of socially reprehensible behaviour and outrage were still current, while Protestant discussions revived its biblical sense of the stumbling block in an individual’s path to salvation. The
Heptaméron
contains both kinds of scandal. Its stories are socially scandalous in their plots of adultery, treachery, and hypocrisy, but the storytellers also probe the theological idea that such behaviour could be a spiritual snare or stumbling block, especially in relation to what is presented frequently as the false teaching of the Franciscans. This article traces the dynamics of scandal in the
nouvelles
and between the storytellers, and argues that stories about scandalous behaviour might themselves constitute a scandal to the unwary reader. The
Heptaméron
acknowledges this possibility, exploring both the narrative of scandal and the scandal of narrative and emphasizing the contagious power of both.
Symmetries of Projective Spaces and Spheres
Authors: Gehér György Pál 
Published: April 2018

AbstractLet H be either a complex inner product space of dimension at least two or a real inner product space of dimension at least three, and let us fix an $\alpha \in (0,\tfrac{\pi }{2} )$. The purpose of this paper is to characterise all bijective transformations on the projective space P(H) which preserve the quantum angle $\alpha$ (or Fubini–Study distance $\alpha$) between lines in both directions. (Let us emphasise that we do not assume anything about the preservation of other quantum angles). For real inner product spaces and when $H=\mathbb{C}^2$ we do this for every $\alpha$, and when H is a complex inner product space of dimension at least three we describe the structure of such transformations for $\alpha \leq \tfrac{\pi }{4}$. Our result immediately gives an Uhlhorn-type generalisation of Wigner’s theorem on quantum mechanical symmetry transformations, that is considered to be a cornerstone of the mathematical foundations of quantum mechanics. Namely, under the above assumptions, every bijective map on the set of pure states of a quantum mechanical system that preserves the transition probability $\cos ^2\alpha$ in both directions is a Wigner symmetry (thus automatically preserves all transition probabilities), except for the case when $H=\mathbb{C}^2$ and $\alpha = \tfrac{\pi }{4}$ where an additional possibility occurs. (Note that the classical theorem of Uhlhorn is the solution for the $\alpha = \tfrac{\pi }{2}$ case). Usually in the literature, results which are connected to Wigner’s theorem are discussed under the assumption of completeness of H; however, here we shall remove this unnecessary hypothesis in our investigation. Our main tool is a characterisation of bijective maps on unit spheres of real inner product spaces which preserve one spherical angle in both directions.
Medically Indicated Preterm Deliveries – Are Placental Dysfunction and Vasculopathies Related? [9A]
Authors: Boggess Kim A. , Saade George R. , Cousins Larry M. , Coonrod Dean , Lueth Amir J. , Randolph Todd L. 
Published: April 2018

INTRODUCTION:
To examine the relationship between placental dysfunction disorders (PDD), vasculopathies (VP), medically indicated preterm delivery (miPTD) and spontaneous preterm delivery (sPTD).

METHODS:
Retrospective cohort study of women with singleton gestations. Preterm delivery defined as delivery prior to 37 weeks gestation. The type of delivery (term, miPTD, or sPTD) was determined, and clinical diagnoses were categorized into PDD (preeclampsia, fetal distress, IUGR, oligohydramnios, abruption, gestational hypertension) and VP (Type 1 or 2 diabetes, gestational diabetes, chronic hypertension). The prevalence for each diagnosis was examined for each type of delivery.

RESULTS:
Study population included 3049 term deliveries, 190 sPTD, and 232 miPTD. There were no significant differences in maternal age and parity among these three groups. Patients with miPTD were more likely to be non-Hispanic and to have a higher BMI. As expected, the fraction of patients with at least one PDD or VP were significantly higher for miPTB compared to sPTB and term. Also, the fraction of patients with at least one PDD AND at least one VP were markedly and significantly (p less than 0.0001) higher for miPTD (20%) compared to sPTD (4.2%) or term (2.7%). Interestingly, patients with a more severe vasculopathy or multiple concurrent vasculopathies were associated with higher rates of PTD, particularly miPTD.

CONCLUSION:
The combination, PDD/VP, is significantly increased in miPTD versus sPTD or terms, and severe vasculopathies or concurrent vasculopathies show increased rates of PTD. These conditions may indicate severe epithelial damage resulting in poor perfusion and primary placental dysfunction requiring miPTD.
Tracking the Development of Risk Factors for Vascular Disease After Pregnancy with Pre-Eclampsia [16A]
Authors: Wong Adriana J. , Lederer Madeline , Diego Daniela , Nguyen Desiree , Verma Usha , Chaturvedi Seemant 
Published: April 2018

INTRODUCTION:
Women with a history of preeclampsia have a higher lifetime risk for cardiovascular disease and cerebrovascular disease. Therefore, tracking the development of risk factors for heart disease and stroke after preeclampsia is necessary.

METHODS:
This is a retrospective chart review of women who were diagnosed with preeclampsia at Jackson Memorial Hospital between 2012-2013 and subsequently followed up within the Jackson Health System between 2014-2016. EMR’s were reviewed to determine whether these women developed hypertension, hyperlipidemia, migraines, obesity, and diabetes mellitus 2-3 years after an event of preeclampsia and whether these conditions were managed with medication. Descriptive statistics were calculated using SAS statistical software.

RESULTS:
183 women met inclusion criteria (average age of 32.3 years). Controlling for preexisting conditions, 14.2% (22/183) of women with a history of preeclampsia developed hypertension, 3.8% (7/183) developed dyslipidemia, 3.8% (7/183) developed migraine, 3.8% (7/183) developed obesity, and 4.9% (9/183) developed diabetes mellitus within 2-3 years. The mean duration of follow up care was 2.9 years after preeclampsia. 73.6% (42/57) of all hypertensive women were prescribed an antihypertensive medication, 88.9% (16/18) women with diabetes were on pharmacologic therapy, yet 0% (0/10) women with dyslipidemia were prescribed a statin.

CONCLUSION:
During short-term follow-up after pregnancy with preeclampsia, a significant group of women develop risk factors for cardiovascular disease. Not all patients with these risk factors receive optimal care. Our data suggest a need for the development of structured interventions to reduce stroke and myocardial infarction incidence in this population.
Thrombocytosis is a Prognostic Factor in Women Treated with Chemoradiation for Advanced Cervical Cancer [21A]
Authors: Martin Alexandra , Manahan Kelly , Geisler John 
Published: April 2018

INTRODUCTION:
Prior to the addition of chemotherapy to radiation, thrombocytosis was seen as a poor prognostic factor for women with advanced cervical cancer. The objective of this study was to see in the chemoradiation era whether thrombocytosis was still a prognostic factor.

METHODS:
An IRB study was performed analyzing all patients with cervical cancer receiving primary chemoradiation as therapy with a diagnosis between January 1, 2001 and December 31, 2011. Minimum follow up was 30 months. Records were examined for initial platelet count at diagnosis, stage, grade, histology and survival. Only patients receiving chemoradiation with stage IIa-Vb cervical cancer were studied included in the final analysis.

RESULTS:
209 women with cervical cancer were diagnosed with 173 women treated with primary chemoradiation. The most common stage was IIIb (88, 50.9%). The mean platelet counts of those receiving chemoradiation was significantly higher (396k/ml; 95%CI 376-416k) than those with lower stage disease (313k/ml; 292-334k)(p<0.001). Of the 173 patients, 42 (24.3%) had a platelet count > 450k/ml and 24 (13.9%) had a platelet count >500k/ml. Patients who died of disease had significantly higher initial platelet counts (mean 433k/ml; 95%CI 407-458k) than those who were alive at the completion of follow-up (mean 326k/ml; 95%CI 303-350k). None of the patients with an initial platelet count >500k/ml were alive at the time of follow-up.

CONCLUSION:
High platelet count at initial diagnosis is a poor prognostic factor in women with cervical cancer treated by chemoradiation.
Sentinel Lymph Node Mapping in Endometrioid Endometrial Cancer: Does it Work in the Real World? [22A]
Authors: Valieva Olga , Greer Danielle M. , Kram Jessica J. F. , Schmit Eric , Dickson Elizabeth , Kamelle Scott A. 
Published: April 2018

INTRODUCTION:
To investigate the utility of sentinel lymph node mapping (SLNM) for endometrioid endometrial cancer (EEC) in a community setting.

METHODS:
We retrospectively studied women with EEC who underwent hysterectomy plus surgical staging during January 2011-March 2016. Data were extracted from our local Cancer Registry and confirmed via chart review. Patients underwent either traditional lymphadenectomy (TL) or SLNM with subsequent dissection. Mapping was performed following the protocol of Sloan Kettering. Patient characteristics were compared between lymph node (LN) dissection methods using parametric and nonparametric tests. Differences in recurrence risk were assessed via proportional hazards regression.

RESULTS:
A total of 540 patients with EEC were identified: 180 patients underwent TL and 360 patients underwent SLNM. SLNM attempts were successful in 95% of 377 patients (83% with bilateral detection, 12% with unilateral detection). The total number of LNs dissected was significantly greater in the TL versus SLNM group (median 17.0 vs. 5.00; P<0.01), as was the percentage of patients with positive nodes (10.6 vs. 5.83%; P=0.04). Pathology identified patients who underwent TL as higher risk based on standard risk factors, namely greater tumor diameter extent of myometrial invasion and presence of lymphovascular space invasion. Notably, recurrence risk was not associated with dissection method (hazard ratio [HR] 1.04, confidence interval [CI] 0.48-2.27; P=0.91) or number of LNs retrieved (HR 1.01, CI 0.98-1.04; P=0.45).

CONCLUSION:
SLNM was highly successful (95%) in our community setting. For low-risk EEC patients with tumor diameter <50 mm, myometrial invasion <33%, and grade 1-2, SLNM may be a feasible surgical staging option.
Evaluation of Screening and Risk Reducing Surgery for Women Followed in a High Risk Breast/Ovarian Cancer Clinic [25A]
Authors: Stewart Martha E. , Knisely Anne T. , Sullivan Mackenzie W. , Ring Kari L. , Modesitt Susan C. 
Published: April 2018

INTRODUCTION:
Up to 20% of ovarian cancers are attributed to inherited predispositions, however current screening methods (Ca-125 and pelvic ultrasound) do not improve outcomes compared to risk-reducing (RR) surgery. The study objective was to evaluate surgical outcomes of women followed in an academic center’s High-Risk Breast/Ovarian Cancer (HBOC) clinic following RR surgery.

METHODS:
Retrospective chart review of women from the past decade who underwent RR surgery in a HBOC clinic. Surgical outcomes, pathology, pre-operative screening results, and pre-/post-operative cancer diagnoses were evaluated.

RESULTS:
One hundred and eighty-six high risk women were identified with a mean age of 50.2 years and a mean BMI of 28.9 kg/m2 at the time of surgery. The majority (106; 57%) had strong family history of ovarian cancer without an identified mutation but the rest had deleterious mutations (BRCA2-17.7%, BRCA1-15.1%, Lynch 3.2%, or p53 0.5%). The most common procedure was a risk-reducing bilateral salpingo-oophorectomy with or without hysterectomy (RRBSO, 88.7%). All women underwent the SEE-FIM protocol with extensive pathologic analysis which found 2 (0.8%) invasive ovarian cancers (1 ovary/tube carcinosarcoma, 1 granulosa cell), 3 (1.6%) serous tubal intraepithelial carcinomas (STIC), and 1 fallopian tube cancer (0.8%). All tubal pathology was diagnosed in women with documented BRCA mutations. No cancers were found on screening.

CONCLUSION:
Among all high-risk women undergoing RR surgery, about 3% are ultimately diagnosed with a STIC or an ovarian cancer of which none were identified on screening. All STIC and tubal cancers were diagnosed in women with BRCA mutations (6.6% rate).
Multiparameter Single Cell Characterization of Ovarian Intratumor Heterogeneity [29A]
Authors: Beaumont Kristin , Copperman Alan B. , Dottino Peter , Martignetti John , Schadt Eric , Sebra Robert 
Published: April 2018

INTRODUCTION:
Rapid advances in single-cell and deep sequencing technologies has revealed the genetic and functional complexity of bulk tumor tissue, particularly with regard to heterogeneous and clonal composition. This is especially relevant to HGSOC patients, where existing analyses of these tumors have uncovered a high degree of intratumoral heterogeneity. In this work, we present methods for the isolation of single- and multi-cellular batches to better characterize clonal diversity from HGSOC patient-derived cells.

METHODS:
We demonstrate single- and multi-cellular manipulation and sequencing using multiple technologies. Lysed genomic DNA from single or batched cells was characterized using the AmpliSeq 207-target HotSpot and comprehensive 143-target Oncomine cancer panels. Single cell, differential expression was conducted using Chromium high diversity mRNA sequencing.

RESULTS:
We integrate phenotypic and genotypic profiling of single cells to characterize clonal heterogeneity in HGSOC tumors. Specifically, growth kinetics, differential expression, and clonal TP53 mutation profiling will be discussed in the context of primary samples. Analysis of TP53 mutation demonstrated a clear sub-population (31%) of single cells exhibiting >75% mutation frequency, which is much higher than the 25-40% observed in bulk control samples, indicating that a cellular subset likely drives downstream signaling effects. In addition to genetic data, single cell real-time cloning alongside CA125 and HE4 secretion assays were combined.

CONCLUSION:
Collectively, this genomic data was used to identify cellular clonality and address the degree of heterogeneity across HGSOC tumors when compared to bulk sequencing. We illustrate the potential for utilizing single cell sequencing data in the development of future therapeutic interventions.