bluuebunny/crossref_metadata_2025_split huggingface dataset:
Keepingcrisprin check: diverse mechanisms of phage-encoded anti-crisprs
Authors: Trasanidou Despoina , Gerós Ana Sousa , Mohanraju Prarthana , Nieuwenweg Anna Cornelia , Nobrega Franklin L , Staals Raymond H J 
Published: May 2019

ABSTRACTCRISPR-Cas represents the only adaptive immune system of prokaryotes known to date. These immune systems are widespread among bacteria and archaea, and provide protection against invasion of mobile genetic elements, such as bacteriophages and plasmids. As a result of the arms-race between phages and their prokaryotic hosts, phages have evolved inhibitors known as anti-CRISPR (Acr) proteins to evade CRISPR immunity. In the recent years, several Acr proteins have been described in both temperate and virulent phages targeting diverse CRISPR-Cas systems. Here, we describe the strategies of Acr discovery and the multiple molecular mechanisms by which these proteins operate to inhibit CRISPR immunity. We discuss the biological relevance of Acr proteins and speculate on the implications of their activity for the development of improved CRISPR-based research and biotechnological tools.
Hepatitis D infection: from initial discovery to current investigational therapies
Authors: Da Ben L , Heller Theo , Koh Christopher 
Published: May 2019

AbstractHepatitis D is the most severe form of viral hepatitis associated with a more rapid progression to cirrhosis and an increased risk of hepatocellular carcinoma and mortality compared with hepatitis B mono-infection. Although once thought of as a disappearing disease, hepatitis D is now becoming recognized as a serious worldwide issue due to improvement in diagnostic testing and immigration from endemic countries. Despite these concerns, there is currently only one accepted medical therapy (pegylated-interferon-α) for the treatment of hepatitis D with less than desirable efficacy and significant side effects. Due to these reasons, many patients never undergo treatment. However, increasing knowledge about the virus and its life cycle has led to the clinical development of multiple promising new therapies that hope to alter the natural history of this disease and improve patient outcome. In this article, we will review the literature from discovery to the current investigational therapies.
A comparison of text versus audio for information comprehension with future uses for smart speakers
Authors: Leroy Gondy , Kauchak David 
Published: May 2019

Abstract

Objective
Audio is increasingly used to access information on the Internet through virtual assistants and smart speakers. Our objective is to evaluate the distribution of health information through audio.

Materials and Methods
We conducted 2 studies to compare comprehension after reading or listening to information using a new corpus containing short text snippets from Cochrane (N = 50) and Wikipedia (N = 50). In study 1, the snippets were first presented as audio or text followed by a multiple-choice question. Then, the same information was presented as text and the question was repeated in addition to questions about perceived difficulty, severity and the likelihood of encountering the disease. In study 2, the first multiple-choice question was replaced with a free recall question.

Results
Study 1 showed that information comprehension is very similar in both presentation modes (53% accuracy for text and 55% for audio). Study 2 showed that information retention is higher with text, but similar comprehension. Both studies show improvement in performance with repeated information presentation.

Discussion
Audio presentation of information is effective and the format novel. Performance was slightly lower with audio when asked to repeat information, but comparable to text for answering questions. Additional studies are needed with different types of information and presentation combinations.

Conclusion
The use of audio to provide health information is a promising field and will become increasingly important with the popularity of smart speakers and virtual assistants, particularly for consumers who do not use computers, for example minority groups, or those with limited sight or motor control.
Available energy and amino acid digestibility of yellow dent corn fed to growing pigs1
Authors: Lyu Zhiqian , Li Quanfeng , Zhang Shuai , Lai Changhua , Huang Chengfei 
Published: May 2019

AbstractTwo experiments were conducted to determine the DE and ME as well as the apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of CP and AA in corn fed to growing pigs. All corn was yellow dent corn collected from different areas in China. In Exp. 1, 60 crossbred barrows (Duroc × Landrace × Yorkshire; 40.7 ± 3.5 kg BW) were randomly allotted to 1 of 10 diets to determine the DE and ME of corns. Diets were formulated to contain 96.8% of 1 of the 10 corn samples and 3.2% of other microingredients. In Exp. 2, 11 crossbred barrows (Duroc × Landrace × Yorkshire; 30.5 ± 2.3 kg) fitted with a T-cannula at the distal ileum were assigned to a 6 × 11 Youden square design with 6 periods and 11 diets. Diets included a N-free diet based on cornstarch and sucrose and 10 test diets formulated with 96.6% 1 of the 10 corns as the sole source of AA. Chromic oxide (0.3%) was added to each diet as an indigestible marker for calculating the AA digestibility. On a DM basis, the starch, ether extract (EE), CP, NDF, and ADF contents of corns averaged 74.05% (69.98 to 78.59%), 3.83% (2.04 to 4.73%), 9.63% (7.74 to 10.43%), 10.80% (10.27 to 11.46%), and 2.27% (2.03 to 2.57%), respectively. The CV of EE, CP, and ADF was 22.59, 8.22, and 8.21%, respectively. The DE and ME of corns averaged 4,087 and 3,981 kcal/kg, respectively, and ranged from 3,999 to 4,161 kcal/kg and from 3,898 to 4,067 kcal/kg, respectively. The DE and ME values were positively correlated (P < 0.05) with the EE content. Optimal prediction equations of ME were ME = 940.35 + (0.72 × DE) + (21.88 × EE) (R2 = 0.94) or ME = 1,051.50 + (0.82 × DE) − (282.05 × ash) (R2 = 0.99). In Exp. 2, significant differences (P < 0.05) were observed in the SID of Arg, His, Phe, Ala, Pro, Cys, and Tyr. The SID of Lys (average 73.79%), Met (average 87.32%), and Thr (average 80.06%) ranged from 61.45 to 78.47%, from 74.09 to 90.91%, and from 79.19 to 85.79%, respectively. The standardized ileal digestible Met was positively correlated (P < 0.01) with the Met and CP contents. The obtained prediction equations were standardized ileal digestible Met = 31.34 + (3.43 × CP) + (116.04 × Met) and standardized ileal digestible Met = 104.92 + (294.71 × Met) − (7.03 × NDF). In conclusion, sources had an effect on the energy values and ileal digestibility of most AA in corn. The ME can be predicted by the DE combined with either the EE or ash content. The AA concentrations and SID of AA in corn varied largely.
Genome-Wide Single Nucleotide Polymorphisms are Robust in Resolving Fine-Scale Population Genetic Structure of the Small Brown Planthopper, Laodelphax striatellus (Fallén) (Hemiptera: Delphacidae)
Authors: Liu Yan , Chen Lei , Duan Xing-Zhi , Zhao Dian-Shu , Sun Jing-Tao , Hong Xiao-Yue 
Published: May 2019

Abstract
Deciphering genetic structure and inferring migration routes of insects with high migratory ability have been challenging, due to weak genetic differentiation and limited resolution offered by traditional genotyping methods. Here, we tested the ability of double digest restriction-site associated DNA sequencing (ddRADseq)-based single nucleotide polymorphisms (SNPs) in revealing the population structure relative to 13 microsatellite markers by using four small brown planthopper populations as subjects. Using ddRADseq, we identified 230,000 RAD loci and 5,535 SNP sites, which were present in at least 80% of individuals across the four populations with a minimum sequencing depth of 10. Our results show that this large SNP panel is more powerful than traditional microsatellite markers in revealing fine-scale population structure among the small brown planthopper populations. In contrast to the mixed population structure suggested by microsatellites, discriminant analysis of principal components (DAPC) of the SNP dataset clearly separated the individuals into four geographic populations. Our results also suggest the DAPC analysis is more powerful than the principal component analysis (PCA) in resolving population genetic structure of high migratory taxa, probably due to the advantages of DAPC in using more genetic variation and the discriminant analysis function. Together, these results point to ddRADseq being a promising approach for population genetic and migration studies of small brown planthopper.
The road map of cancer precision medicine with the innovation of advanced cancer detection technology and personalized immunotherapy
Authors: Low Siew-Kee , Nakamura Yusuke 
Published: May 2019

Abstract
The advancement of cancer genomics research due to the development of next generation sequencing technologies is going to bring the promise of cancer precision medicine, in turn revolutionizing cancer detection and treatment. In this review, we will discuss the possible road map for implementation of cancer precision medicine into the clinical practice by mainly focusing on the role of liquid biopsy, particularly circulating tumor DNA, as a potential tool for cancer screening, selection of an appropriate drug(s), surveillance of minimal residual diseases, and early detection of recurrence. We will also review the current status of genome-driven oncology and emerging field of immunotherapies that could be provided to patients to improve their clinical outcome and quality of life. Lastly, we will discuss the usefulness of artificial intelligence that facilitate complex data integration in our health care/medical care system.
Data quality and the comparative method: the case of pregnancy failure in rodents
Authors: Stokes Rachel H , Sandel Aaron A 
Published: May 2019

Abstract
In mammalian species where infanticide by males is likely, females exhibit counterstrategies to prevent or mitigate the costs of infanticide. One putative mitigation strategy is the “Bruce effect,” in which pregnant or inseminated females exposed to an unfamiliar male experience pregnancy block or failure. Females then mate with the new male, thus shifting investment from a “doomed” pregnancy to a more fruitful one. However, the Bruce effect may be an adaptive response to other factors besides infanticide. For example, if paternal care is necessary for offspring survival, and an unfamiliar male replacing the original mate is unlikely to provide such care to offspring of a litter it did not sire, then a female may terminate a pregnancy to initiate a new one. The infanticide and paternal care hypotheses have not been rigorously tested because comparative data on the Bruce effect across mammals are scarce. We compiled data on the Bruce effect, infanticide, and paternal care from one particularly rich source of information, rodents, but found the data set to be less rich than expected. The Bruce effect, infanticide, and paternal care were common among rodent species, but we found no clear relationship among the traits. However, this was likely due to 1) a bias toward positive results, 2) missing data, and 3) a reliance on studies of captive animals. These are common problems in comparative research, and we outline standards that should be implemented to successfully answer questions of importance in the field.
Radio jet structures at ∼100 pc and larger scales of the γ-ray-emitting narrow-line Seyfert 1 galaxy PMN J0948+0022
Authors: Doi Akihiro , Nakahara Satomi , Nakamura Masanori , Kino Motoki , Kawakatu Nozomu , Nagai Hiroshi 
Published: May 2019

Abstract
The narrow-line Seyfert 1 (NLS1) galaxy PMN J0948+0022 is an archetype of γ-ray-emitting NLS1s in active galactic nuclei (AGNs). In this study, we investigate its radio structures using archival data obtained using the Karl G. Jansky Very Large Array (VLA) and the Very Long Baseline Array (VLBA). The new VLA images reveal an outermost radio emission separated by 9.1 arcsec. Its resolved structure and steep spectrum suggest a terminal shock in a radio lobe energized by the jet from the PMN J0948+0022 nucleus. This large-scale radio component is found at almost the same position angle as that of the pc-scale jet, indicating a stable jet direction up to ∼1 Mpc. Its apparent one-sidedness implies a moderate advancing speed (β &gt; 0.27). The kinematic age of &lt;1× 107 yr of the jet activity is consistent with the expected NLS1 phase of ∼107 yr in the AGN lifetime. The VLBA image reveals the jet structure at distances ranging from r = 0.82 milliarcsec to 3.5 milliarcsec, corresponding to approximately 100 pc, where superluminal motions were found. The jet width profile (∝ r1.12) and flux-density profile (∝ r−1.44) depending on the distance r along the jet suggest that the jet kinetic energy is converted to internal energy in this region. The jet is causally connected in a nearly conical streamline, which is supported by ambient pressure at 100 pc scales in the host galaxy of PMN J0948+0022.
Discovery of millihertz quasi-periodic oscillations in the X-ray binary EXO 0748−676
Authors: Mancuso G C , Altamirano D , García F , Lyu M , Méndez M , Combi J A , Díaz-Trigo M , in’t Zand J J M 
Published: May 2019

Abstract
We report the discovery of millihertz quasi-periodic oscillations (mHz QPOs) from the bursting, high-inclination atoll neutron star low-mass X-ray binary (NS LMXB) EXO 0748−676 with the Rossi X-ray Time Explorer (RXTE). This class of QPO, originally discovered in three NS LMXBs, has been interpreted as a consequence of a special mode of nuclear burning on the NS surface. Using all the RXTE archival observations of the source, we detected significant (&gt;3σ) mHz QPOs in 11 observations. The frequency of the oscillations was between ∼5 and ∼13 mHz. We also found a decrease of the QPO frequency with time in two occasions; in one of these the oscillations disappeared with the onset of an X-ray burst, similar to what was reported in other sources. Our analysis of the X-ray colours revealed that EXO 0748−676 was in a soft spectral state when it exhibited the QPOs. This makes EXO 0748−676 the sixth source with mHz oscillations associated with marginally stable burning, and the second one that shows a systematic frequency drift. Our results suggest that the mechanism that produces the drift might always be present if the mHz QPOs are observed in the so-called intermediate state.
Candidates for RR Lyrae in binary systems from the OGLE Galactic bulge survey
Authors: Prudil Z , Skarka M , Liška J , Grebel E K , Lee C-U 
Published: May 2019

ABSTRACT
We present 20 newly discovered candidates for binary systems with an RR Lyrae companion. Using the photometric data from the Optical Gravitational Lensing Experiment (OGLE) and Korea Microlensing Telescope Network (KMTNet) for the Galactic bulge, we searched for binary candidates among non-modulated fundamental-mode RR Lyrae variables. We constructed and investigated over 9000 O − C diagrams for individual pulsators, in order to find signs of the light-travel time effect. We found 20 variables exhibiting cyclic variation in the O − C (time of the observed minus calculated brightness maximum) diagram, which can be associated with a second component in the system, but for confirmation of binarity, a long-term radial velocity study is necessary. The modelling of the O − C diagrams yields orbital parameters, estimates of the semi-amplitude of the radial velocity curve, and the mass function. The orbital periods of our candidates range from 3 to 15 yr. Two of the binary candidates display a minimum mass higher than the assumed mass of the RR Lyrae component, which points towards an evolved companion that can under some circumstances contribute significantly to the total light of the system.
Trehalase Gene as a Molecular Signature of Dietary Diversification in Mammals
Authors: Jiao Hengwu , Zhang Libiao , Xie Huan-Wang , Simmons Nancy B , Liu Hui , Zhao Huabin 
Published: May 2019

AbstractDiet is a key factor in determining and structuring animal diversity and adaptive radiations. The mammalian fossil record preserves phenotypic evidence of many dietary shifts, whereas genetic changes followed by dietary diversification in mammals remain largely unknown. To test whether living mammals preserve molecular evidence of dietary shifts, we examined the trehalase gene (Treh), which encodes an enzyme capable of digesting trehalose from insect blood, in bats and other mammals with diverse diets. Bats represent the largest dietary radiation among all mammalian orders, with independent origins of frugivory, nectarivory, carnivory, omnivory, and even sanguivory in an otherwise insectivorous clade. We found that Treh has been inactivated in unrelated bat lineages that independently radiated into noninsectivorous niches. Consistently, purifying selection has been markedly relaxed in noninsectivorous bats compared with their insectivorous relatives. Enzymatic assays of intestinal trehalase in bats suggest that trehalase activity tends to be lost or markedly reduced in noninsectivorous bats compared with their insectivorous relatives. Furthermore, our survey of Treh in 119 mammal species, which represent a deeper evolutionary timeframe, additionally identified a number of other independent losses of Treh in noninsectivorous species, recapitulating the evolutionary pattern that we found in bats. These results document a molecular record of dietary diversification in mammals, and suggest that such molecular signatures of dietary shifts would help us understand both historical and modern changes of animal diets.
GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis
Authors: Tang Zefang , Kang Boxi , Li Chenwei , Chen Tianxiang , Zhang Zemin 
Published: May 2019

Abstract
Introduced in 2017, the GEPIA (Gene Expression Profiling Interactive Analysis) web server has been a valuable and highly cited resource for gene expression analysis based on tumor and normal samples from the TCGA and the GTEx databases. Here, we present GEPIA2, an updated and enhanced version to provide insights with higher resolution and more functionalities. Featuring 198 619 isoforms and 84 cancer subtypes, GEPIA2 has extended gene expression quantification from the gene level to the transcript level, and supports analysis of a specific cancer subtype, and comparison between subtypes. In addition, GEPIA2 has adopted new analysis techniques of gene signature quantification inspired by single-cell sequencing studies, and provides customized analysis where users can upload their own RNA-seq data and compare them with TCGA and GTEx samples. We also offer an API for batch process and easy retrieval of the analysis results. The updated web server is publicly accessible at http://gepia2.cancer-pku.cn/.
The structure of human EXD2 reveals a chimeric 3′ to 5′ exonuclease domain that discriminates substrates via metal coordination
Authors: Park Jumi , Lee Song-Yi , Jeong Hanbin , Kang Myeong-Gyun , Van Haute Lindsey , Minczuk Michal , Seo Jeong Kon , Jun Youngsoo , Myung Kyungjae , Rhee Hyun-Woo , Lee Changwook 
Published: May 2019

Abstract
EXD2 (3′-5′ exonuclease domain-containing protein 2) is an essential protein with a conserved DEDDy superfamily 3′-5′ exonuclease domain. Recent research suggests that EXD2 has two potential functions: as a component of the DNA double-strand break repair machinery and as a ribonuclease for the regulation of mitochondrial translation. Herein, electron microscope imaging analysis and proximity labeling revealed that EXD2 is anchored to the mitochondrial outer membrane through a conserved N-terminal transmembrane domain, while the C-terminal region is cytosolic. Crystal structures of the exonuclease domain in complex with Mn2+/Mg2+ revealed a domain-swapped dimer in which the central α5−α7 helices are mutually crossed over, resulting in chimeric active sites. Additionally, the C-terminal segments absent in other DnaQ family exonucleases enclose the central chimeric active sites. Combined structural and biochemical analyses demonstrated that the unusual dimeric organization stabilizes the active site, facilitates discrimination between DNA and RNA substrates based on divalent cation coordination and generates a positively charged groove that binds substrates.
Photopenic defects on O-(2-[18F]-fluoroethyl)-L-tyrosine PET: clinical relevance in glioma patients
Authors: Galldiks Norbert , Unterrainer Marcus , Judov Natalie , Stoffels Gabriele , Rapp Marion , Lohmann Philipp , Vettermann Franziska , Dunkl Veronika , Suchorska Bogdana , Tonn Jörg C , Kreth Friedrich-Wilhem , Fink Gereon R , Bartenstein Peter , Langen Karl-Josef , Albert Nathalie L 
Published: May 2019

Abstract

Background
O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET has a sensitivity of more than 90% to detect gliomas. In the remaining small fraction of gliomas without increased tracer uptake, some tumors even show photopenic defects whose clinical significance is unclear.

Methods
Glioma patients with a negative FET PET scan prior to neuropathological confirmation were identified retrospectively. Gliomas were rated visually as (i) having indifferent FET uptake or (ii) photopenic, if FET uptake was below background activity. FET uptake in the area of signal hyperintensity on the T2/fluid attenuated inversion recovery–weighted MRI was evaluated by mean standardized uptake value (SUV) and mean tumor-to-brain ratio (TBR). The progression-free survival (PFS) of photopenic gliomas was compared with that of gliomas with indifferent FET uptake.

Results
Of 100 FET-negative gliomas, 40 cases with photopenic defects were identified. Fifteen of these 40 cases (38%) had World Health Organization (WHO) grades III and IV gliomas. FET uptake in photopenic gliomas was significantly decreased compared with both the healthy-appearing brain tissue (SUV, 0.89 ± 0.26 vs 1.08 ± 0.23; P < 0.001) and gliomas with indifferent FET uptake (TBR, 0.82 ± 0.09 vs 0.96 ± 0.13; P < 0.001). Irrespective of the applied treatment, isocitrate dehydrogenase (IDH)–mutated WHO grade II diffuse astrocytoma patients with indifferent FET uptake (n = 25) had a significantly longer PFS than patients with IDH-mutated diffuse astrocytomas (WHO grade II) with photopenic defects (n = 11) (51 vs 24 mo; P = 0.027). The multivariate survival analysis indicated that photopenic defects predict an unfavorable PFS (P = 0.009).

Conclusion
Photopenic gliomas in negative FET PET scans should be managed more actively, as they seem to have a higher risk of harboring a higher-grade glioma and an unfavorable outcome.