bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the predictability of cancer evolution
Authors: Hosseini Sayed-Rzgar , Diaz-Uriarte Ramon , Markowetz Florian , Beerenwinkel Niko 
Published: May 2019

Abstract

Motivation
How predictable is the evolution of cancer? This fundamental question is of immense relevance for the diagnosis, prognosis and treatment of cancer. Evolutionary biologists have approached the question of predictability based on the underlying fitness landscape. However, empirical fitness landscapes of tumor cells are impossible to determine in vivo. Thus, in order to quantify the predictability of cancer evolution, alternative approaches are required that circumvent the need for fitness landscapes.

Results
We developed a computational method based on conjunctive Bayesian networks (CBNs) to quantify the predictability of cancer evolution directly from mutational data, without the need for measuring or estimating fitness. Using simulated data derived from &gt;200 different fitness landscapes, we show that our CBN-based notion of evolutionary predictability strongly correlates with the classical notion of predictability based on fitness landscapes under the strong selection weak mutation assumption. The statistical framework enables robust and scalable quantification of evolutionary predictability. We applied our approach to driver mutation data from the TCGA and the MSK-IMPACT clinical cohorts to systematically compare the predictability of 15 different cancer types. We found that cancer evolution is remarkably predictable as only a small fraction of evolutionary trajectories are feasible during cancer progression.

Availability and implementation
https://github.com/cbg-ethz/predictability\_of\_cancer\_evolution

Supplementary information
Supplementary data are available at Bioinformatics online.
ReSimNet: drug response similarity prediction using Siamese neural networks
Authors: Jeon Minji , Park Donghyeon , Lee Jinhyuk , Jeon Hwisang , Ko Miyoung , Kim Sunkyu , Choi Yonghwa , Tan Aik-Choon , Kang Jaewoo 
Published: May 2019

Abstract

Motivation
Traditional drug discovery approaches identify a target for a disease and find a compound that binds to the target. In this approach, structures of compounds are considered as the most important features because it is assumed that similar structures will bind to the same target. Therefore, structural analogs of the drugs that bind to the target are selected as drug candidates. However, even though compounds are not structural analogs, they may achieve the desired response. A new drug discovery method based on drug response, which can complement the structure-based methods, is needed.

Results
We implemented Siamese neural networks called ReSimNet that take as input two chemical compounds and predicts the CMap score of the two compounds, which we use to measure the transcriptional response similarity of the two compounds. ReSimNet learns the embedding vector of a chemical compound in a transcriptional response space. ReSimNet is trained to minimize the difference between the cosine similarity of the embedding vectors of the two compounds and the CMap score of the two compounds. ReSimNet can find pairs of compounds that are similar in response even though they may have dissimilar structures. In our quantitative evaluation, ReSimNet outperformed the baseline machine learning models. The ReSimNet ensemble model achieves a Pearson correlation of 0.518 and a precision@1% of 0.989. In addition, in the qualitative analysis, we tested ReSimNet on the ZINC15 database and showed that ReSimNet successfully identifies chemical compounds that are relevant to a prototype drug whose mechanism of action is known.

Availability and implementation
The source code and the pre-trained weights of ReSimNet are available at https://github.com/dmis-lab/ReSimNet.

Supplementary information
Supplementary data are available at Bioinformatics online.
On the individual surrogate paradox
Authors: Ma Linquan , Yin Yunjian , Liu Lan , Geng Zhi 
Published: May 2019

SUMMARY
When the primary outcome is difficult to collect, a surrogate endpoint is typically used as a substitute. It is possible that for every individual, the treatment has a positive effect on the surrogate, and the surrogate has a positive effect on the primary outcome, but for some individuals, the treatment has a negative effect on the primary outcome. For example, a treatment may be substantially effective in preventing the stroke for everyone, and lowering the risk of stroke is universally beneficial for life expectancy; however, the treatment may still cause death for some individuals. We define such paradoxical phenomenon as the individual surrogate paradox. The individual surrogate paradox is proposed to capture the treatment effect heterogeneity, which is unable to be described by either the surrogate paradox based on average causal effect or that based on distributional causal effect. We investigate the existing surrogate criteria in terms of whether the individual surrogate paradox could manifest. We find that only the strong binary surrogate can avoid such paradox without additional assumptions. Utilizing the sharp bounds, we propose novel criteria to exclude the individual surrogate paradox. Our methods are illustrated in an application to determine the effect of the intensive glycemia on the risk of development or progression of diabetic retinopathy.
Risk stratification of cervical lesions using capture sequencing and machine learning method based on HPV and human integrated genomic profiles
Authors: Tian Rui , Cui Zifeng , He Dan , Tian Xun , Gao Qinglei , Ma Xin , Yang Jian-rong , Wu Jun , Das Bhudev C , Severinov Konstantin , Hitzeroth Inga Isabel , Debata Priya Ranjan , Xu Wei , Zhong Haolin , Fan Weiwen , Chen Yili , Jin Zhuang , Cao Chen , Yu Miao , Xie Weiling , Huang Zhaoyue , Bao Yuxian , Xie Hongxian , Yao Shuzhong , Hu Zheng 
Published: May 2019

Abstract
From initial human papillomavirus (HPV) infection and precursor stages, the development of cervical cancer takes decades. High-sensitivity HPV DNA testing is currently recommended as primary screening method for cervical cancer, whereas better triage methodologies are encouraged to provide accurate risk management for HPV-positive women. Given that virus-driven genomic variation accumulates during cervical carcinogenesis, we designed a 39 Mb custom capture panel targeting 17 HPV types and 522 mutant genes related to cervical cancer. Using capture-based next-generation sequencing, HPV integration status, somatic mutation and copy number variation were analyzed on 34 paired samples, including 10 cases of HPV infection (HPV+), 10 cases of cervical intraepithelial neoplasia (CIN) grade and 14 cases of CIN2+ (CIN2: n = 1; CIN2-3: n = 3; CIN3: n = 9; squamous cell carcinoma: n = 1). Finally, the machine learning algorithm (Random Forest) was applied to build the risk stratification model for cervical precursor lesions based on CIN2+ enriched biomarkers. Generally, HPV integration events (11 in HPV+, 25 in CIN1 and 56 in CIN2+), non-synonymous mutations (2 in CIN1, 12 in CIN2+) and copy number variations (19.1 in HPV+, 29.4 in CIN1 and 127 in CIN2+) increased from HPV+ to CIN2+. Interestingly, ‘common’ deletion of mitochondrial chromosome was significantly observed in CIN2+ (P = 0.009). Together, CIN2+ enriched biomarkers, classified as HPV information, mutation, amplification, deletion and mitochondrial change, successfully predicted CIN2+ with average accuracy probability score of 0.814, and amplification and deletion ranked as the most important features. Our custom capture sequencing combined with machine learning method effectively stratified the risk of cervical lesions and provided valuable integrated triage strategies.
Hepatitis B Core-related Antigen: An Alternative to Hepatitis B Virus DNA to Assess Treatment Eligibility in Africa
Authors: Shimakawa Yusuke , Ndow Gibril , Njie Ramou , Njai Harr Freeya , Takahashi Kazuaki , Akbar Sheikh Mohammad Fazle , Cohen Damien , Nayagam Shevanthi , Jeng Adam , Ceesay Amie , Sanneh Bakary , Baldeh Ignatius , Imaizumi Masayasu , Moriyama Kazushige , Aoyagi Katsumi , D’Alessandro Umberto , Mishiro Shunji , Chemin Isabelle , Mendy Maimuna , Thursz Mark R , Lemoine Maud 
Published: May 2019

Abstract

Background
To eliminate hepatitis B virus (HBV) infection, it is essential to scale up testing and treatment. However, conventional tools to assess treatment eligibility, particularly nucleic acid testing (NAT) to quantify HBV DNA, are hardly available and affordable in resource-limited countries. We therefore assessed the performance of a novel immunoassay, hepatitis B core-related antigen (HBcrAg), as an inexpensive (US$ &lt;15/assay) alternative to NAT to diagnose clinically important HBV DNA thresholds (≥2000, ≥20 000, and ≥200 000 IU/mL) and to select patients for antiviral therapy in Africa.

Methods
Using a well-characterized cohort of treatment-naive patients with chronic HBV infection in The Gambia, we evaluated the accuracy of serum HBcrAg to diagnose HBV DNA levels and to indicate treatment eligibility determined by the American Association for the Study of Liver Diseases, based on reference tests (HBV DNA, hepatitis B e antigen, alanine aminotransferase, liver histopathology, and/or FibroScan).

Results
A total of 284 treatment-naive patients were included in the analysis. The area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of serum HBcrAg were 0.88 (95% confidence interval [CI], .82–.93), 83.3%, and 83.9%, respectively, to diagnose HBV DNA ≥2000 IU/mL; and 0.94 (95% CI, .88–.99), 91.4%, and 93.2% for ≥200 000 IU/mL. A simplified treatment algorithm using HBcrAg without HBV DNA showed high AUROC (0.91 [95% CI, .88–.95]) with a sensitivity of 96.6% and specificity of 85.8%.

Conclusions
HBcrAg might be an accurate alternative to HBV DNA quantification as a simple and inexpensive tool to identify HBV-infected patients in need of antiviral therapy in low- and middle-income countries.
An N-/L-type calcium channel blocker, cilnidipine, suppresses autonomic, electrical, and structural remodelling associated with atrial fibrillation
Authors: Tajiri Kazuko , Guichard Jean-Baptiste , Qi Xiaoyan , Xiong Feng , Naud Patrice , Tardif Jean-Claude , Costa Antoine Da , Aonuma Kazutaka , Nattel Stanley 
Published: May 2019

Abstract

Aims
Autonomic dysfunction can promote atrial fibrillation (AF) and results from AF-related remodelling. N-type Ca2+-channels (NTCCs) at sympathetic nerve terminals mediate Ca2+-entry that triggers neurotransmitter release. AF-associated remodelling plays an important role in AF pathophysiology but the effects of NTCC inhibition on such remodelling is unknown. Here, we investigated the ability of a clinically available Ca2+-channel blocker (CCB) with NTCC-blocking activity to suppress the arrhythmogenic effects of AF-promoting remodelling in dogs.

Methods and results
Mongrel dogs were kept in AF by right atrial tachypacing at 600 bpm. Four groups were studied under short-term AF (7 days): (i) Shams, instrumented but without tachypacing (n = 5); (ii) a placebo group, tachypaced while receiving placebo (n = 6); (iii) a control tachypacing group receiving nifedipine (10 mg orally twice-daily; n = 5), an L-type CCB; and (iv) a cilnidipine group, subjected to tachypacing and treatment with cilnidipine (10 mg orally twice-daily; n = 7), an N-/L-type CCB. With cilnidipine therapy, dogs with 1-week AF showed significantly reduced autonomic changes reflected by heart rate variability (decreases in RMSSD and pNN50) and plasma norepinephrine concentrations. In addition, cilnidipine-treated dogs had decreased extracellular matrix gene expression vs. nifedipine-dogs. As in previous work, atrial fibrosis had not yet developed after 1-week AF, so three additional groups were studied under longer-term AF (21 days): (i) Shams, instrumented without tachypacing or drug therapy (n = 8); (ii) a placebo group, tachypaced while receiving placebo (n = 8); (iii) a cilnidipine group, subjected to tachypacing during treatment with cilnidipine (10 mg twice-daily; n = 8). Cilnidipine attenuated 3-week AF effects on AF duration and atrial conduction, and suppressed AF-induced increases in fibrous-tissue content, decreases in connexin-43 expression and reductions in sodium-channel expression.

Conclusions
Cilnidipine, a commercially available NTCC-blocking drug, prevents AF-induced autonomic, electrical and structural remodelling, along with associated AF promotion.
Atorvastatin enhances the therapeutic efficacy of mesenchymal stem cells-derived exosomes in acute myocardial infarction via up-regulating long non-coding RNA H19
Authors: Huang Peisen , Wang Li , Li Qing , Tian Xiaqiu , Xu Jun , Xu Junyan , Xiong Yuyan , Chen Guihao , Qian Haiyan , Jin Chen , Yu Yuan , Cheng Ke , Qian Li , Yang Yuejin 
Published: May 2019

AbstractAimsNaturally secreted nanovesicles, known as exosomes, play important roles in stem cell-mediated cardioprotection. We have previously demonstrated that atorvastatin (ATV) pretreatment improved the cardioprotective effects of mesenchymal stem cells (MSCs) in a rat model of acute myocardial infarction (AMI). The aim of this study was to investigate if exosomes derived from ATV-pretreated MSCs exhibit more potent cardioprotective function in a rat model of AMI and if so to explore the underlying mechanisms.Methods and resultsExosomes were isolated from control MSCs (MSC-Exo) and ATV-pretreated MSCs (MSCATV-Exo) and were then delivered to endothelial cells and cardiomyocytes in vitro under hypoxia and serum deprivation (H/SD) condition or in vivo in an acutely infarcted Sprague-Dawley rat heart. Regulatory genes and pathways activated by ATV pretreatment were explored using genomics approaches and functional studies. In vitro, MSCATV-Exo accelerated migration, tube-like structure formation, and increased survival of endothelial cells but not cardiomyocytes, whereas the exosomes derived from MSCATV-Exo-treated endothelial cells prevented cardiomyocytes from H/SD-induced apoptosis. In a rat AMI model, MSCATV-Exo resulted in improved recovery in cardiac function, further reduction in infarct size and reduced cardiomyocyte apoptosis compared to MSC-Exo. In addition, MSCATV-Exo promoted angiogenesis and inhibited the elevation of IL-6 and TNF-α in the peri-infarct region. Mechanistically, we identified lncRNA H19 as a mediator of the role of MSCATV-Exo in regulating expression of miR-675 and activation of proangiogenic factor VEGF and intercellular adhesion molecule-1. Consistently, the cardioprotective effects of MSCATV-Exo was abrogated when lncRNA H19 was depleted in the ATV-pretreated MSCs and was mimicked by overexpression of lncRNA H19.ConclusionExosomes obtained from ATV-pretreated MSCs have significantly enhanced therapeutic efficacy for treatment of AMI possibly through promoting endothelial cell function. LncRNA H19 mediates, at least partially, the cardioprotective roles of MSCATV-Exo in promoting angiogenesis.
The Long-Run Effects of Oil Wealth on Development: Evidence from Petroleum Geology
Authors: Cassidy Traviss 
Published: May 2019

Abstract
We estimate the long-run effects of oil wealth on development by exploiting spatial variation in sedimentary basins—areas where petroleum can potentially form. Instrumental variables estimates indicate that oil production impedes democracy and fiscal capacity development, increases corruption, and raises GDP per capita without significantly harming the non-resource sectors of the economy. We find no evidence that oil production increases internal armed conflict, coup attempts, or political purges. In several specifications failure to account for endogeneity leads to substantial underestimation of the adverse effects of oil, suggesting that countries with higher-quality political institutions and greater fiscal capacity disproportionately select into oil production.
The Causal Effect of Military Conscription on Crime*
Authors: Hjalmarsson Randi , Lindquist Matthew J 
Published: May 2019

AbstractWe study the causal effect of mandatory military conscription in Sweden on the criminal behaviour of men born in the 1970s. We find that military service significantly increases post-service crime (overall and across multiple crime categories) between the ages of 23 and 30. These results are driven primarily by young men who come from low socioeconomic status households and those with pre-service criminal histories, despite evidence of a contemporaneous incapacitation effect of service for the latter group. Much of this crime-inducing effect can be attributed to negative peer effects experienced during service. Worse post-service labour market outcomes may also matter.
Approaching Earth’s core conditions in high-resolution geodynamo simulations
Authors: Aubert Julien 
Published: May 2019

SUMMARY
The geodynamo features a broad separation between the large scale at which Earth’s magnetic field is sustained against ohmic dissipation and the small scales of the turbulent and electrically conducting underlying fluid flow in the outer core. Here, the properties of this scale separation are analysed using high-resolution numerical simulations that approach closer to Earth’s core conditions than earlier models. The new simulations are obtained by increasing the resolution and gradually relaxing the hyperdiffusive approximation of previously published low-resolution cases. This upsizing process does not perturb the previously obtained large-scale, leading-order quasi-geostrophic (QG) and first-order magneto-Archimedes-Coriolis (MAC) force balances. As a result, upsizing causes only weak transients typically lasting a fraction of a convective overturn time, thereby demonstrating the efficiency of this approach to reach extreme conditions at reduced computational cost. As Earth’s core conditions are approached in the upsized simulations, Ohmic losses dissipate up to 97 per cent of the injected convective power. Kinetic energy spectra feature a gradually broadening self-similar, power-law spectral range extending over more than a decade in length scale. In this range, the spectral energy density profile of vorticity is shown to be approximately flat between the large scale at which the magnetic field draws its energy from convection through the QG-MAC force balance and the small scale at which this energy is dissipated. The resulting velocity and density anomaly planforms in the physical space consist in large-scale columnar sheets and plumes, respectively, co-existing with small-scale vorticity filaments and density anomaly ramifications. In contrast, magnetic field planforms keep their large-scale structure after upsizing. The small-scale vorticity filaments are aligned with the large-scale magnetic field lines, thereby minimizing the dynamical influence of the Lorentz force. The diagnostic outputs of the upsized simulations are more consistent with the asymptotic QG-MAC theory than those of the low-resolution cases that they originate from, but still feature small residual deviations that may call for further theoretical refinements to account for the structuring constraints of the magnetic field on the flow.
The Limitations on Article 43 ICSID Convention: An (Un)limited Instrument of the Tribunal?
Authors: Niemoj Asaf 
Published: May 2019

Abstract
Article 43 of the ICSID Convention provides tribunals with the power to order the production of further evidence. Although that power has not been used frequently, previous cases show that when article 43 is invoked by tribunals, they seem to err in the way in which they use it. This leads to a lack of consistency and clarity in the application of the provision.
This article examines the use of article 43 in two types of cases and suggests two limitations on its use. First, it examines cases in which article 43 was used by tribunals to appoint an independent expert and shows that the provision cannot be used by tribunals to do so.
Second, it looks at scenarios in which article 43 was used by tribunals in a way that added disputed questions, which were not part of the parties’ submissions and which consequently expanded the boundaries of the dispute. It suggests that article 43 cannot be invoked when that is the case. To reach this conclusion, the article will examine cases in which the use of article 43 was considered in order to investigate allegations of corruption.
Article 29—Awards, Orders, Decisions, and Rulings
Authors: Gusy Martin F , Hosking James M 
Published: May 2019

Abstract
This chapter addresses Article 29 of the ICDR Rules. In any arbitration, the tribunal will almost always be required to take certain decisions before it is tasked with rendering a final award. Article 29 provides the tribunal with the broad authority to make such decisions to keep the arbitration advancing and to ultimately resolve the dispute. In addition to the broad powers in Article 29(1), Article 29(2) attempts to address the possibility that a unanimous decision will be unobtainable in an arbitration involving more than a sole arbitrator by permitting any ‘award, order, decision, or ruling’ to be made by a majority of arbitrators, regardless of whether the presiding arbitrator is part of that majority. Meanwhile, Article 29(3) empowers the tribunal to delegate to the presiding arbitrator the authority to make ‘orders, decisions, or rulings on questions of procedure’, subject to revision by the full tribunal.
The African Charter on Human and Peoples' Rights
Authors: Murray Rachel 
Published: May 2019

Abstract
The African Charter on Human and Peoples’ Rights (ACHPR) is the principle regional human rights treaty for the African continent. Adopted in 1981, there is now a significant body of jurisprudence and interpretation by its African Commission on Human and Peoples’ Rights and the recently established African Court. This volume provides a comprehensive article-by-article legal analysis of the provisions of the Charter as it draws upon the documents adopted by the African Commission, including resolutions, case law, and concluding observations. Where relevant, case law adopted by the African Court on Human and Peoples’ Rights, and that of other sub-regional courts and tribunals and domestic courts in Africa, are also incorporated. The book examines not only the substantive rights in the African Charter but also the work of the African Commission on Human and Peoples’ Rights and provides a full examination of its mandate. A critical analysis of each of the provisions of the ACHPR is led principally by the jurisprudence and documentation of the African Commission and African Court. The text also identifies the overall development of the ACHPR within the broader regional and international human rights legal arena.
Using convolutional neural networks to identify gravitational lenses in astronomical images
Authors: Davies Andrew , Serjeant Stephen , Bromley Jane M 
Published: May 2019

Abstract
The Euclid telescope, due for launch in 2021, will perform an imaging and slitless spectroscopy survey over half the sky, to map baryon wiggles and weak lensing. During the survey, Euclid is expected to resolve 100 000 strong gravitational lens systems. This is ideal to find rare lens configurations, provided they can be identified reliably and on a reasonable time-scale. For this reason, we have developed a convolutional neural network (CNN) that can be used to identify images containing lensing systems. CNNs have already been used for image and digit classification as well as being used in astronomy for star-galaxy classification. Here, our CNN is trained and tested on Euclid-like and KiDS (Kilo-Degree Survey)-like simulations from the Euclid Strong Lensing Group, successfully classifying 77 per cent of lenses, with an area under the ROC curve of up to 0.96. Our CNN also attempts to classify the lenses in COSMOS Hubble Space Telescope F814W-band images. After convolution to the Euclid resolution, we find we can recover most systems that are identifiable by eye. The python code is available on Github.