bluuebunny/crossref_metadata_2025_split huggingface dataset:
Belimumab after B cell depletion therapy in patients with systemic lupus erythematosus (BEAT Lupus) protocol: a prospective multicentre, double-blind, randomised, placebo-controlled, 52-week phase II clinical trial
Authors: Jones Alexis , Muller Patrick , Dore Caroline J , Ikeji Felicia , Caverly Emilia , Chowdhury Kashfia , Isenberg David A , Gordon Caroline , Ehrenstein Michael R 
Published: December 2019

IntroductionFew treatment options exist for patients with systemic lupus erythematosus (SLE) who fail conventional therapy. Although widely used to treat lupus, the efficacy of B cell depletion therapy using rituximab has not been demonstrated in randomised clinical trials. Following rituximab, elevated levels of serum B cell activating factor (BAFF) have been associated with failure to remit or subsequent lupus relapse. The administration of belimumab, a monoclonal antibody specific for BAFF and approved for lupus therapy, could potentiate the efficacy of rituximab and enable longer periods of disease remission. The aim of this trial is to assess the safety and efficacy of belimumab following rituximab in patients with SLE.Methods and analysisBEAT Lupus is a double-blind, randomised, placebo controlled, phase II clinical trial. Patients with SLE commencing a treatment cycle of rituximab (two 1g infusions, 2 weeks apart) as standard of care will be randomised to receive belimumab or placebo, 4 to 8 weeks following the first rituximab infusion. Belimumab or placebo infusions are administered for 52 weeks. The primary outcome measure is anti-double stranded DNA (anti-dsDNA) antibody levels at 52 weeks. Secondary outcomes include measures of adverse events, lupus disease activity and cumulative steroid dose. The kinetics of B cell repopulation will be assessed in a subgroup of participants. Belimumab administration after rituximab may provide a novel therapeutic pathway for patients with active lupus if safety is demonstrated in this proof of concept study, and lower anti-dsDNA antibodies levels are achieved in those patients treated with belimumab compared with placebo.Ethics and disseminationThe protocol has been reviewed and approved by the Hampstead Research Ethics Committee - London (reference 16/LO/1024). Trial information is available athttps://www.isrctn.com/ISRCTN47873003, and the results of this trial will be submitted for publication in relevant peer-reviewed journals. Key findings will also be presented at national and international conferences.Trial registration numberISRCTN47873; date assigned to the registry: 28 November 2016. The stage is pre-results.
Components of the full blood count as risk factors for colorectal cancer detection: a systematic review protocol
Authors: Virdee Pradeep S , Kirtley Shona , Elhussein Leena , Watkinson Peter J , Holt Tim A , Birks Jacqueline 
Published: December 2019

IntroductionColorectal cancer is the fourth most common type of cancer and the second most common cause of cancer-related deaths in the UK. The full blood count (FBC) is a blood test that may play a role in early detection of the disease. Previous studies have aimed to identify how levels of individual components, such as haemoglobin, can be used to assist the diagnosis. We aim to systematically review studies to identify whether components of the FBC are risk factors for diagnosis of colorectal cancer, critically appraise the methods used to assess the association and assess performance of the components.Methods and analysisThe MEDLINE (via OVID), EMBASE (via OVID), CINAHL (via EBSCOhost) and Web of Science databases will be searched to identify studies reporting the association between the levels of at least one FBC component and the risk of a future diagnosis of colorectal cancer in undiagnosed individuals. Clincialtrials.gov and the WHO registry will be searched to identify relevant ongoing research. Search terms will include relevant Medical Subject Headings and Emtree headings, and free-text terms relating to FBC, colorectal cancer and diagnosis. No date or language restrictions will be applied. Two reviewers will independently identify the studies for inclusion and perform data extraction. Time intervals between the blood tests and diagnosis will form the subgroups for analysis.Ethics and disseminationThere is no direct patient involvement and only published articles will be reviewed; no ethical approval is required. Results from this review will set a foundation for intended future work on developing a new risk score for early detection of colorectal cancer, derived using FBC data. This systematic review will also provide guidance on the analysis of time to diagnosis. The model will be freely available to UK primary care practices.PROSPERO registration numberCRD42019134400.
Improving accuracy of self-reported diagnoses of rheumatoid arthritis in the French prospective E3N-EPIC cohort: a validation study
Authors: Nguyen Yann , Salliot Carine , Gusto Gaëlle , Descamps Elise , Mariette Xavier , Boutron-Ruault Marie-Christine , Seror Raphaèle 
Published: December 2019

ObjectivesThe French E3N-EPIC (Etude Epidémiologique auprès des femmes de la Mutuelle générale de l’Education Nationale-European Prospective Investigation into Cancer and Nutrition) cohort enrolled 98 995 women aged 40 to 65 years at inclusion since 1990 to study the main risk factors for cancer and severe chronic conditions in women. They were prospectively followed with biennially self-administered questionnaires collecting self-reported medical, environmental and lifestyle data. Our objective was to assess the accuracy of self-reported diagnoses of rheumatoid arthritis (RA) and to devise algorithms to improve the ascertainment of RA cases in our cohort.DesignA validation study.ParticipantsWomen who self-reported an inflammatory rheumatic disease (IRD) were asked to provide access to their medical record, and to answer an IRD questionnaire. Medical records were independently reviewed.Primary and secondary outcome measuresPositive predictive values (PPV) of self-reported RA alone, then coupled with the IRD questionnaire, and with a medication reimbursement database were assessed. These algorithms were then applied to the whole cohort to ascertain RA cases.ResultsOf the 98 995 participants, 2692 self-reported RA. Medical records were available for a sample of 399 participants, including 305 who self-reported RA. Self-reported RA was accurate only for 42% participants. Combining self-reported diagnoses to answers to a specific IRD questionnaire or to the medication reimbursement database improved the PPV (75.6% and 90.1%, respectively). Using the devised algorithms, we could identify 964 RA cases in our cohort.ConclusionAccuracy of self-reported RA is poor but adding answers to a specific questionnaire or data from a medication reimbursement database performed satisfactorily to identify RA cases in our cohort. It will subsequently allow investigating many potential risk factors of RA in women.
Effects of rumen-protected methionine supplementation on growth performance, nitrogen balance, carcass characteristics, and meat quality of lambs fed diets containing buckwheat straw
Authors: Li Haiqing , Jiang Biwei , Zhou Yuxiang 
Published: December 2019

This study was conducted to determine the effects of rumen-protected methionine (RPM) supplementation on growth performance, nitrogen (N) balance, carcass traits, and meat quality of lambs fed diets containing buckwheat straw. Twenty male Tan lambs from Ningxia were housed in individual pens and were randomly assigned to five dietary treatments that were supplemented with RPM at levels of 0 (control), 1.5 (T1), 3.0 (T2), 4.5 (T3), and 6.0 g d−1 (T4). Dry matter intake was higher in T4 than control (P < 0.05). The feed:gain ratio generally reduced with increasing dietary RPM, but the lowest ratio was found in T3 (P < 0.05). Dry matter digestibility and N retention were highest in T3 (P < 0.05) while N excretion was the lowest. Carcass fat weight and grid reference tissue depth increased while drip loss decreased by supplemental RPM, and significant differences were found between T4 and control (P < 0.05). However, pH, color, cooking loss, and shear force were not affected. The results from this study demonstrated that dietary RPM supplementation may be able to improve the feed efficiency, N utilization, and meat quality of lambs; however, the optimal dose of RPM needs to be explored further.
Energy dependence of the efficiency of high-energy negatively charged particle beam deflection by planar channeling in a bent crystal
Authors: Kyryllin I. V. , Shul’ga N. F. 
Published: December 2019

AbstractThe study of planar channeling of high-energy negatively charged particles in bent crystals was carried out. The value of the critical radius of planar channeling in the Doyle–Turner approximation for the atomic potential is determined. The dependence of the maximum angle at which a given fraction of beam particles could be deflected by means of planar channeling in a bent crystal on the particle energy was found. We identified the ideal parameters for the exploitation of planar channeling for negatively charged particle beam deflection by planar channeling in a bent crystal at current and future high-energy accelerators, e.g., SLAC, MAMI, ILC or muon colliders.
Synthesis of NiO/TiO2 sub-microrods as catalyst for methanol oxidation reaction
Authors: Yue Xiaoyu , Wang Yixuan , Zhang Ting , Gao Wei 
Published: December 2019

[Formula: see text] sub-microrods have been synthesized via a simple two-step route. First, the precursors were prepared by a facile ethylene glycol-mediated method; then, [Formula: see text] sub-microrods were obtained by a limited-oxygen atmosphere deriving from the decomposition of urea at [Formula: see text]C for 3 h in air. The samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS) and transmission electron microscopy (TEM). The obtained [Formula: see text] sub-microrods exhibit cubic NiO structure with high crystallinity and anatase [Formula: see text]. Both SEM and TEM show the typical sub-microrods with lengths of [Formula: see text] nm and diameters of [Formula: see text] nm. The uniform sub-microrods have great electrocatalytic performance for methanol oxidation reaction in alkaline solution. This material may have potential applications in direct methanol fuel cells.
Tapir
Authors: Schardl Tao B. , Moses William S. , Leiserson Charles E. 
Published: December 2019

Tapir (pronounced TAY-per) is a compiler intermediate representation (IR) that embeds recursive fork-join parallelism, as supported by task-parallel programming platforms such as Cilk and OpenMP, into a mainstream compiler’s IR. Mainstream compilers typically treat parallel linguistic constructs as syntactic sugar for function calls into a parallel runtime. These calls prevent the compiler from performing optimizations on and across parallel control constructs. Remedying this situation has generally been thought to require an extensive reworking of compiler analyses and code transformations to handle parallel semantics. Tapir leverages the “serial-projection property,” which is commonly satisfied by task-parallel programs, to handle the semantics of these programs without an extensive rework of the compiler.
For recursive fork-join programs that satisfy the serial-projection property, Tapir enables effective compiler optimization of parallel programs with only minor changes to existing compiler analyses and code transformations. Tapir uses the serial-projection property to order logically parallel fine-grained tasks in the program’s control-flow graph. This ordered representation of parallel tasks allows the compiler to optimize parallel codes effectively with only minor modifications. For example, to implement Tapir/LLVM, a prototype of Tapir in the LLVM compiler, we added or modified less than 3,000 lines of LLVM’s half-million-line core middle-end functionality.
These changes sufficed to enable LLVM’s existing compiler optimizations for serial code—including loop-invariant-code motion, common-subexpression elimination, and tail-recursion elimination—to work with parallel control constructs such as parallel loops and Cilk’s Cilk_Spawn keyword. Tapir also supports parallel optimizations, such as loop scheduling, which restructure the parallel control flow of the program. By making use of existing LLVM optimizations and new parallel optimizations, Tapir/LLVM can optimize recursive fork-join programs more effectively than traditional compilation methods. On a suite of 35 Cilk application benchmarks, Tapir/LLVM produces more efficient executables for 30 benchmarks, with faster 18-core running times for 26 of them, compared to a nearly identical compiler that compiles parallel linguistic constructs the traditional way.
Checklist of beetles in the subgenus Copris (Paracopris) Balthasar from Asia with description of a new species, and redescription of Copris (Paracopris) punctulatus Wiedemann (Coleoptera: Scarabaeidae: Scarabaeinae)
Authors: BUI VAN BAC , ZIEGLER THOMAS , BONKOWSKI MICHAEL 
Published: December 2019

We present the first checklist of Asian beetles of the subgenus Copris (Paracopris) Balthasar, 1939 including new data on the distribution. In addition, Copris (Paracopris) javanensis Bui, Ziegler & Bonkowski, new species from Java (Indonesia) is described and Copris (Paracopris) punctulatus Wiedemann, 1823 is redescribed based on specimens deposited in the Muséum National d’Histoire Naturelle (Paris, France), including detailed illustrations of both sexes and male genitalia. At the same time, a neotype is designated for C. (P.) punctulatus as the type specimen was lost.
Costs and benefits of agricultural ammonia emission abatement options for compliance with European air quality regulations
Authors: Giannakis Elias , Kushta Jonilda , Bruggeman Adriana , Lelieveld Jos 
Published: December 2019

Abstract
Background
In Europe, ammonia (NH3) emissions strongly contribute to fine particulate matter (PM2.5) pollution and associated premature human mortality. The National Emission Ceilings Directive 2016/2284/EU has set an obligation for all European Union countries to reduce the NH3 emissions by 6%, relative to 2005, by 2020. This study aims to assess the costs and benefits of four NH3 emission abatement options for the compliance of the agricultural sector with the commitments of the European air quality regulatory framework. A regional atmospheric model (WRF/Chem) was used to assess the effects of regulating NH3 emissions reductions on PM2.5 concentrations over Europe. Non-market valuation techniques (value of statistical life) were used to monetize the associated health outcomes.

Results
We calculated that 16 out of the 28 EU member states exceeded their 2020 NH3 emission ceilings in 2016. The highest exceedances from the 2020 emission commitment level occurred in Latvia (15%), Germany (12%) and the UK (12%). Simulation of the required NH3 emission reduction by WRF/Chem showed that relatively large reductions in PM2.5 concentrations occur over central-western Europe and the UK. The largest health benefits (> 5% reduction in premature mortality) were found for Scandinavia. The economic benefit from avoided premature deaths over Europe amounts to 14,837 M€/year. The costs of four NH3 emission abatement options, where each would fully achieve the required emission reduction, range from 80 M€/year for low nitrogen feed to 3738 M€/year for low-emission animal housing, with covered manure storage (236 M€/year) and urea fertilizer application (253 M€/year), in between.

Conclusion
Our analysis indicates that the costs of compliance by the agricultural sector with the commitments of the European air quality regulations are much lower than the economic benefit. Thus, much more ambitious reduction commitments for NH3 emissions could be applied by the EU-28. The monetization of the health benefits of NH3 emission abatement policies and the assessment of the implementation costs can help policy-makers devise effective air pollution control programmes.
Distinguishing successive ancient polyploidy levels based on genome-internal syntenic alignment
Authors: Zhang Yue , Zheng Chunfang , Sankoff David 
Published: December 2019

AbstractBackgroundA basic tool for studying the polyploidization history of a genome, especially in plants, is the distribution of duplicate gene similarities in syntenically aligned regions of a genome. This distribution can usually be decomposed into two or more components identifiable by peaks, or local maxima, each representing a different polyploidization event. The distributions may be generated by means of a discrete time branching process, followed by a sequence divergence model. The branching process, as well as the inference of fractionation rates based on it, requires knowledge of the ploidy level of each event, which cannot be directly inferred from the pair similarity distribution.ResultsFor a sequence of two events of unknown ploidy, either tetraploid, giving rise to whole genome doubling (WGD), or hexaploid, giving rise to whole genome tripling (WGT), we base our analysis on triples of similar genes. We calculate the probability of the four triplet types with origins in one or the other event, or both, and impose a mutational model so that the distribution resembles the original data. Using a ML transition point in the similarities between the two events as a discriminator for the hypothesized origin of each similarity, we calculate the predicted number of triplets of each type for each model combining WGT and/or WGD. This yields a predicted profile of triplet types for each model. We compare the observed and predicted triplet profiles for each model to confirm the polyploidization history of durian, poplar and cabbage.ConclusionsWe have developed a way of inferring the ploidy of up to three successive WGD and/or WGT events by estimating the time of origin of each of the similarities in triples of genes. This may be generalized to a larger number of events and to higher ploidies.
Generating normal networks via leaf insertion and nearest neighbor interchange
Authors: Zhang Louxin 
Published: December 2019

Abstract
Background
Galled trees are studied as a recombination model in theoretical population genetics. This class of phylogenetic networks has been generalized to tree-child networks and other network classes by relaxing a structural condition imposed on galled trees. Although these networks are simple, their topological structures have yet to be fully understood.

Results
It is well-known that all phylogenetic trees on n taxa can be generated by the insertion of the n-th taxa to each edge of all the phylogenetic trees on n−1 taxa. We prove that all tree-child (resp. normal) networks with k reticulate nodes on n taxa can be uniquely generated via three operations from all the tree-child (resp. normal) networks with k−1 or k reticulate nodes on n−1 taxa. Applying this result to counting rooted phylogenetic networks, we show that there are exactly $\frac {(2n)!}{2^{n} (n-1)!}-2^{n-1} n!$(2n)!2n(n−1)!−2n−1n! binary phylogenetic networks with one reticulate node on n taxa.

Conclusions
The work makes two contributions to understand normal networks. One is a generalization of an enumeration procedure for phylogenetic trees into one for normal networks. Another is simple formulas for counting normal networks and phylogenetic networks that have only one reticulate node.
Modeling aspects of the language of life through transfer-learning protein sequences
Authors: Heinzinger Michael , Elnaggar Ahmed , Wang Yu , Dallago Christian , Nechaev Dmitrii , Matthes Florian , Rost Burkhard 
Published: December 2019

AbstractBackgroundPredicting protein function and structure from sequence is one important challenge for computational biology. For 26 years, most state-of-the-art approaches combined machine learning and evolutionary information. However, for some applications retrieving related proteins is becoming too time-consuming. Additionally, evolutionary information is less powerful for small families, e.g. for proteins from theDark Proteome. Both these problems are addressed by the new methodology introduced here.ResultsWe introduced a novel way to represent protein sequences as continuous vectors (embeddings) by using the language model ELMo taken from natural language processing. By modeling protein sequences, ELMo effectively captured the biophysical properties of the language of life from unlabeled big data (UniRef50). We refer to these new embeddings asSeqVec(Sequence-to-Vector) and demonstrate their effectiveness by training simple neural networks for two different tasks. At the per-residue level, secondary structure (Q3 = 79% ± 1, Q8 = 68% ± 1) and regions with intrinsic disorder (MCC = 0.59 ± 0.03) were predicted significantly better than through one-hot encoding or through Word2vec-like approaches. At the per-protein level, subcellular localization was predicted in ten classes (Q10 = 68% ± 1) and membrane-bound were distinguished from water-soluble proteins (Q2 = 87% ± 1). AlthoughSeqVecembeddings generated the best predictions from single sequences, no solution improved over the best existing method using evolutionary information. Nevertheless, our approach improved over some popular methods using evolutionary information and for some proteins even did beat the best. Thus, they prove to condense the underlying principles of protein sequences. Overall, the important novelty is speed: where the lightning-fastHHblitsneeded on average about two minutes to generate the evolutionary information for a target protein,SeqVeccreated embeddings on average in 0.03 s. As this speed-up is independent of the size of growing sequence databases,SeqVecprovides a highly scalable approach for the analysis of big data in proteomics, i.e. microbiome or metaproteome analysis.ConclusionTransfer-learning succeeded to extract information from unlabeled sequence databases relevant for various protein prediction tasks. SeqVec modeled the language of life, namely the principles underlying protein sequences better than any features suggested by textbooks and prediction methods. The exception is evolutionary information, however, that information is not available on the level of a single sequence.