bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity, evolution, and classification of virophages uncovered through global metagenomics
Authors: Paez-Espino David , Zhou Jinglie , Roux Simon , Nayfach Stephen , Pavlopoulos Georgios A. , Schulz Frederik , McMahon Katherine D. , Walsh David , Woyke Tanja , Ivanova Natalia N. , Eloe-Fadrosh Emiley A. , Tringe Susannah G. , Kyrpides Nikos C. 
Published: December 2019

Abstract
Background
Virophages are small viruses with double-stranded DNA genomes that replicate along with giant viruses and co-infect eukaryotic cells. Due to the paucity of virophage reference genomes, a collective understanding of the global virophage diversity, distribution, and evolution is lacking.

Results
Here we screened a public collection of over 14,000 metagenomes using the virophage-specific major capsid protein (MCP) as “bait.” We identified 44,221 assembled virophage sequences, of which 328 represent high-quality (complete or near-complete) genomes from diverse habitats including the human gut, plant rhizosphere, and terrestrial subsurface. Comparative genomic analysis confirmed the presence of four core genes in a conserved block. We used these genes to establish a revised virophage classification including 27 clades with consistent genome length, gene content, and habitat distribution. Moreover, for eight high-quality virophage genomes, we computationally predicted putative eukaryotic virus hosts.

Conclusion
Overall, our approach has increased the number of known virophage genomes by 10-fold and revealed patterns of genome evolution and global virophage distribution. We anticipate that the expanded diversity presented here will provide the backbone for further virophage studies.
Fathers today: design of a randomized controlled trial examining the role of oxytocin and vasopressin in behavioral and neural responses to infant signals
Authors: Witte Annemieke M. , de Moor Marleen H. M. , van IJzendoorn Marinus H. , Bakermans-Kranenburg Marian J. 
Published: December 2019

AbstractBackgroundPrevious research has mostly focused on the hormonal, behavioral and neural correlates of maternal caregiving. We present a randomized, double-blind, placebo-controlled within-subject design to examine the effects of intranasal administration of oxytocin and vasopressin on parenting behavior and the neural and behavioral responses to infant cry sounds and infant threat. In addition, we will test whether effects of oxytocin and vasopressin administration are moderated by fathers’ early childhood experiences.MethodsFifty-five first-time fathers of a child between two and seven months old will participate in three experimental sessions with intervening periods of one to two weeks. Participants self-administer oxytocin, vasopressin or a placebo. Infant-father interactions and protective parenting responses are observed during play. Functional Magnetic Resonance Imaging (fMRI) is used to examine the neural processing of infant cry sounds and infant threat. A handgrip dynamometer is used to measure use of handgrip force when listening to infant cry sounds. Participants report on their childhood experiences of parental love-withdrawal and abuse and neglect.DiscussionThe results of this study will provide important insights into the hormonal, behavioral and neural correlates of fathers’ parenting behavior during the early phase of fatherhood.Trial registrationDutch Trial Register: NTR (ID:NL8124); Date registered: October 30, 2019.
Diagnosis and management of septal deviation and nasal valve collapse - a survey of Canadian otolaryngologists
Authors: Wang Yiqiao , Bonaparte James P. 
Published: December 2019

Background Management of nasal valve collapse (NVC) in patients with a septal deviation can be challenging. Our objective was to determine the opinions of Canadian Otolaryngologists regarding the diagnosis and management of nasal obstruction in patients with septal deviation and NVC. Methods A twenty-question survey was developed for the purpose of our study. Questions were divided into the following areas: diagnosis, management and prognosis. We included all otolaryngologists who were members of the Canadian Society of Otolaryngology. Results The response rate to our survey was 18%. The most commonly identified cause of a failed septoplasty was incomplete septoplasty (41.9%), followed by nasal valve collapse (25.6%). The Cottle manoeuvre (62.8%) and visual inspection (39.5%) were noted to be the most important diagnostic tools for external and internal NVC respectively. However, physicians often rely on a variable number of different examinations when making a diagnosis of nasal valve collapse. When evaluating which patients with a septal deviation also required nasal valve surgery, 27.9% of responders believed the current physical examination methods provided a high accuracy, while 55.8% indicated moderate accuracy and 16.3% indicated low accuracy. Compared to other subspecialties in Otolaryngology, Facial Plastic and Reconstruction Surgeons noted higher septoplasty failure rates in patients with co-morbid NVC. Conclusions NVC is an important concern for otolaryngologists performing septoplasty. Although most physicians believe that the physical exam provides a moderate effectiveness when predicting who requires a functional rhinoplasty, diagnostic methods used for NVC is varied and inconsistent.
Methylene blue inhibits Caspase-6 activity, and reverses Caspase-6-induced cognitive impairment and neuroinflammation in aged mice
Authors: Zhou Libin , Flores Joseph , Noël Anastasia , Beauchet Olivier , Sjöström P. Jesper , LeBlanc Andrea C. 
Published: December 2019

AbstractActivated Caspase-6 (Casp6) is associated with age-dependent cognitive impairment and Alzheimer disease (AD). Mice expressing human Caspase-6 in hippocampal CA1 neurons develop age-dependent cognitive deficits, neurodegeneration and neuroinflammation. This study assessed if methylene blue (MB), a phenothiazine that inhibits caspases, alters Caspase-6-induced neurodegeneration and cognitive impairment in mice. Aged cognitively impaired Casp6-overexpressing mice were treated with methylene blue in drinking water for 1 month. Methylene blue treatment did not alter Caspase-6 levels, assessed by RT-PCR, western blot and immunohistochemistry, but inhibited fluorescently-labelled Caspase-6 activity in acute brain slice intact neurons. Methylene blue treatment rescued Caspase-6-induced episodic and spatial memory deficits measured by novel object recognition and Barnes maze, respectively. Methylene blue improved synaptic function of hippocampal CA1 neurons since theta-burst long-term potentiation (LTP), measured by field excitatory postsynaptic potentials (fEPSPs) in acute brain slices, was successfully induced in the Schaffer collateral-CA1 pathway in methylene blue-treated, but not in vehicle-treated, Caspase-6 mice. Increased neuroinflammation, measured by ionized calcium binding adaptor molecule 1 (Iba1)-positive microglia numbers and subtypes, and glial fibrillary acidic protein (GFAP)-positive astrocytes, were decreased by methylene blue treatment. Therefore, methylene blue reverses Caspase-6-induced cognitive deficits by inhibiting Caspase-6, and Caspase-6-mediated neurodegeneration and neuroinflammation. Our results indicate that Caspase-6-mediated damage is reversible months after the onset of cognitive deficits and suggest that methylene blue could benefit Alzheimer disease patients by reversing Caspase-6-mediated cognitive decline.
Tau pathology in the medial temporal lobe of athletes with chronic traumatic encephalopathy: a chronic effects of neurotrauma consortium study
Authors: Kelley Christy M. , Perez Sylvia E. , Mufson Elliott J. 
Published: December 2019

AbstractChronic traumatic encephalopathy (CTE) is a progressive neurodegenerative condition associated with repetitive traumatic brain injury (rTBI) seen in contact-sport athletes and military personnel. The medial temporal lobe (MTL; i.e., hippocampus, subiculum, and entorhinal and perirhinal cortices) memory circuit displays tau lesions during the pathological progression of CTE. We examined MTL tissue obtained from 40 male Caucasian and African American athletes who received a postmortem CTE neuropathological diagnosis defined as stage II, III, or IV. Sections were immunolabeled using an early (AT8) or a late (TauC3) marker for pathological tau and for amyloid beta (Aβ) species (6E10, Aβ1–42and thioflavin S). Stereological analysis revealed that stage III had significantly less AT8-positive neurons and dystrophic neurites than stage IV in all MTL regions except hippocampal subfield CA3, whereas significantly more AT8-positive neurons, dystrophic neurites, and neurite clusters were found in the perirhinal cortex, entorhinal cortex, hippocampal CA1, and subiculum of CTE stage III compared with stage II. TauC3-positive pathology was significantly higher in the perirhinal and subicular cortex of stage IV compared to stage III and the perirhinal cortex of stage III compared to stage II. AT8-positive neurite clusters were observed in stages III and IV, but virtually absent in stage II. When observed, Aβ pathology appeared as amyloid precursor protein (APP)/Aβ (6E10)-positive diffuse plaques independent of region. Thioflavine S labeling, did not reveal evidence for fibril or neuritic pathology associated with plaques, confirming a diffuse, non-cored plaque phenotype in CTE. Total number of AT8-positive profiles correlated with age at death, age at symptom onset, and time from retirement to death. There was no association between AT8-positive tau pathology and age sport began, years played, or retirement age, and no difference between CTE stage and the highest level of sport played. In summary, our findings demonstrate different tau profiles in the MTL across CTE stages, proffering CA3 tau pathology and MTL dystrophic neurite clusters as possible markers for the transition between early (II) and late (III/IV) stages, while highlighting CTE as a progressive noncommunicative tauopathy.
Cellular alterations identified in pluripotent stem cell-derived midbrain spheroids generated from a female patient with progressive external ophthalmoplegia and parkinsonism who carries a novel variation (p.Q811R) in the POLG1 gene
Authors: Chumarina Margarita , Russ Kaspar , Azevedo Carla , Heuer Andreas , Pihl Maria , Collin Anna , Frostner Eleonor Åsander , Elmer Eskil , Hyttel Poul , Cappelletti Graziella , Zini Michela , Goldwurm Stefano , Roybon Laurent 
Published: December 2019

AbstractVariations in the POLG1 gene encoding the catalytic subunit of the mitochondrial DNA polymerase gamma, have recently been associated with Parkinson’s disease (PD), especially in patients diagnosed with progressive external ophthalmoplegia (PEO). However, the majority of the studies reporting this association mainly focused on the genetic identification of the variation in POLG1 in PD patient primary cells, and determination of mitochondrial DNA copy number, providing little information about the cellular alterations existing in patient brain cells, in particular dopaminergic neurons. Therefore, through the use of induced pluripotent stem cells (iPSCs), we assessed cellular alterations in novel p.Q811R POLG1 (POLG1Q811R) variant midbrain dopaminergic neuron-containing spheroids (MDNS) from a female patient who developed early-onset PD, and compared them to cultures derived from a healthy control of the same gender. Both POLG1 variant and control MDNS contained functional midbrain regionalized TH/FOXA2-positive dopaminergic neurons, capable of releasing dopamine. Western blot analysis identified the presence of high molecular weight oligomeric alpha-synuclein in POLG1Q811R MDNS compared to control cultures. In order to assess POLG1Q811R-related cellular alterations within the MDNS, we applied mass-spectrometry based quantitative proteomic analysis. In total, 6749 proteins were identified, with 61 significantly differentially expressed between POLG1Q811R and control samples. Pro- and anti-inflammatory signaling and pathways involved in energy metabolism were altered. Notably, increased glycolysis in POLG1Q811R MDNS was suggested by the increase in PFKM and LDHA levels and confirmed using functional analysis of glycolytic rate and oxygen consumption levels. Our results validate the use of iPSCs to assess cellular alterations in relation to PD pathogenesis, in a unique PD patient carrying a novel p.Q811R variation in POLG1, and identify several altered pathways that may be relevant to PD pathogenesis.
Beauty is skin deep: the skin tones of Vermeer’s Girl with a Pearl Earring
Authors: van Loon Annelies , Vandivere Abbie , Delaney John K. , Dooley Kathryn A. , De Meyer Steven , Vanmeert Frederik , Gonzalez Victor , Janssens Koen , Leonhardt Emilien , Haswell Ralph , de Groot Suzan , D’Imporzano Paolo , Davies Gareth R. 
Published: December 2019

Abstract
The soft modelling of the skin tones in Vermeer’s Girl with a Pearl Earring (Mauritshuis) has been remarked upon by art historians, and is their main argument to date this painting to c. 1665. This paper describes the materials and techniques Vermeer used to accomplish the smooth flesh tones and facial features of the Girl, which were investigated as part of the 2018 Girl in the Spotlight research project. It combines macroscopic X-ray fluorescence imaging (MA-XRF), reflectance imaging spectroscopy (RIS), and 3D digital microscopy. Vermeer built up the face, beginning with distinct areas of light and dark. He then smoothly blended the final layers to create almost seamless transitions. The combination of advanced imaging techniques highlighted that Vermeer built the soft contour around her face by leaving a ‘gap’ between the background and the skin. It also revealed details that were otherwise not visible with the naked eye, such as the eyelashes. Macroscopic imaging was complemented by the study of paint cross-sections using: light microscopy, SEM–EDX, FIB-STEM, synchrotron radiation µ-XRPD and FTIR–ATR. Vermeer intentionally used different qualities or grades of lead white in the flesh paints, showing different hydrocerussite/cerussite ratios and particle sizes. Lead isotope analysis showed that the geographic source of lead, from which the different types of lead white were manufactured, was the same: the region of Peak District of Derbyshire, UK. Finally, cross-section analysis identified the formation of new lead species in the paints: lead soaps and palmierite (K2Pb(SO4)2), associated with the red lake.
“I Broke Your Game!”: critique among middle schoolers designing computer games about climate change
Authors: Tucker-Raymond Eli , Puttick Gillian , Cassidy Michael , Harteveld Casper , Troiano Giovanni M. 
Published: December 2019

Abstract
Background
There have been increasing calls for integrating computational thinking and computing into school science, mathematics, and engineering classrooms. The learning goals of the curriculum in this study included learning about both computational thinking and climate science. Including computer science in science classrooms also means a shift in the focus on design and creation of artifacts and attendant practices. One such design practice, widespread in the design and arts fields, is critique. This paper explores the role of critique in two urban, heterogenous 8th grade science classrooms in which students engaged in creating computer games on the topic of climate systems and climate change. It explores and compares how practices of critique resulted from curricular decisions to (i) scaffold intentional critique sessions for student game designers and (ii) allow for spontaneous feedback as students interacted with each other and their games during the process of game creation.

Results
Although we designed formal opportunities for critique, the participatory dimension of the project meant that students were free to critique each other’s games at any time during the building process and did so voluntarily. Data indicate that students focused much more on the game play dimension of the design than the science, particularly in those critique sessions that were student-initiated. Despite the de-emphasis on science in spontaneous critiques, students still focused on several dimensions of computational thinking, considering user experience, troubleshooting, modeling, and elegance of solutions.

Conclusions
Students making games about science topics should have opportunities for both formal and spontaneous critiques. Spontaneous critiques allow for students to be authorities of knowledge and to determine what is acceptable and what is not. However, formal, teacher-designed critiques may be necessary for students to focus on science as part of the critique. Furthermore, one of the benefits to critiquing others was that students were able to see what others had done, how they had set up their games, the content they included, and how they had programmed certain features. Lastly, critiques can help facilitate iteration as students work to improve their games.
Five years of development in pursuing excellence in quality and global impact to become the first journal in STEM education covered in SSCI
Authors: Li Yeping 
Published: December 2019

AbstractWith the completion of its first five publication cycle years (August 2014 to July 2019), the International Journal of STEM Education has made great progress with its commitments to pursue excellence in quality and worldwide impact. In this editorial, I specifically share the journal’s achievements since August 2018 in obtaining Scopus’s CiteScore and for being included in Web of Science’s Social Sciences Citation Index (SSCI), which reflect the journal’s continued growth with on-going strong support from researchers and readers internationally.
Four hours of veno-venous extracorporeal membrane oxygenation using bi-caval cannulation affects kidney function and induces moderate lung damage in a mouse model
Authors: Natanov Ruslan , Khalikov Abdurasul , Gueler Faikah , Maus Ulrich , Boyle Erin C. , Haverich Axel , Kühn Christian , Madrahimov Nodir 
Published: December 2019

Abstract
Background
Improvement of single site cannulation for extracorporeal membrane oxygenation (ECMO) therapy is pivotal for reduction of patient morbidity and mortality in respiratory failure. To further improve the cardiopulmonary outcomes and reduce end organ damage, we established a murine model for single site cannulation with a double lumen cannula.

Results
We created a hemodynamically stable double lumen cannula and successfully implanted it through the jugular vein into the upper and lower vena cava. This allowed adequate drainage of the blood. Blood gas analysis showed excellent oxygenation and CO2 reduction. There was no excessive bleeding. No signs of right heart congestion were present which was confirmed in the histological analysis of the liver. Histology demonstrated moderate lung damage and mild acute kidney injury. Neutrophil infiltration was similar in ECMO and sham kidneys.

Conclusions
Veno-venous extracorporeal circulation deteriorates kidney function and promotes moderate pulmonary damage.
Radiological semantics discriminate clinically significant grade prostate cancer
Authors: Li Qian , Lu Hong , Choi Jung , Gage Kenneth , Feuerlein Sebastian , Pow-Sang Julio M. , Gillies Robert , Balagurunathan Yoganand 
Published: December 2019

AbstractBackgroundIdentification of imaging traits to discriminate clinically significant prostate cancer is challenging due to the multi focal nature of the disease. The difficulty in obtaining a consensus by the Prostate Imaging and Data Systems (PI-RADS) scores coupled with disagreements in interpreting multi-parametric Magnetic Resonance Imaging (mpMRI) has resulted in increased variability in reporting findings and evaluating the utility of this imaging modality in detecting clinically significant prostate cancer. This study assess the ability of radiological traits (semantics) observed on multi-parametric Magnetic Resonance images (mpMRI) to discriminate clinically significant prostate cancer.MethodsWe obtained multi-parametric MRI studies from 103 prostate cancer patients with 167 targeted biopsies from a single institution. The study was approved by our Institutional Review Board (IRB) for retrospective analysis. The biopsy location had been identified and marked by a clinical radiologist for targeted biopsy based on initial study interpretation. Using the target locations, two study radiologists independently re-evaluated the scans and scored 16 semantic traits on a point scale (up to 5 levels) based on mpMRI images. The semantic traits describe size, shape, and border characteristics of the prostate lesion, as well as presence of disease around lymph nodes (lymphadenopathy). We built a linear classifier model on these semantic traits and related to pathological outcome to identify clinically significant tumors (Gleason Score ≥ 7). The discriminatory ability of the predictors was tested using cross validation method randomly repeated and ensemble values were reported. We then compared the performance of semantic predictors with the PI-RADS predictors.ResultsWe found several semantic features individually discriminated high grade Gleason score (ADC-intensity, Homogeneity, early-enhancement, T2-intensity and extraprostatic extention), these univariate predictors had an average area under the receiver operator characteristics (AUROC) ranging from 0.54 to 0.68. Multivariable semantic predictors with three features (ADC-intensity; T2-intensity, enhancement homogenicity) had an average AUROC of 0.7 [0.43, 0.94]. The PI-RADS based predictor had average AUROC of 0.6 [0.47, 0.75].ConclusionWe find semantics traits are related to pathological findings with relatively higher reproducibility between radiologists. Multivariable predictors formed on these traits shows higher discriminatory ability compared to PI-RADS scores.
Yield models for predicting aboveground ectomycorrhizal fungal productivity in Pinus sylvestris and Pinus pinaster stands of northern Spain
Authors: Sánchez-González Mariola , de-Miguel Sergio , Martin-Pinto Pablo , Martínez-Peña Fernando , Pasalodos-Tato María , Oria-de-Rueda Juan Andrés , Martínez de Aragón Juan , Cañellas Isabel , Bonet José Antonio 
Published: December 2019

AbstractBackgroundPredictive models shed light on aboveground fungal yield dynamics and can assist decision-making in forestry by integrating this valuable non-wood forest product into forest management planning. However, the currently existing models are based on rather local data and, thus, there is a lack of predictive tools to monitor mushroom yields on larger scales.ResultsThis work presents the first empirical models for predicting the annual yields of ectomycorrhizal mushrooms and related ecosystem services inPinus sylvestrisandPinus pinasterstands in northern Spain, using a long-term dataset suitable to account for the combined effect of meteorological conditions and stand structure. Models were fitted for the following groups of fungi separately: all ectomycorrhizal mushrooms, edible mushrooms and marketed mushrooms. Our results show the influence of the weather variables (mainly precipitation) on mushroom yields as well as the relevance of the basal area of the forest stand that follows a right-skewed unimodal curve with maximum predicted yields at stand basal areas of 30–40 m2∙ha− 1.ConclusionThese models are the first empirical models for predicting the annual yields of ectomycorrhizal mushrooms inPinus sylvestrisandPinus pinasterstands in northern Spain, being of the highest resolution developed to date and enable predictions of mushrooms productivity by taking into account weather conditions and forests’ location, composition and structure.