bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHROMOSOMAL AND NONCHROMOSOMAL MUTATIONS AFFECTING THE "KILLER CHARACTER" OF SACCHAROMYCES CEREVISIAE
Authors: Wickner Reed B 
Published: January 2021

ABSTRACT
The "killer character" of Saccharomyces cerevisiae is a nonchromosomal genetic element which imparts to cells carrying it (a) the ability to kill cells which lack it, by secreting the soluble macromolecular killer substance and (b) the ability to resist the killing effects of the killer substance.—Mutants have been isolated from S. cerevisiae carrying the "killer character". Mutants were found in two nuclear genes (mak1 and mak2) involved in maintenance of the genetic element of the killer character. Mutants in three other nuclear genes could maintain the cytoplasmic genetic element normally; two of these were able to express resistance to killing, but not the ability to kill (kex1 and kex2), while the third could express the killing function, but was sensitive to killing and is thus a "suicide" strain (rex1). These five nuclear genes were all distinct.—Several mutants were detected which showed non—mendelian segregation indicating mutation of the "cytoplasmic" genetic element. Some such mutants had normal resistance to killing but were either unable to kill at all or showed marked reduction in the ability to kill. Others had lost both killing ability and resistance. None were suppressive.—Two nonkilling mutants, both of which showed cytoplasmic inheritance, were mated. A large, but variable, proportion of diploid colonies, plated after several generations of growth, showed normal killing which has then stably inherited on further subcloning.
SELECTION FOR REDUCED CROSSING OVER IN DROSOPHILA MELANOGASTER
Authors: Abdullah Nasr F , Charlesworth Brian 
Published: January 2021

ABSTRACT
Selection was practiced for reducing crossing over between the third chromosome genes Sb and H2 of Drosophila melanogaster, the method employed was to select the repulsion double heterozygotes Sb+/+H2 every generation. Two replicate selection lines were maintained. After 24 generations of selection, Line 1 showed no significant difference from the control, although the regression of recombination value on generation was significant. In generation 20, Line 2 had a significantly lower recombination value than the control, as well as having a highly significant regression coefficient. No chromosome rearrangements were involved in the response. It was concluded that there was substantial genic variability in the frequency of crossing over between Sb and H2 in the base population.
Tool recommender system in Galaxy using deep learning
Authors: Kumar Anup , Rasche Helena , Grüning Björn , Backofen Rolf 
Published: January 2021

Abstract

Background
Galaxy is a web-based and open-source scientific data-processing platform. Researchers compose pipelines in Galaxy to analyse scientific data. These pipelines, also known as workflows, can be complex and difficult to create from thousands of tools, especially for researchers new to Galaxy. To help researchers with creating workflows, a system is developed to recommend tools that can facilitate further data analysis.

Findings
A model is developed to recommend tools using a deep learning approach by analysing workflows composed by researchers on the European Galaxy server. The higher-order dependencies in workflows, represented as directed acyclic graphs, are learned by training a gated recurrent units neural network, a variant of a recurrent neural network. In the neural network training, the weights of tools used are derived from their usage frequencies over time and the sequences of tools are uniformly sampled from training data. Hyperparameters of the neural network are optimized using Bayesian optimization. Mean accuracy of 98% in recommending tools is achieved for the top-1 metric.

Conclusions
The model is accessed by a Galaxy API to provide researchers with recommended tools in an interactive manner using multiple user interface integrations on the European Galaxy server. High-quality and highly used tools are shown at the top of the recommendations. The scripts and data to create the recommendation system are available under MIT license at https://github.com/anuprulez/galaxy_tool_recommendation.
Reducing Stunting through Multisectoral Efforts in Sub-Saharan Africa
Authors: Skoufias Emmanuel , Vinha Katja , Sato Ryoko 
Published: January 2021

Abstract
This paper lays the groundwork for more effective multisectoral action on reducing stunting, by analysing and generating empirical evidence useful for informing the joint targeting of nutrition-sensitive interventions in the countries in Sub-Saharan Africa. Using information from 33 recent Demographic and Health Surveys, measures are constructed to capture a child’s access to food security, care practices, healthcare and water, sanitation and hygiene (WASH), in order to identify gaps in access among different socio-economic groups and relate access to these nutrition drivers with nutrition outcomes. Three main questions are addressed. (a) What is the extent to which children have inadequate access to the underlying determinants of nutrition? (b) What is the association between stunting and overlapping deprivations in adequate food and care practices, health and WASH services? (c) What are the sectors that have the greatest impact on stunting?
Factors Associated With Health-Related Quality of Life Among Cancer Survivors in the United States
Authors: Han Xuesong , Robinson L Ashley , Jensen Roxanne E , Smith Tenbroeck G , Yabroff K Robin 
Published: January 2021

Abstract

Background
With increasing prevalence of cancer survivors in the United States, health-related quality of life (HRQOL) has become a major priority. We describe HRQOL in a nationally representative sample of cancer survivors and examine associations with key sociodemographic, clinical, and lifestyle characteristics.

Methods
Cancer survivors, defined as individuals ever diagnosed with cancer (N = 877), were identified from the 2016 Medical Expenditure Panel Survey-Experiences with Cancer Survivorship Supplement, a nationally representative survey. Physical and mental health domains of HRQOL were measured by the Global Physical Health (GPH) and Global Mental Health (GMH) subscales of the Patient-Reported Outcomes Measurement Information System Global-10. Multivariable linear regression was used to examine associations of sociodemographic, clinical, and lifestyle factors with GPH and GMH scores. All statistical tests were 2-sided.

Results
Cancer survivors’ mean GPH (49.28, SD = 8.79) and mean GMH (51.67, SD = 8.38) were similar to general population means (50, SD = 10). Higher family income was associated with better GPH and GMH scores, whereas a greater number of comorbidities and lower physical activity were statistically significantly associated with worse GPH and GMH. Survivors last treated 5 years ago and longer had better GPH than those treated during the past year, and current smokers had worse GMH than nonsmokers (all β &gt; 3 and all P &lt; .001).

Conclusions
Cancer survivors in the United States have generally good HRQOL, with similar physical and mental health scores to the general US population. However, comorbidities, poor health behaviors, and recent treatment may be risk factors for worse HRQOL. Multimorbidity management and healthy behavior promotion may play a key role in maximizing HRQOL for cancer survivors.
Arbitral Jurisdictional Regulation in Investment Treaty Arbitration and Domestic Courts
Authors: Radović Relja 
Published: January 2021

Abstract
Arbitral tribunals in the field of investment treaty arbitration have generated rules governing their own jurisdiction. This article examines the effect of the controlling role of domestic courts on the development of arbitral jurisdictional regulation, tracking the treatment of arbitrator-made jurisdictional rules by domestic courts reviewing investment arbitral decisions. The article finds that domestic courts have not been resistant to but rather supportive of the proliferation of arbitrator-made jurisdictional rules. First, domestic courts have relied on such rules and treated their development as parts of interpretative exercises and as part of the arbitral judicial function. Second, domestic courts have engaged in discourses on the appropriateness of arbitrator-made jurisdictional rules in substance. This practice contradicts the expectation that domestic courts would contest arbitral jurisdictional regulation and shows the potential of domestic courts to contribute to the production of nuanced rules governing the jurisdiction of investment arbitral tribunals.
Intersection between Domestic Violence and International Parental Child Abduction: Protection of Abducting Mothers in Return Proceedings
Authors: Trimmings Katarina , Momoh Onyója 
Published: January 2021

Abstract
The focus of the article is on the intersection between domestic violence and parental child abduction, in particular, the interpretation of the Article 13(1)(b) ‘grave risk of harm’ defence in cases involving allegations of domestic violence by the abducting mother against the left-behind father, and on the protection of such abducting mothers in return proceedings. The content of the article is divided into two substantive parts. The first part explores the courts' approach to the grave risk of harm exception to return in circumstances where allegations of domestic violence have been raised. The second part of the article examines the courts' approach to protective measures, including undertakings, in child abduction cases involving allegations of domestic violence. The article engages extensively with the work of the Hague Conference on Private International Law and the EU in the area of international parental child abduction, as inter alia, it explores the problem of effectiveness of protective measures with reference to the 1996 Hague Convention on Jurisdiction, Applicable Law, Recognition, Enforcement and Co-operation in Respect of Parental Responsibility and Measures for the Protection of Children and the Regulation 606/2013 on mutual recognition of protection measures in civil matters.
BRAKER2: automatic eukaryotic genome annotation with GeneMark-EP+ and AUGUSTUS supported by a protein database
Authors: Brůna Tomáš , Hoff Katharina J , Lomsadze Alexandre , Stanke Mario , Borodovsky Mark 
Published: January 2021

AbstractThe task of eukaryotic genome annotation remains challenging. Only a few genomes could serve as standards of annotation achieved through a tremendous investment of human curation efforts. Still, the correctness of all alternative isoforms, even in the best-annotated genomes, could be a good subject for further investigation. The new BRAKER2 pipeline generates and integrates external protein support into the iterative process of training and gene prediction by GeneMark-EP+ and AUGUSTUS. BRAKER2 continues the line started by BRAKER1 where self-training GeneMark-ET and AUGUSTUS made gene predictions supported by transcriptomic data. Among the challenges addressed by the new pipeline was a generation of reliable hints to protein-coding exon boundaries from likely homologous but evolutionarily distant proteins. In comparison with other pipelines for eukaryotic genome annotation, BRAKER2 is fully automatic. It is favorably compared under equal conditions with other pipelines, e.g. MAKER2, in terms of accuracy and performance. Development of BRAKER2 should facilitate solving the task of harmonization of annotation of protein-coding genes in genomes of different eukaryotic species. However, we fully understand that several more innovations are needed in transcriptomic and proteomic technologies as well as in algorithmic development to reach the goal of highly accurate annotation of eukaryotic genomes.
Clinical, molecular, metabolic, and immune features associated with oxidative phosphorylation in melanoma brain metastases
Authors: Fischer Grant M , Guerrieri Renato A , Hu Qianghua , Joon Aron Y , Kumar Swaminathan , Haydu Lauren E , McQuade Jennifer L , Vashisht Gopal Y N , Knighton Barbara , Deng Wanleng , Hudgens Courtney W , Lazar Alexander J , Tetzlaff Michael T , Davies Michael A 
Published: January 2021

AbstractBackgroundRecently, we showed that melanoma brain metastases (MBMs) are characterized by increased utilization of the oxidative phosphorylation (OXPHOS) metabolic pathway compared to melanoma extracranial metastases (ECMs). MBM growth was inhibited by a potent direct OXPHOS inhibitor, but observed toxicities support the need to identify alternative therapeutic strategies. Thus, we explored the features associated with OXPHOS to improve our understanding of the pathogenesis and potential therapeutic vulnerabilities of MBMs.MethodsWe applied an OXPHOS gene signature to our cohort of surgically resected MBMs that had undergone RNA-sequencing (RNA-seq) (n = 88). Clustering by curated gene sets identified MBMs with significant enrichment (High-OXPHOS; n = 21) and depletion (Low-OXPHOS; n = 25) of OXPHOS genes. Clinical data, RNA-seq analysis, and immunohistochemistry were utilized to identify significant clinical, molecular, metabolic, and immune associations with OXPHOS in MBMs. Preclinical models were used to further compare melanomas with High- and Low-OXPHOS and for functional validation.ResultsHigh-OXPHOS MBMs were associated with shorter survival from craniotomy compared to Low-OXPHOS MBMs. High-OXPHOS MBMs exhibited an increase in glutamine metabolism, and treatment with the glutaminase inhibitor CB839 improved survival in mice with MAPKi-resistant, High-OXPHOS intracranial xenografts. High-OXPHOS MBMs also exhibited a transcriptional signature of deficient immune activation, which was reversed in B16-F10 intracranial tumors with metformin treatment, an OXPHOS inhibitor.ConclusionsOXPHOS is associated with distinct clinical, molecular, metabolic, and immune phenotypes in MBMs. These associations suggest rational therapeutic strategies for further testing to improve outcomes in MBM patients.
A novel loss-of-function mutation in LACC1 underlies hereditary juvenile arthritis with extended intra-familial phenotypic heterogeneity
Authors: Butbul Aviel Yonatan , Ofir Ayala , Ben-Izhak Ofer , Vlodavsky Euvgeni , Karbian Netanel , Brik Riva , Mevorach Dror , Magen Daniella 
Published: January 2021

Abstract

Objective
To investigate phenotypic and molecular characteristics of a consanguineous family with autosomal-recessive, polyarticular, juvenile isiopathic arthriris (JIA) with extra-articular manifestations, including renal amyloidosis and Crohn’s disease, associated with a novel homozygous truncating variant in LACC1.

Methods
Whole exome sequencing (WES) or targeted Sanger verification were performed in 15 participants. LACC1 expression and cytokine array were analysed in patient-derived and CRISPR/Cas9-generated LACC1-knockout macrophages (Mϕ).

Results
A homozygous truncating variant (p.Glu348Ter) in LACC1 was identified in three affected and one asymptomatic family member, and predicted harmful by causing premature stop of the LACC1 protein sequences, and by absence from ethnically-matched controls and public variation databases. Expression studies in patient-derived macrophages (Mϕ) showed no endogenous p.Glu348Ter-LACC1 RNA transcription or protein expression, compatible with nonsense-mediated mRNA decay. WES analysis in the asymptomatic homozygous subject for p. Glu348Ter-LACC1 detected an exclusive heterozygous variant (p.Arg928Gln) in complement component C5. Further complement activity analysis suggested a protective role for the p.Arg928Gln-C5 variant as a phenotypic modifier of LACC1-associated disease. Finally, cytokine profile analysis indicated increased levels of pro-inflammatory cytokines in LACC1-disrupted as compared with wild-type Mϕ.

Conclusions
Our findings reinforce the role of LACC1 disruption in autosomal-recessive JIA, extend the clinical spectrum and intra-familial heterogeneity of the disease-associated phenotype, indicate a modulatory effect of complement factor C5 on phenotypic severity, and suggest an inhibitory role for wild-type LACC1 on pro-inflammatory pathways.
Rapid online teaching: movement of animal science courses online during COVID-19. Case study: pedagogical decisions in transitioning animal science courses online
Authors: Barnes Taylor L , Ramsey W Shawn , Dunlap Kathrin A 
Published: January 2021

Abstract
Traditionally, earning a degree in animal science requires many face-to-face, hands-on courses; however, the COVID-19 pandemic created a situation in which traditional delivery of these courses may not be feasible as they provide a health risk to our students, teaching assistants, and instructors alike. This examination of two pedagogically different courses and how each was transitioned to an online format highlights the types of teaching decisions that are required to effectively teach animal science in an online format. The Farm Animal Production Systems lab was an animal handling and production practices lab, and although the transition to online delivery did not allow for students to participate in traditional hands-on development of skills, various resources were utilized that still achieved the development of animal handling concepts that will prepare students for later courses and work with live animals. In contrast, the Animal Science Laboratory Teaching Methods course remained consistent in format through the transition to online because students were still able to participate in discussion-based activities via Zoom meetings each week due to the small class size, which helped to maintain student engagement. However, the final teaching experience was modified to an alternative assignment. The alternate assignment included self-reflection and course evaluation that will help to improve both the Farm Animal Production Systems laboratory and the Animal Science Teaching Methods course in the future. Although COVID-19 has been a challenge that disrupted traditional courses, it has provided opportunities for a traditionally hands-on discipline, such as animal science, to more effectively engage students via an online platform.
The Demand for Advice: Theory and Empirical Evidence from Farmers in Sub-Saharan Africa
Authors: Naeher Dominik , Schündeln Matthias 
Published: January 2021

Abstract
Low levels of investment into modern technologies, and limited use of measures that have low monetary cost but the potential for high yields, are often regarded as obstacles to further agricultural development. This paper investigates farmers’ demand for one such measure, namely agricultural advisory services. These have modest (most frequently zero) monetary user cost but, according to some recent research, have the potential to result in large increases of yields. Yet demand for these extension services is often low. We propose that costly attention may be part of the explanation for this. In our model, advisory services are available free of charge, but positive effects on production are only realized if farmers devote attention to listening to and implementing the provided advice. Modeling farmers as rational decision makers facing scarce attention, we identify the circumstances under which farmers may optimally abstain from demanding advisory services. The model complements the insights of other theories commonly used to explain suboptimal farm decisions and outcomes, and generates testable predictions, which are consistent with empirical evidence based on a large farm-level panel dataset from Sub-Saharan Africa.
Pregnancy Loss and Cardiovascular Disease: A Nationwide Cohort Study
Authors: Mikkelsen Anders P. , Egerup Pia , Kolte Astrid M. , Westergaard David , Torp-Pedersen Christian , Nielsen Henriette S. , Lidegaard øjvind 
Published: January 2021

AbstractObjectivesTo examine how pregnancy loss influences the risk of cardiovascular disease later in life.DesignProspective historical cohort study.SettingDanish nationwide health registries.ParticipantsAll Danish women with a recorded pregnancy from 1977 to 2017.Main outcome measuresVenous thromboembolism, myocardial infarction, or ischemic stroke.ResultsIn this two-part study, part one evaluated the 20-year absolute risk of cardiovascular disease from age 40 among 596,699 women with a full registered reproductive history. Adjusting for calendar year, diabetes, autoimmune disease, live births, and education, the absolute risk of an outcome after 0 and ≥4 pregnancy losses, respectably was: venous thromboembolism 3.0% (95% CI 2.8 to 3.2%) and 5.0% (3.4 to 6.8%); myocardial infarction 1.5% (1.4 to 1.6%) and 2.4% (1.4 to 3.6%); ischemic stroke 2.0% (1.9 to 2.1%) and 2.6% (1.5 to 3.6%). Prior stillbirth increased the absolute risk of later venous thromboembolism by 1.1% (0.2 to 2.3%); myocardial infarction by 1.1% (0.3 to 2.0%).In study part two, we included 966,490 women from first pregnancy in a time-dependent Cox regression model. Adjusted for confounders, each additional pregnancy loss increased the hazard ratio of venous thromboembolism 1.10 (95% CI 1.07 to 1.13); myocardial infarction 1.12 (1.07 to 1.18); and ischemic stroke 1.10 (1.06 to 1.14). Stillbirth was strongly associated with myocardial infarction before age 40, adjusted hazard ratio of 4.60 (2.65 to 8.00).ConclusionPregnancy loss was associated with later venous thromboembolism, myocardial infarction, and ischemic stroke. The absolute and relative risk of outcomes increased in a dose-response manner with increasing numbers of prior pregnancy losses. Stillbirth was strongly associated with myocardial infarction before age 40.
Prostate cancer resistance leads to a global deregulation of translation factors and unconventional translation of long non-coding RNAs
Authors: Lelong Emeline I. J. , Adjibade Pauline , Joncas France-Hélène , Khelifi Gabriel , Grenier Valerie ST.-Sauveur , Zoubedi Amina , Lambert Jean-Philippe , Toren Paul , Mazroui Rachid , Hussein Samer M. I. 
Published: January 2021

ABSTRACTEmerging evidence associates translation factors and regulators to tumorigenesis. Recent advances in our ability to perform global translatome analyses indicate that our understanding of translational changes in cancer resistance is still limited. Here, we generated an enzalutamide-resistant prostate cancer (PCa) model, which recapitulated key features of clinical enzalutamide-resistant PCa. Using this model and polysome profiling, we investigated global translation changes that occur during the acquisition of PCa resistance. We found that enzalutamide-resistant cells exhibit a discordance in biological pathways affected in their translatome relative to their transcriptome, a deregulation of proteins involved in translation, and an overall decrease in translational efficiency. We also show that genomic alterations in proteins with high translational efficiency in enzalutamide-resistant cells are good predictors of poor patient prognosis. Additionally, long non-coding RNAs in enzalutamide-resistant cells show increased association with ribosomes, higher translation efficiency, and an even stronger correlation with poor patient prognosis. Taken together, this suggests that aberrant translation of coding and non-coding genes are strong indicators of PCa enzalutamide-resistance. Our findings thus point towards novel therapeutic avenues that may target enzalutamide resistant PCa.