bluuebunny/crossref_metadata_2025_split huggingface dataset:
Terminating contamination: large-scale search identifies more than 2,000,000 contaminated entries in GenBank
Authors: Steinegger Martin , Salzberg Steven L. 
Published: May 2020

AbstractGenomic analyses are sensitive to contamination in public databases caused by incorrectly labeled reference sequences. Here, we describe Conterminator, an efficient method to detect and remove incorrectly labeled sequences by an exhaustive all-against-all sequence comparison. Our analysis reports contamination of 2,161,746, 114,035, and 14,148 sequences in the RefSeq, GenBank, and NR databases, respectively, spanning the whole range from draft to “complete” model organism genomes. Our method scales linearly with input size and can process 3.3 TB in 12 days on a 32-core computer. Conterminator can help ensure the quality of reference databases. Source code (GPLv3):https://github.com/martin-steinegger/conterminator
An antibiotic stewardship programme to reduce inappropriate antibiotic prescribing for acute respiratory infections in rural Chinese primary care facilities: study protocol for a clustered randomised controlled trial
Authors: Zhuo Chao , Wei Xiaolin , Zhang Zhitong , Hicks Joseph Paul , Zheng Jinkun , Chen Zhixu , Haldane Victoria , Walley John , Guan Yubao , Xu Hongyan , Zhong Nanshan 
Published: May 2020

Abstract
Background
Inappropriate prescribing of antibiotics for acute respiratory infections at the primary care level represents the major source of antibiotic misuse in healthcare, and is a major driver for antimicrobial resistance worldwide. In this study we will develop, pilot and evaluate the effectiveness of a comprehensive antibiotic stewardship programme in China’s primary care hospitals to reduce inappropriate prescribing of antibiotics for acute respiratory infections among all ages.

Methods
We will use a parallel-group, cluster-randomised, controlled, superiority trial with blinded outcome evaluation but unblinded treatment (providers and patients). We will randomise 34 primary care hospitals from two counties within Guangdong province into the intervention and control arm (1:1 overall ratio) stratified by county (8:9 within-county ratio). In the control arm, antibiotic prescribing and management will continue through usual care. In the intervention arm, we will implement an antibiotic stewardship programme targeting family physicians and patients/caregivers. The family physician components include: (1) training using new operational guidelines, (2) improved management and peer-review of antibiotic prescribing, (3) improved electronic medical records and smart phone app facilitation. The patient/caregiver component involves patient education via family physicians, leaflets and videos. The primary outcome is the proportion of prescriptions for acute respiratory infections (excluding pneumonia) that contain any antibiotic(s). Secondary outcomes will address how frequently specific classes of antibiotics are prescribed, how frequently key non-antibiotic alternatives are prescribed and the costs of consultations. We will conduct a qualitative process evaluation to explore operational questions regarding acceptability, cultural appropriateness and burden of technology use, as well as a cost-effectiveness analysis and a long-term benefit evaluation. The duration of the intervention will be 12 months, with another 24 months’ post-trial long-term follow-up.

Discussion
Our study is one of the first trials to evaluate the effect of an antibiotic stewardship programme in primary care settings in a low- or middle-income country (LMIC). All interventional activities will be designed to be embedded into routine primary care with strong local ownership. Through the trial we intend to impact on clinical practice and national policy in antibiotic prescription for primary care facilities in rural China and other LMICs.

Trial registration
ISRCTN, ID: ISRCTN96892547. Registered on 18 August 2019.
Transgenerational epigenetic effects from male exposure to endocrine-disrupting compounds: a systematic review on research in mammals
Authors: Van Cauwenbergh Olivia , Di Serafino Alessandra , Tytgat Jan , Soubry Adelheid 
Published: May 2020

AbstractAssessing long-term health effects from a potentially harmful environment is challenging. Endocrine-disrupting compounds (EDCs) have become omnipresent in our environment. Individuals may or may not experience clinical health issues from being exposed to the increasing environmental pollution in daily life, but an issue of high concern is that also the non-exposed progeny may encounter consequences of these ancestral exposures. Progress in understanding epigenetic mechanisms opens new perspectives to estimate the risk of man-made EDCs. However, the field of epigenetic toxicology is new and its application in public health or in the understanding of disease etiology is almost non-existent, especially if it concerns future generations. In this review, we investigate the literature on transgenerational inheritance of diseases, published in the past 10 years. We question whether persistent epigenetic changes occur in the male germ line after exposure to synthesized EDCs. Our systematic search led to an inclusion of 43 articles, exploring the effects of commonly used synthetic EDCs, such as plasticizers (phthalates and bisphenol A), pesticides (dichlorodiphenyltrichloroethane, atrazine, vinclozin, methoxychlor), dioxins, and polycyclic aromatic hydrocarbons (PAHs, such as benzo(a)pyrene). Most studies found transgenerational epigenetic effects, often linked to puberty- or adult-onset diseases, such as testicular or prostate abnormalities, metabolic disorders, behavioral anomalies, and tumor development. The affected epigenetic mechanisms included changes in DNA methylation patterns, transcriptome, and expression of DNA methyltransferases. Studies involved experiments in animal models and none were based on human data. In the future, human studies are needed to confirm animal findings. If not transgenerational, at least intergenerational human studies and studies on EDC-induced epigenetic effects on germ cells could help to understand early processes of inheritance. Next, toxicity tests of new chemicals need a more comprehensive approach before they are introduced on the market. We further point to the relevance of epigenetic toxicity tests in regard to public health of the current population but also of future generations. Finally, this review sheds a light on how the interplay of genetics and epigenetics may explain the current knowledge gap on transgenerational inheritance.
Promoter methylation changes in ALOX12 and AIRE1: novel epigenetic markers for atherosclerosis
Authors: Kim Jee Yeon , Choi Bong-Geun , Jelinek Jaroslav , Kim Dae Hyun , Lee Seo Hyun , Cho Kwangjo , Rha Seo Hee , Lee Young Ho , Jin Hyo Sun , Choi Dae-Kyoung , Kim Geun-Eun , Kwon Sun U. , Hwang Junha , Cha Jae Kwan , Lee Sukhoon , Issa Jean-Pierre J. , Kim Jei 
Published: May 2020

Abstract
Background
Atherosclerosis is the main cause of cardiovascular diseases such as ischemic stroke and coronary heart disease. Gene-specific promoter methylation changes have been suggested as one of the causes underlying the development of atherosclerosis. We aimed to identify and validate specific genes that are differentially expressed through promoter methylation in atherosclerotic plaques. We performed the present study in four steps: (1) profiling and identification of gene-specific promoter methylation changes in atherosclerotic tissues; (2) validation of the promoter methylation changes of genes in plaques by comparison with non-plaque intima; (3) evaluation of promoter methylation status of the genes in vascular cellular components composing atherosclerotic plaques; and (4) evaluation of promoter methylation differences in genes among monocytes, T cells, and B cells isolated from the blood of ischemic stroke patients.

Results
Upon profiling, AIRE1, ALOX12, FANK1, NETO1, and SERHL2 were found to have displayed changes in promoter methylation. Of these, AIRE1 and ALOX12 displayed higher methylation levels in plaques than in non-plaque intima, but lower than those in the buffy coat of blood. Between inflammatory cells, the three genes were significantly less methylated in monocytes than in T and B cells. In the vascular cells, AIRE1 methylation was lower in endothelial and smooth muscle cells. ALOX12 methylation was higher in endothelial, but lower in smooth muscle cells. Immunofluorescence staining showed that co-localization of ALOX12 and AIRE1 was more frequent in CD14(+)-monocytes than in CD4(+)-T cell in plaque than in non-plaque intima.

Conclusions
Promoter methylation changes in AIRE1 and ALOX12 occur in atherosclerosis and can be considered as novel epigenetic markers.
Exploration of the safe water content and activity control points for medicinal and edible lotus seeds from mildew
Authors: Liao Xiaofang , Sun Chaonan , Wei Fang , Zhou Lidong , Kong Weijun 
Published: May 2020

AbstractAffected by the inner properties and the external environmental conditions, medicinal and edible lotus seeds are susceptible to mildew with fungal infection under suitable temperature and humidity conditions, leading to the production and contamination of various mycotoxins, along with threats to its quality and safety. In this study, the changes of water content (Cw) and water activity (Aw) of lotus seeds stored at 25 °C and different relative humidity conditions, as well as the correlation between them and mildew of this edible and medicinal material were studied, aiming to explore the safe Cw and Aw control points for screening out the suitable storage conditions from mildew. Blank (without fungal conidia) and experimental (artificially added with Aspergillus flavus conidia) groups of lotus seeds were stored at 25 °C and relative humidity of 40%, 50%, 60% and 70% for about 30 days, respectively. The mildew was observed and the changes of Cw, Aw, together with the production of aflatoxins were measured. Results showed that no mildew was found and aflatoxins were not detected in lotus seeds when they were stored for 30 days at 25 °C and relative humidity of 40%, 50% and 60% with Cw < 12% and Aw < 0.6. While, when the relative humidity was up to 70%, the Cw and Aw values rose quickly, and the Cw exceeded the officially-permitted level (14%). Although no mildew was observed, AFB1 was still detected, increasing the potential risk of lotus seeds regarding aflatoxins. For warranting the quality with economic and safe storage, lotus seeds are suggested to be stored at 25 °C and relative humidity lower than 60% with 12% and 0.6 as the safe Cw and Aw control points, respectively, to prevent medicinal and edible products from mildew and the contamination of aflatoxins.
Logistic regression based in-service assessment of mobile web browsing service quality acceptability
Authors: Isak-Zatega Sibila , Lipovac Adriana , Lipovac Vlatko 
Published: May 2020

AbstractIn this paper, we presented a logistic regression model that we applied for assessment of the users’ quality of experience with web browsing service over mobile network. With this regard, we chose the Average-Time-to-Connect-TCP network service quality parameter as an independent predictor, obtained by passive monitoring of live traffic data, captured by a passive probe on the mobile network Gn interface, and related to detailed records of the Transport Control Protocol. In parallel with in-service measuring the selected network parameter, we conducted simultaneous subjective tests of the quality of experience acceptability to users, specifically for web browsing service. Particularly, it was found that the model provided correct acceptability classification in 84.5% of cases, while reducing the chosen independent predictor for 100 ms implied increasing the chance of the service acceptability by factor of 1.65. Based on the obtained results, it comes out that the applied logistic regression model provides satisfactory estimation of the web browsing service quality experience acceptability.
Persistent elevation of intrathecal pro-inflammatory cytokines leads to multiple sclerosis-like cortical demyelination and neurodegeneration
Authors: James Rachel E. , Schalks Renee , Browne Eleanor , Eleftheriadou Ioanna , Munoz Carmen Picon , Mazarakis Nicholas D. , Reynolds Richard 
Published: May 2020

AbstractAnalysis of isolated meninges and cerebrospinal fluid (CSF) of post-mortem MS cases has shown increased gene and protein expression for the pro-inflammatory cytokines: tumour necrosis factor (TNF) and interferon-γ (IFNγ). Here we tested the hypothesis that persistent production of these cytokines in the meningeal compartment and diffusion into underlying GM can drive chronic MS-like GM pathology. Lentiviral transfer vectors were injected into the sagittal sulcus of DA rats to deliver continuous expression of TNF + IFNγ transgenes in the meninges and the resulting neuropathology analysed after 1 and 2 months. Injection of TNF + IFNγ viral vectors, with or without prior MOG immunisation, induced extensive immune cell infiltration (CD4+ and CD8+ T-cells, CD79a + B-cells and macrophages) in the meninges by 28 dpi, which remained at 2 months. Control GFP viral vector did not induce infiltration. Subpial demyelination was seen underlying these infiltrates, which was partly dependant on prior myelin oligodendrocyte glycoprotein (MOG) immunisation. A significant decrease in neuronal numbers was seen at 28 and 56 days in cortical layers II-V that was independent of MOG immunisation. RNA analysis at 28 dpi showed an increase in expression of necroptotic pathway genes, including RIP3, MLKL, cIAP2 and Nox2. PhosphoRIP3+ and phosphoMLKL+ neurons were present in TNF + IFNγ vector injected animals, indicating activation of necroptosis. Our results suggest that persistent expression of TNF in the presence of IFNγ is a potent inducer of meningeal inflammation and can activate TNF signalling pathways in cortical cells leading to neuronal death and subpial demyelination and thus may contribute to clinical progression in MS.
Determination of the dipping direction of a blind reverse fault from InSAR: case study on the 2017 Sefid Sang earthquake, northeastern Iran
Authors: Ghayournajarkar Nematollah , Fukushima Yo 
Published: May 2020

AbstractDetermining the fault parameters of an earthquake is fundamental for studying the earthquake physics, understanding the seismotectonics of the region, and forecasting future earthquake activities in the surrounding area. Dense crustal deformation data such as Interferometric Synthetic Aperture Radar (InSAR) are useful for fault parameter determination, but determining the dipping direction of a blind fault is often challenging when the size of the earthquake is not large (M < 7) or when the coverage of the deformed area is limited to capture the details of rupture. The 5th April 2017, Mw 6.1 earthquake occurred near the city of Sefid Sang, northeast of Iran, provides an excellent case for exploring the potential of InSAR data for determining the dipping direction of a blind reverse fault. Using Advanced Land Observing Satellite-2 (ALOS-2) and Sentinel-1A interferograms of four different observation directions and a fault slip inversion method that allows thorough exploration of the fault geometry led to two candidates of reverse fault models, dipping either to the northeast or the south. The results show that the fault models of both dipping directions explain the data well, with a slight advantage in the northeast-dipping fault model in terms of the misfit when the atmospheric corrections were applied. The northeast-dipping fault model is, in addition, more consistent with the strike of the mapped active faults in the region and with the aftershock distribution, from which we infer that the 2017 Sefid Sang earthquake occurred on a northeast-dipping dextral-reverse fault. The preferred fault model has a strike angle of 314.8°, dip angle of 47.4° and rake angle of 130.3°, and a slip distribution of maximum 1.35 m at depth of 5 km equivalent to Mw 6.0. This study illuminates the difficulty of determining the dipping direction of blind faults even with InSAR measurements from multiple directions, but also that correcting for the atmospheric noise and comparing with other kinds of data can help infer the fault dipping direction.
Inter-observer variability of 90Y PET/CT dosimetry in hepatocellular carcinoma after glass microspheres transarterial radioembolization
Authors: Meyers Nicolas , Jadoul Alexandre , Bernard Claire , Delwaide Jean , Lamproye Anne , Detry Olivier , Honoré Pierre , Gerard Laurent , Hustinx Roland 
Published: May 2020

Abstract
Introduction
Strong correlation has been demonstrated between tumor dose and response and between healthy liver dose and side effects. Individualized dosimetry is increasingly recommended in the current clinical routine. However, hepatic and tumor segmentations could be complex in some cases. The aim of this study is to assess the reproducibility of the tumoral and non-tumoral liver dosimetry in selective internal radiation therapy (SIRT).

Material and methods
Twenty-three patients with hepatocellular carcinoma (HCC) who underwent SIRT with glass microspheres were retrospectively included in the study. Tumor (TV) and total liver volumes (TLV), and mean absorbed doses in tumoral liver (TD) and non-tumoral liver (THLD) were determined on the 90Y PET/CT studies using Simplicit90YTM software, by three independent observers. Dosimetry datasets were obtained by a medical physicist helped by a nuclear medicine (NM) physician with 10 years of experience (A), by a NM physician with 4-year experience (B), and by a resident who first performed 10 dosimetry assessments as a training (C). Inter-observer agreement was evaluated using intra-class correlation coefficients (ICC), coefficients of variation (CV), Bland-Altman plots, and reproducibility coefficient (RDC).

Results
A strong agreement was observed between all three readers for estimating TLV (ICC 0.98) and THLD (ICC 0.97). Agreement was lower for TV delineation (ICC 0.94) and particularly for TD (ICC 0.73), especially for the highest values. Regarding TD, the CV (%) was 26.5, 26.9, and 20.2 between observers A and B, A and C, and B and C, respectively, and the RDC was 1.5. Regarding THLD, it was 8.5, 12.7, and 9.4, and the RDC was 1.3.

Conclusion
Using a standardized methodology, and regardless of the different experiences of the observers, the estimation of THLD is highly reproducible. Although the reproducibility of the assessment of tumor irradiation is overall quite high, large variations may be observed in a limited number of patients.
Changed functional connectivity at rest in functional illiterates after extensive literacy training
Authors: Mohammadi Bahram , Münte Thomas F. , Cole David M. , Sami Amir , Boltzmann Melanie , Rüsseler Jascha 
Published: May 2020

AbstractBackgroundAbout 6.2 million adults in Germany cannot read and write properly despite attending school for several years. They are considered to be functional illiterates (FI). Since the ability to read and write is crucial for being employed and socially accepted, we developed a special literacy training to overcome these deficits.MethodsIn this study, we investigate training-related changes in intrinsic functional connectivity (iFC) at rest in a group of 20 FI and 20 adult normal readers using resting state functional magnetic resonance imaging (rsfMRI). We used independent component analysis (ICA) to define different networks.ResultsBefore training, the between group analysis showed increased iFC in FI in a left-fronto-parietal network (LFPN; anterior insula, medial frontal cortex, lateral and frontal parietal regions) and in the Basal Ganglia network (BGN: thalamus, caudate, putamen, pallidum, amygdala, supplementary motor cortex and cingulate gyrus). Furthermore, the Visual Network-1 (VN1; temporal occipital fusiform gyrus, lateral occipital cortex, occipital pole, lingual gyrus, thalamus) showed decreased iFC in FI. After training the FI group showed reversal of the “hyperconnectivity” in middle frontal gyrus and in the frontal orbital cortex and between supramarginal gyrus and the BGN. Furthermore, functional connectivity increased in FI VN1 (lateral occipital cortex, insular cortex). These changes in connectivity correlated with gains in reading speed and spelling accuracy.ConclusionsThese findings show that poor reading and writing abilities are associated with abnormalities in iFC in several brain areas subserving cognitive processes important for reading. Intensive literacy training induces changes in the functional connectivity between and within neural networks important for literacy skills.
Understanding the Barriers to Pediatric Oncologist Engagement and Accrual to Clinical Trials in National Cancer Institute–Designated Community Oncology Research Programs
Authors: Dickens David S. , Roth Michael E. , Pollock Brad H. , Langevin Anne-Marie 
Published: May 2020

PURPOSE: Clinical trial participation leads to progress in cancer care. Principal investigators (PIs) and clinical research associates (CRAs) play key roles in the provision and maintenance of clinical trial portfolios at their sites. Previous studies have evaluated the educational and resource needs of adult oncology providers, but nothing to date has focused on providers of pediatric oncology care. We aimed to identify the educational needs and clinical trial participation barriers at National Cancer Institute Community Oncology Research Program (NCORP) Children’s Oncology Group (COG) sites to improve the quality of site investigator engagement. METHODS: Quality improvement surveys of pediatric clinical research staff at NCORP sites were performed. The first was a web-based inquiry of NCORP COG PIs and lead CRAs to assess their general understanding of NCORP organizational structure and needs. The second survey of COG PIs was conducted by one-on-one telephone interviews aimed at identifying specific barriers to physician engagement and patient enrollment in clinical trial research. RESULTS: The majority of NCORP COG PIs and CRAs (63%) reported an incomplete understanding of NCORP structure, with approximately half expressing interest in developing stronger collaborations and engagement. Most NCORP COG PIs reported at least one shared barrier to clinical trial enrollment (78%), with inadequate protected time and research support (39% each) being the most frequently cited barriers. CONCLUSIONS: Contributions to pediatric cancer clinical research at COG NCORP sites could be enhanced through improved education, resources, and time allocation.