bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of Formaldehyde in Tofu by Sequential Injection Analysis Using Acetoacetanilide as Hantzsch Reaction Reagent
Authors: Nabila Rista , Sulistyarti Hermin , Wisang Yohanna Felisita , Sabarudin Akhmad
Published: June 2019

Formaldehyde is a toxic and dangerous compound that is still often used freely by irresponsible traders or producers as food additives. At low concentrations, formaldehyde can cause eye, nose, throat and skin irritations. Exposure to large amounts of formaldehyde can cause severe pain, vomiting, coma, and even death. According to the International Program on Chemical Safety (IPCS), the threshold for formaldehyde in food that can still be tolerated in adult bodies is 1.5 mg to 14 mg per day while in a drinking water is 0.1 ppm. Determination of formaldehyde generally employ a titration method, which requires a large amount of sample and reagent, and long analysis time. This work aims to determine the formaldehyde in tofu commercially available in traditional markets of Malang City by Sequential Injection Analysis method using acetoacetanilide (AAA) at optimum conditions. Determination of formaldehyde is based on the Hantzsch reaction, which involves a cyclization between AAA and formaldehyde in the presence of ammonia so that it will produce a yellow dihydropyridine derivative product detected at a wavelength of 359 nm. The optimum condition for the formation of the reaction product occurred at an AAA concentration of 0.03 M, an ammonium acetate concentration of 1.5 M, a reaction time of 50 s and a flow rate of 75 µL/s. Excellent sensitivity and accuracy could be attributed to our developed formaldehyde detection method as the detection limit of 4.5 ppb and the recovery values of > 95 were achieved. Low reagent consumption, less waste production, and high throughput analysis are other advantages of our proposed method.
Dynamic Analysis of a Tumor Treatment Model Using Oncolytic Virus and Chemotherapy with Saturated Infection Rate
Authors: Ontah Glorya Marseli , Trisilowati  , Darti Isnani
Published: June 2019

Virotherapy is one of the most promising therapies in the treatment of tumors which may be further combined with chemotherapy to accelerate the healing rate. In this article, we propose a mathematical model for the treatment of tumors using oncolytic virus and chemotherapy. This model takes the form of nonlinear ordinary differential equations describing the interactions between uninfected tumor cells, infected tumor cells, an oncolytic virus, and chemotherapy. It is assumed that the rate of infection between uninfected tumor cells and infected tumor cells is in a saturated form. The saturation effect takes into account the fact that the number of contacts between them reaches the maximum value when the immune system works to stop the virus. The dynamical analysis, which includes the existence of equilibrium points, and its stability analysis is investigated. The analysis result shows that the system has three equilibrium points: tumor-free equilibrium point, virus-free equilibrium point and endemic equilibrium point. It is proven that these equilibrium points are conditionally stable. The numerical simulations show the successful combination of chemotherapy and virotherapy using an oncolytic virus in eliminating the tumor cells.
Microfluidic Paper based Analytical Device (µpads) for Analysis of Benzoat Acid in Packaged Beverages
Authors: Sari M I , Andayani Ulfa , Anneke  , Andini  , Sabarudin Akhmad
Published: June 2019

Microfluidic Paper-based Analytical Devices (μPADs) are a simple analytical platform that satisfy combination of low cost, portability, and ease-to-use with selectivity, sensitivity, and accuracy. In this experiment, the μPADs devices are prepared using a chromatographic paper and designed at appropriate pattern prior to printing by mean of a solid ink (wax) printer to produce hydrophobic barriers and hydrophilic channels. Then, the μPADs are heated at 120°C for 3 min to allow a wax penetrates in the both side of a paper. The resulted μPADs are used for the detection of benzoic acid through alkalimetry principle. For this purpose, the devices are implanted with 5M NaOH in the detection zone and a 2% phenolphthalein indicator in the sample zone before dried in open air. When the devices have dried, the μPADs are ready to be used to detect benzoic acid. To avoid color interferences, the samples are distilled before introduced to the sample zone for quantitative detection. The result soft the color changes can be immediately seen by naked eye, and their intensities are quantified by the Image J software. Excellent linearity is achieved in the range of benzoic acid concentration of 20-120 ppm with the linear equation of Y = 0.0102 x + 0.0077 and the correlation coefficient (R2) of 0.9999. The optimized μPADs devices are successfully applied to the quantitative analysis of benzoic acid in the 5 kinds of commercially packaged beverages. There is no significantly different of the analytical results obtained by the µPADs in comparison to the spectrophotometric method. Overall, the results obtained in this study indicate that the μPADs devices are a reliable tool for high throughout and on-site determination of benzoic acid content in commercial drinks.
Electrical Transport and magnetoresistance properties of La0.8Ca0.2-xAgxMnO3 (x = 0 and 0.05)
Authors: Razaq Dhawud Sabilur , Kurniawan Budhy , Imaddudin Agung , Sahara Nabila Aisyah , Munazat Dicky Rezky
Published: June 2019

A systematic investigation of electrical transport and magnetoresistance properties of polycrystalline La0.8Ca0.2-xAgxMnO3 (x = 0 and 0.05) is reported in this work. According to the resistivity data measured from 40 to 250 K, transition from metallic to insulator behavior upon heating were observed in both samples. Additionally, 5% silver substitution shifts the metal-semiconductor transition into a higher temperature. Furthermore, silver substitution also decreases the overall temperature compared to the original compound. In this work, this result can be well described using electron-electron, electron-phonon, and the interaction between electron, phonon, and magnon. Resistivity measurements under magnetic field influence shows that silver substitution improves the magnetoresistance properties compared to the original compound. The maximum ratio of magnetoresistance at 285 K was found to be 3.3% and 4.7% for x = 0 and 0.05, respectively.
Synaesthesia: A Very Short Introduction
Authors: Simner Julia
Published: June 2019

Synaesthesia is often described as a rare neurological condition where one sense appears to merge or cross with another. It is a multi-variant condition that can present itself in many different ways: some synaesthetes taste words, while others see colours when they hear sounds. Synaesthesia: A Very Short Introduction describes this extraordinary condition, explaining what synaesthesia is, how it manifests itself, what causes it, how it feels, how it links to creativity and the arts, and what it can tell us about every human’s perceptions of reality. Delving into the neuroscience behind synaesthesia, it also relates contemporary attempts at understanding both the genetic causes of synaesthesia, and how synesthetic sensations occur in the brain.
2. Synaesthesia in the brain
Authors: Simner Julia
Published: June 2019

Advances in brain imaging have revolutionised the study of synaesthesia and have enormous potential in educating us about the aetiology of this unusual condition. Brain scans provide clear and irrefutable evidence of how synaesthetic sensations are grounded in the brain. ‘Synaesthesia in the brain’ describes several seminal studies in the brain imaging of synaesthesia, which have involved a mixture of techniques: positron emission tomography, functional magnetic resonance imaging, and diffusion tensor imaging. Two key questions have been considered: do synaesthetes have functional or structural differences in their brains, and are their direct or indirect connections between the different parts of the brains that are triggered by different senses?
4. Is synaesthesia a ‘gift’ or a ‘condition’?
Authors: Simner Julia
Published: June 2019

Is there a consequence to having synaesthesia, even beyond the obvious difference of experiencing merged sensations? Do synaesthetes also have qualities that make them different to non-synaesthetes in other ways? Do they show differences in everyday abilities like memory, mental calculation, general perception, creative thinking, use-of-language and so on? ‘Is synaesthesia a “gift” or a “condition”?’ describes studies that show synaesthetes are objectively more creative than the average person, and have certain personality traits linked to heightened imagination. Synaesthetes also have specific visual benefits, such as the ability to better distinguish facial features and their expressions. Synaesthesia appears to come with a number of benefits, but it can also bring challenges.
6. The question of synaesthesia
Authors: Simner Julia
Published: June 2019

‘The question of synaesthesia’ looks at arguments against the Neonatal Synaesthesia Hypothesis and at other controversies and outstanding issues facing the field. It discusses the consistency-over-time feature and explains that although synaesthetes are highly consistent, they are not necessarily 100% consistent, and some synaesthetes might not be consistent at all. Is synaesthesia truly consistent over time as a definitional criterion, or does consistency over time merely characterize a subset of synaesthetes? There is also an imbalance between understanding the synaesthetes in English-speaking cultures and understanding synaesthetes worldwide, as well as between different types of synaesthesias. Despite the huge recent advances in understanding synaesthesia and how it affects synaesthetes, there is still more to learn.
2. Extinction today and efforts to stop it
Authors: Wignall Paul B.
Published: June 2019

The fossil record shows that life has experienced five major mass extinctions. A sixth catastrophe may be underway. Past mass extinctions were geologically short-lived intense crises that affected animals and plants in all environments. They removed the dominant and abundant species, leaving ecological voids to be filled by groups that were often rare or insignificant beforehand. Uniquely, the big five also saw the collapse of the base of the food chain in the oceans. The current extinction crisis does not yet have any of these attributes, but there are concerns over rising species extinction rates. ‘Extinction today and efforts to stop it’ compares current extinction rates with those of the past, and considers different terrestrial and marine conservation approaches.
4. Fossil hominins
Authors: Wood Bernard
Published: June 2019

Palaeoanthropologists use many methods to work out the significance of newly discovered fossil evidence, but the first task is to assign hominin fossils to a taxon. After that researchers work out that taxon’s relationships with other fossil and living taxa, and then they infer the behaviours and habitat preferences of the taxon. ‘Fossil hominins: analysis and interpretation’ explains the workings of classification and taxonomy. It describes how whole fossils can be reconstructed from fragments; the difficulties of determining the sex and developmental age of hominin fossil remains; the different interpretations of speciation; how cladistics analysis works; and the gaps and biases in the hominin fossil record.
Literal self-deception
Authors: Jordan Maiya
Published: June 2019

It is widely assumed that a literal understanding of someone’s self-deception that p yields the following contradiction. Qua self-deceiver, she does not believe that p, yet – qua self-deceived – she does believe that p. I argue that this assumption is ill-founded. Literalism about self-deception – the view that self-deceivers literally self-deceive – is not committed to this contradiction. On the contrary, properly understood, literalism (non-trivially) excludes it.
Validation of a simple equation for glomerular filtration rate measurement based on plasma iohexol disappearance
Authors: Ng Derek K , Levey Andrew S , Shlipak Michael G , Muñoz Alvaro , Inker Lesley A , Shafi Tariq
Published: June 2019

Background

A simple equation for glomerular filtration rate (GFR) measurement based on only plasma samples during the slow compartment after injection of iohexol was previously developed among children with chronic kidney disease and adult men with or at risk of HIV infection [Chronic Kidney Disease in Children (CKiD)-Multicenter AIDS Cohort Study (MACS) equation], but has not been externally validated. We aimed to evaluate the performance of the CKiD-MACS equation among elderly participants in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort who underwent directly measured iohexol GFR.

Methods

Using data from 287 participants of the MESA-Kidney study who underwent a five-sample measured iohexol GFR (two and three samples in the fast and slow compartments, respectively), we assessed the performance of the CKiD-MACS equation using only plasma samples in the slow compartment by sex, race and age. Agreement was assessed by bias, correlation, proportion within 5 and 10%, and the root mean square error (RMSE).

Results

The average age and GFR of the participants were 71 years and 70.8 mL/min/1.73 m2, respectively, and 46% were black. The equation yielded excellent agreement within stratified groups with high correlation (>0.96), low bias (≤1.2 mL/min/1.73 m2) and low RMSE (<4.2 mL/min/1.73 m2).

Conclusions

The CKiD-MACS equation demonstrated valid GFR measurement using only samples in the slow compartment in this racially diverse, elderly population. While the equation yielded practically the same results as the original Brochner-Mortensen equation, the CKiD-MACS equation conforms to theoretical principles embedded in the two-compartment model of direct GFR measurement.
Spatial analysis of demand for sparsely located ecosystem services using alternative index approaches
Authors: Granado-Díaz Rubén , Gómez-Limón José A , Rodríguez-Entrena Macario , Villanueva Anastasio J
Published: June 2019

This study focuses on the effects of spatial discounting and substitutes sites on the demand for ecosystem services (ES) provided by scattered agroecosystems. New ways of modelling these two effects are proposed, relying on area-based and density-based indices. Data from discrete choice experiments are used, based on a case study of Andalusian olive groves (southern Spain). The results show that model fit is significantly improved by the introduction of these spatial indices, with the best outcome found for the area-based index combined with the inverse of the distance. Results provide evidence of substantial spatial heterogeneity depending on the ES (carbon sequestration, soil conservation and biodiversity), indicating different economic jurisdictions.
Dosage Compensation throughout the Schistosoma mansoni Lifecycle: Specific Chromatin Landscape of the Z Chromosome
Authors: Picard Marion A L , Vicoso Beatriz , Roquis David , Bulla Ingo , Augusto Ronaldo C , Arancibia Nathalie , Grunau Christoph , Boissier Jérôme , Cosseau Céline
Published: June 2019

Differentiated sex chromosomes are accompanied by a difference in gene dose between X/Z-specific and autosomal genes. At the transcriptomic level, these sex-linked genes can lead to expression imbalance, or gene dosage can be compensated by epigenetic mechanisms and results into expression level equalization. Schistosoma mansoni has been previously described as a ZW species (i.e., female heterogamety, in opposition to XY male heterogametic species) with a partial dosage compensation, but underlying mechanisms are still unexplored. Here, we combine transcriptomic (RNA-Seq) and epigenetic data (ChIP-Seq against H3K4me3, H3K27me3, and H4K20me1 histone marks) in free larval cercariae and intravertebrate parasitic stages. For the first time, we describe differences in dosage compensation status in ZW females, depending on the parasitic status: free cercariae display global dosage compensation, whereas intravertebrate stages show a partial dosage compensation. We also highlight regional differences of gene expression along the Z chromosome in cercariae, but not in the intravertebrate stages. Finally, we feature a consistent permissive chromatin landscape of the Z chromosome in both sexes and stages. We argue that dosage compensation in schistosomes is characterized by chromatin remodeling mechanisms in the Z-specific region.
Associations of Awareness of Age-Related Change With Emotional and Physical Well-being: A Systematic Review and Meta-analysis
Authors: Sabatini Serena , Silarova Barbora , Martyr Anthony , Collins Rachel , Ballard Clive , Anstey Kaarin J , Kim Sarang , Clare Linda
Published: June 2019

Background and Objectives

This systematic review aimed to synthesize and quantify the associations of awareness of age-related change (AARC) with emotional well-being, physical well-being, and cognitive functioning.

Research Design and Methods

We conducted a systematic review with a correlational random effects meta-analysis. We included quantitative studies, published from January 1, 2009 to October 3, 2018, exploring associations between AARC and one or more of the following outcomes: emotional well-being, physical well-being, and cognitive functioning. We assessed heterogeneity (I2) and publication bias.

Results

We included 12 studies in the review, 9 exploring the association between AARC and emotional well-being and 11 exploring the association between AARC and physical well-being. No study explored the association between AARC and cognitive functioning. Six articles were included in the meta-analysis. We found a moderate association between a higher level of AARC gains and better emotional well-being (r = .33; 95% CI 0.18, 0.47; p <.001; I2 = 76.01) and between a higher level of AARC losses and poorer emotional (r = −.31; 95% CI −0.38, −0.24; p < .001; I2 = 0.00) and physical well-being (r = −.38; 95% CI −0.51, −0.24; p < .001; I2 = 83.48). We found a negligible association between AARC gains and physical well-being (r = .08; 95% CI 0.02, 0.14; p < .122; I2 = 0.00). Studies were of medium to high methodological quality.

Discussion and Implications

There is some indication that AARC gains and losses can play a role in emotional well-being and that AARC losses are associated with physical well-being. However, the number of included studies is limited and there was some indication of heterogeneity.

PROSPERO Registration

CRD42018111472.
A collection of yeast cellular electron cryotomography data
Authors: Gan Lu , Ng Cai Tong , Chen Chen , Cai Shujun
Published: June 2019

Background

Cells are powered by a large set of macromolecular complexes, which work together in a crowded environment. The in situ mechanisms of these complexes are unclear because their 3D distribution, organization, and interactions are largely unknown. Electron cryotomography (cryo-ET) can address these knowledge gaps because it produces cryotomograms—3D images that reveal biological structure at ~4-nm resolution. Cryo-ET uses no fixation, dehydration, staining, or plastic embedment, so cellular features are visualized in a life-like, frozen-hydrated state. To study chromatin and mitotic machinery in situ, we subjected yeast cells to genetic and chemical perturbations, cryosectioned them, and then imaged the cells by cryo-ET.

Findings

Here we share >1,000 cryo-ET raw datasets of cryosectioned budding yeast Saccharomyces cerevisiaecollected as part of previously published studies. These data will be valuable to cell biologists who are interested in the nanoscale organization of yeasts and of eukaryotic cells in general. All the unpublished tilt series and a subset of corresponding cryotomograms have been deposited in the EMPIAR resource for the community to use freely. To improve tilt series discoverability, we have uploaded metadata and preliminary notes to publicly accessible Google Sheets, EMPIAR, and GigaDB.

Conclusions

Cellular cryo-ET data can be mined to obtain new cell-biological, structural, and 3D statistical insights in situ. These data contain structures not visible in traditional electron-microscopy data. Template matching and subtomogram averaging of known macromolecular complexes can reveal their 3D distributions and low-resolution structures. Furthermore, these data can serve as testbeds for high-throughput image-analysis pipelines, as training sets for feature-recognition software, for feasibility analysis when planning new structural-cell-biology projects, and as practice data for students.
Pediatric Inflammatory Bowel Disease Complications Are More Likely on the Weekend
Authors: Menchini Cortney Ballengee
Published: June 2019

Weekend surgical hospitalizations for pediatric IBD have increased risk for complications as compared with weekdays per a new study by Egberg et al. Further research may elicit the prevalence and etiology of this weekend effect. Appropriately utilizing emergency departments might decrease complications.
A nonparametric updating method to correct clinical prediction model drift
Authors: Davis Sharon E , Greevy Robert A , Fonnesbeck Christopher , Lasko Thomas A , Walsh Colin G , Matheny Michael E
Published: June 2019

Objective

Clinical prediction models require updating as performance deteriorates over time. We developed a testing procedure to select updating methods that minimizes overfitting, incorporates uncertainty associated with updating sample sizes, and is applicable to both parametric and nonparametric models.

Materials and Methods

We describe a procedure to select an updating method for dichotomous outcome models by balancing simplicity against accuracy. We illustrate the test’s properties on simulated scenarios of population shift and 2 models based on Department of Veterans Affairs inpatient admissions.

Results

In simulations, the test generally recommended no update under no population shift, no update or modest recalibration under case mix shifts, intercept correction under changing outcome rates, and refitting under shifted predictor-outcome associations. The recommended updates provided superior or similar calibration to that achieved with more complex updating. In the case study, however, small update sets lead the test to recommend simpler updates than may have been ideal based on subsequent performance.

Discussion

Our test’s recommendations highlighted the benefits of simple updating as opposed to systematic refitting in response to performance drift. The complexity of recommended updating methods reflected sample size and magnitude of performance drift, as anticipated. The case study highlights the conservative nature of our test.

Conclusions

This new test supports data-driven updating of models developed with both biostatistical and machine learning approaches, promoting the transportability and maintenance of a wide array of clinical prediction models and, in turn, a variety of applications relying on modern prediction tools.
Body temperature patterns vary with day, season, and body condition of moose (Alces alces)
Authors: Thompson Daniel P , Barboza Perry S , Crouse John A , McDonough Thomas J , Badajos Oriana H , Herberg Andrew M
Published: June 2019

Variation in core body temperature of mammals is a result of endogenous regulation of heat from metabolism and the environment, which is affected by body size and life history. We studied moose (Alces alces) in Alaska to examine the effects of endogenous and exogenous factors on core body temperature at seasonal and daily time scales. We used a modified vaginal implant transmitter to record core body temperature in adult female moose at 5-min intervals for up to 1 year. Core body temperature in moose showed a seasonal fluctuation, with a greater daily mean core body temperature during the summer (38.2°C, 95% CI = 38.1–38.3°C) than during the winter (37.7°C, 95% CI = 37.6–37.8°C). Daily change in core body temperature was greater in summer (0.92°C, 95% CI = 0.87–0.97°C) than in winter (0.58°C, 95% CI = 0.53–0.63°C). During winter, core body temperature was lower and more variable as body fat decreased among female moose. Ambient temperature and vapor pressure accounted for a large amount of the residual variation (0.06–0.09°C) in core body temperature after accounting for variation attributed to season and individual. Ambient temperature and solar radiation had the greatest effect on the residual variation (0.17–0.20°C) of daily change in core body temperature. Our study suggests that body temperature of adult female moose is influenced by body reserves within seasons and by environmental conditions within days. When studying northern cervids, the influence of season and body condition on daily patterns of body temperature should be considered when evaluating thermal stress.
Anal abscess due to leech therapy of hemorrhoids: mumbo jumbo is still in vogue
Authors: Menteş B Bülent , Leventoğlu Sezai , Osmanov İgbal , Kösehan Dilek , Erol Timuçin
Published: June 2019

Anorectal sepsis usually presents with anal abscesses, which may evolve to become anorectal fistulas. Most of these cases are either of cryptoglandular origin, or they develop secondary to inflammatory bowel diseases. A 32-year-old male patient applied to our Proctology Unit with severe anal pain and swelling. Three days before admission, leeches were applied to the hemorrhoidal swellings in a medical center. The abscess was drained with appropriate unroofing and search for any compartments. The patient recovered rapidly. The abscess culture and microscopy revealed mix flora with predominant Escherichia coli. After 6 months, he has been symptom-free with perfect healing of the surgical site. We need to check up on possible handicaps in our modern patient care policies that divert people to such methods. Nevertheless, such alternative methods should be regarded as nonscientific and out of context unless their efficacy and safety are documented.
High-yielding rice Takanari has superior photosynthetic response to a commercial rice Koshihikari under fluctuating light
Authors: Adachi Shunsuke , Tanaka Yu , Miyagi Atsuko , Kashima Makoto , Tezuka Ayumi , Toya Yoshihiro , Kobayashi Shunzo , Ohkubo Satoshi , Shimizu Hiroshi , Kawai-Yamada Maki , Sage Rowan F , Nagano Atsushi J , Yamori Wataru
Published: June 2019

The high-yielding rice cultivar Takanari has fast photosynthetic induction owing to a high electron transport rate, stomatal conductance, and metabolic flux, leading to high daily carbon gain under fluctuating light.
Big Data Governance Needs More Collective Responsibility: The Role of Harm Mitigation in the Governance of Data Use in Medicine and Beyond
Authors: McMahon Aisling , Buyx Alena , Prainsack Barbara
Published: June 2019

Harms arising from digital data use in the big data context are often systemic and cannot always be captured by linear cause and effect. Individual data subjects and third parties can bear the main downstream costs arising from increasingly complex forms of data uses—without being able to trace the exact data flows. Because current regulatory frameworks do not adequately address this situation, we propose a move towards harm mitigation tools to complement existing legal remedies. In this article, we make a normative and practical case for why individuals should be offered support in such contexts and how harm mitigation tools can achieve this. We put forward the idea of ‘Harm Mitigation Bodies’ (HMBs), which people could turn to when they feel they were harmed by data use but do not qualify for legal remedies, or where existing legal remedies do not address their specific circumstances. HMBs would help to obtain a better understanding of the nature, severity, and frequency of harms occurring from both lawful and unlawful data use, and they could also provide financial support in some cases. We set out the role and form of these HMBs for the first time in this article.
Combining Ab Interno Kahook Trabeculectomy with Gonioscopy-Assisted Transluminal Trabeculotomy Reduces Intraocular Pressure
Authors: Widder Jared R , Schmitz Joseph W
Published: June 2019

Minimally invasive glaucoma surgery (MIGS) provides a safe option for individuals with mild to moderate open-angle glaucoma to reduce their need for pharmacologic therapy or more extensive ab externo surgeries. In this report, we describe a surgical technique using both the Kahook Dual Blade and Gonioscopy-assisted transluminal trabeculotomy (GATT), to treat a 23-year-old active duty female with idiopathic uveitis and subsequent corticosteroid-induced glaucoma who presented with consistently elevated intraocular pressure (IOP) measurements despite maximal pharmacologic interventions. This combination was effective in consistently lowering intraocular pressure for at least 12 months in a young, phakic, active duty patient with uveitis and steroid-responsive open-angle glaucoma.
Coevolution of Sites under Immune Selection Shapes Epstein–Barr Virus Population Structure
Authors: Wegner Fanny , Lassalle Florent , Depledge Daniel P , Balloux François , Breuer Judith
Published: June 2019

Epstein–Barr virus (EBV) is one of the most common viral infections in humans and persists within its host for life. EBV therefore represents an extremely successful virus that has evolved complex strategies to evade the host’s innate and adaptive immune response during both initial and persistent stages of infection. Here, we conducted a comparative genomics analysis on 223 whole genome sequences of worldwide EBV strains. We recover extensive genome-wide linkage disequilibrium (LD) despite pervasive genetic recombination. This pattern is explained by the global EBV population being subdivided into three main subpopulations, one primarily found in East Asia, one in Southeast Asia and Oceania, and the third including most of the other globally distributed genomes we analyzed. Additionally, sites in LD were overrepresented in immunogenic genes. Taken together, our results suggest that host immune selection and local adaptation to different human host populations has shaped the genome-wide patterns of genetic diversity in EBV.
Combined Internal Maxillary Artery to Middle Cerebral Artery and In Situ Middle Cerebral to Middle Cerebral Artery Bypass for Complex Middle Cerebral Artery Aneurysm: 3-Dimensional Operative Video
Authors: White Timothy G , Klironomos Georgios , Langer David J , Katz Jeffrey , Dehdashti Amir R
Published: June 2019

Flow-replacement revascularization and/or flow augmentation surgery may be necessary for safe deconstruction of complex middle cerebral artery (MCA) aneurysms. Roughly 1% to 2% of all MCA aneurysms have angiographic features prohibiting standard microsurgical or endovascular management. Consent was obtained from the patient for the production of this video. No International Review Board approval was required for the creation of this video. A 17-yr-old female presented at the age of 15 with headaches. At the time of initial presentation, the patient was found to have an MCA bifurcation aneurysm. Initially, the aneurysm was managed conservatively and followed. However, on follow-up imaging, the aneurysm was found to have grown and developed into a large, complex MCA bifurcation aneurysm. Patient underwent planned trapping and deconstruction of the aneurysm. An internal maxillary artery (IMAX) to MCA bypass was performed using a cephalic vein graph to a robust inferior MCA branch combined with an in Situ MCA to MCA bypass. Follow-up angiography showed complete occlusion of the aneurysm. Patient was neurologically intact at 1-yr follow-up. Microsurgery continues to be the best treatment option for complex MCA aneurysms. A surgeon trained in bypass is an absolute prerequisite for management of those lesions. The IMAX offers an ideal high flow donor vessel for subcranial to intracranial flow replacement, which was required for re-establishment of flow to the robust inferior MCA branch in this case. The superior branch of the MCA was less robust. Therefore, by recreating a more distal bifurcation, the in Situ side-to-side MCA-MCA bypass simplified the revascularization strategy.
Adapting to Space Limitations During Prone Real-Time Magnetic Resonance Imaging-Guided Stereotaxic Laser Ablation: Technical Pearls
Authors: Zervos Thomas M , Scarpace Lisa , Robin Adam M , Schwalb Jason M , Air Ellen L
Published: June 2019

BACKGROUND

New techniques of intraoperative magnetic resonance imaging (MRI)-guided stereotaxy enable minimally invasive approaches to intracranial pathology. Laser interstitial thermal therapy (LITT), convection-enhanced drug delivery, and stereotactic biopsy can be performed with a real-time confirmation of location and the ability to adjust for intracranial shift during the procedure. However, these procedures are constrained by patient positioning and the need for trajectories that avoid collision between stereotactic elements and the small MRI bore. To our knowledge, this is the first report to outline the technical details of safe intraoperative MRI (iMRI)-guided stereotaxy, performed with prone positioning.

OBJECTIVE

To present technical pearls to guide the safe conduction of iMRI-guided stereotaxy and LITT while in the prone position.

METHODS

The details of the positioning and trajectories for a series of patients who underwent Clearpoint® (MRI Interventions Inc) frameless real-time MRI-guided stereotaxis using a posterior approach were reviewed.

RESULTS

In this series, 5 patients underwent selective amygdalohippocampectomy, and 2 underwent tumor biopsy/ablation while in the prone position without any complications.

CONCLUSION

Prone iMRI procedures can be performed safely even in a 60-cm MRI bore.
Intraosseous Cannulation of a Calvarial Diploic Vein for Embolization of a Symptomatic Dural Arteriovenous Fistula: A Technical Case Report
Authors: White Andrew C , Folzenlogen Zach A , Harland Tessa A , Case David E , Roark Christopher D , Kumpe David A , Seinfeld Joshua
Published: June 2019

BACKGROUND AND IMPORTANCE

Dural arteriovenous fistulas (DAVFs) may present unique challenges for treatment depending on the anatomy and pattern of venous drainage. If endovascular techniques are to be employed, the DAVF must be amenable to transvenous or transarterial therapy. When access of peripheral vasculature does not provide a straightforward path, less conventional options may be available. This case highlights a novel, technically simple, and effective approach for the treatment of a subset of DAVFs, with venous drainage through calvarial diploic veins, that would make endovascular treatment otherwise challenging or impossible.

CLINICAL PRESENTATION

We present a case of a 66-yr-old female patient who was diagnosed with a symptomatic DAVF located along the sphenoid ridge with a large intraosseous channel containing the draining vein of the fistula. This lesion was successfully treated with transcranial endovascular embolization via direct intraosseous cannulation of the calvarial diploic vein. This novel approach obviated the need for a full-thickness craniotomy, afforded only minimal bone loss, and preserved the integrity of the dura. A 3-mo follow-up angiogram confirmed complete cure of the DAVF with no residual arteriovenous shunt. At 20 mo postembolization, the patient was symptom free, with no reported neurologic deficits. Complete diagnostic work-up, treatment planning in a multidisciplinary environment, and a novel approach for endovascular embolization utilizing a hybrid operating suite played key roles in the successful implementation of this technique.

CONCLUSION

This is the first report of direct intraosseous cannulation of a calvarial diploic vein for successful transcranial endovascular embolization of a symptomatic DAVF.
Back-Running: Seeking and Hiding Fundamental Information in Order Flows*
Authors: Yang Liyan , Zhu Haoxiang
Published: June 2019

We model the strategic interaction between fundamental investors and “back-runners,” whose only information is about the past order flow of fundamental investors. Back-runners partly infer fundamental investors’ information from their order flow and exploit it in subsequent trading. Fundamental investors counteract back-runners by randomizing their orders, unless back-runners’ signals are too imprecise. Surprisingly, a higher accuracy of back-runners’ order flow information can harm back-runners and benefit fundamental investors. As an application of the model, the common practice of payment for (retail) order flow reveals information about institutional order flow and enables back-runners to earn large profits. (JEL G14, G18)
The diagnostic performance of rapid diagnostic tests and microscopy for malaria diagnosis in eastern Sudan using a nested polymerase chain reaction assay as a reference standard
Authors: Abdalla Zakya A , Rahma NourElhouda A , Hassan Elhashimi E , Abdallah Tajeldin M , Hamad Hadeel E , Omer Samia A , Adam Ishag
Published: June 2019

Background

Accurate diagnosis of malaria infection is essential for successful control and management of the disease. Both microscopy and rapid diagnostic tests (RDTs) are recommended for malaria diagnosis, however, RDTs are more commonly used. The aim of the current study was to assess the performance of microscopy and RDTs in the diagnosis of Plasmodium falciparum infection using a nested polymerase chain reaction (PCR) assay as the gold standard.

Methods

A cross-sectional study was carried out in Kassala Hospital, eastern Sudan. A total of 341 febrile participants of all ages were recruited. Blood specimens were collected and malaria testing was performed using an RDT (SD Bioline Malaria Ag Pf), microscopy and nested PCR. The sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively) of microscopy and the RDT were investigated.

Results

The prevalence of P. falciparum malaria infections in this study was 22.9%, 24.3% and 26.7% by PCR, microscopy and RDT, respectively. Compared with microscopy, the RDT had slightly higher sensitivity (80.7% vs 74.3%; p=0.442), equivalent specificity (89.3% vs 90.4%), a similar PPV (69.2% vs 69.8%) and a higher NPV (94.0% vs 92.2%).

Conclusions

The diagnostic performance of the RDT was better than that of microscopy in the diagnosis of P. falciparum malaria when nested PCR was used as the gold standard.
IX The Seventeenth Century: Part I
Authors: Baker William , Gwynn Lucy , Doelman James , James Anne , Mroz Matthew
Published: June 2019

This chapter combines what previously were Chapter IX, focusing on the earlier seventeenth century, and Chapter X, on Milton and poetry 1603–1660. Some of the content transcends historical dates and covers material from the latter half of the seventeenth century too; in other words, the long seventeenth century. It has seven sections: 1. General; 2. Bacon; 3. Browne; 4. Burton; 5. Herbert; 6. Donne; 7. Milton. Sections 1 and 2 are by William Baker; section 3 is by Lucy Gwynn and William Baker; section 4 is by William Baker; section 5 is by James Doelman; section 6 is by Anne James; section 7 is by Matthew Mroz.
X The Seventeenth Century: Part II
Authors: Netzley Ryan , Baker William , Airey Jennifer
Published: June 2019

This chapter has five sections: 1. General; 2. Other Poetry; 3. Restoration Drama Excluding Dryden; 4. Dryden; 5. Prose. Section 1 is by Ryan Netzley; section 2 is by William Baker; sections 3 and 4 are by Jennifer Airey; section 5 is by William Baker.
TheSynchytrium endobioticumAvrSen1 Triggers a Hypersensitive Response inSen1Potatoes While Natural Variants Evade Detection
Authors: van de Vossenberg Bart T. L. H. , Prodhomme Charlotte , van Arkel Gert , van Gent-Pelzer Marga P. E. , Bergervoet Marjan , Brankovics Balázs , Przetakiewicz Jarosław , Visser Richard G. F. , van der Lee Theo A. J. , Vossen Jack H.
Published: June 2019

Synchytrium endobioticum is an obligate biotrophic fungus of division Chytridiomycota. It causes potato wart disease, has a worldwide quarantine status and is included on the Health and Human Services and United States Department of Agriculture Select Agent list. S. endobioticum isolates are grouped in pathotypes based on their ability to evade host resistance in a set of differential potato varieties. Thus far, 39 pathotypes are reported. A single dominant gene (Sen1) governs pathotype 1 (D1) resistance and we anticipated that the underlying molecular model would involve a pathogen effector (AvrSen1) that is recognized by the host. The S. endobioticum-specific secretome of 14 isolates representing six different pathotypes was screened for effectors specifically present in pathotype 1 (D1) isolates but absent in others. We identified a single AvrSen1 candidate. Expression of this candidate in potato Sen1 plants showed a specific hypersensitive response (HR), which cosegregated with the Sen1 resistance in potato populations. No HR was obtained with truncated genes found in pathotypes that evaded recognition by Sen1. These findings established that our candidate gene was indeed Avrsen1. The S. endobioticum AvrSen1 is a single-copy gene and encodes a 376-amino-acid protein without predicted function or functional domains, and is the first effector gene identified in Chytridiomycota, an extremely diverse yet underrepresented basal lineage of fungi.
Weak neural signatures of spatial selective auditory attention in hearing-impaired listeners
Authors: Bonacci Lia M. , Dai Lengshi , Shinn-Cunningham Barbara G.
Published: June 2019

Spatial attention may be used to select target speech in one location while suppressing irrelevant speech in another. However, if perceptual resolution of spatial cues is weak, spatially focused attention may work poorly, leading to difficulty communicating in noisy settings. In electroencephalography (EEG), the distribution of alpha (8–14 Hz) power over parietal sensors reflects the spatial focus of attention (Banerjee et al., 2011; Foxe and Snyder, 2011). If spatial attention is degraded, however, alpha may not be modulated across parietal sensors. A previously published behavioral and EEG study found that, compared to normal-hearing (NH) listeners, hearing-impaired (HI) listeners often had higher interaural time difference (ITD) thresholds, worse performance when asked to report the content of an acoustic stream from a particular location, and weaker attentional modulation of neural responses evoked by sounds in a mixture (Dai et al., 2018). This study explored whether these same HI listeners also showed weaker alpha lateralization during the previously reported task. In NH listeners, hemispheric parietal alpha power was greater when the ipsilateral location was attended; this lateralization was stronger when competing melodies were separated by a larger spatial difference. In HI listeners, however, alpha was not lateralized across parietal sensors, consistent with a degraded ability to use spatial features to selectively attend.
Removing the hidden data dependency of DIA with predicted spectral libraries
Authors: Van Puyvelde B. , Willems S. , Gabriels R. , Daled S. , De Clerck L. , Vande Casteele S. , Staes A. , Impens F. , Deforce D. , Martens L. , Degroeve S. , Dhaenens M.
Published: June 2019

Data-Independent Acquisition (DIA) generates comprehensive yet complex mass spectrometric data, which imposes the use of data-dependent acquisition (DDA) libraries for deep peptide-centric detection. We here show that DIA can be redeemed from this dependency by combining predicted fragment intensities and retention times with narrow window DIA. This eliminates variation in library building and omits stochastic sampling, finally making the DIA workflow fully deterministic. Especially for clinical proteomics, this has the potential to facilitate inter-laboratory comparison.

Significance of the Study

Data-independent acquisition (DIA) is quickly developing into the most comprehensive strategy to analyse a sample on a mass spectrometer. Correspondingly, a wave of data analysis strategies has followed suit, improving the yield from DIA experiments with each iteration. As a result, a worldwide wave of investments in DIA is already taking place in anticipation of clinical applications. Yet, there is considerable confusion about the most useful and efficient way to handle DIA data, given the plethora of possible approaches with little regard for compatibility and complementarity. In our manuscript, we outline the currently available peptide-centric DIA data analysis strategies in a unified graphic called the DIAmond DIAgram. This leads us to an innovative and easily adoptable approach based on predicted spectral information. Most importantly, our contribution removes what is arguably the biggest bottleneck in the field: the current need for Data Dependent Acquisition (DDA) prior to DIA analysis. Fractionation, stochastic data acquisition, processing and identification all introduce bias in the library. By generating libraries through data independent, i.e. deterministic acquisition, stochastic sampling in the DIA workflow is now fully omitted. This is a crucial step towards increased standardization. Additionally, our results demonstrate that a proteome-wide predicted spectral library can surrogate an exhaustive DDA Pan-Human library that was built based on 331 prior DDA runs.
Vascularized human cortical organoids model cortical development in vivo
Authors: Shi Yingchao , Sun Le , Liu Jianwei , Zhong Suijuan , Wang Mengdi , Li Rui , Li Peng , Guo Lijie , Fang Ai , Chen Ruiguo , Ge Woo-Ping , Wu Qian , Wang Xiaoqun
Published: June 2019

Modelling the neuronal progenitor proliferation and organization processes that produce mature cortical neuron subtypes is essential for the study of human brain development and the search for potential cell therapies. To provide a vascularized and functional model of brain organoids, we demonstrated a new paradigm to generate vascularized organoids that consist of typical human cortical cell types and recapitulate the lamination of the neocortex with a vascular structure formation for over 200 days. In addition, the observation of the sEPSCs (spontaneous Excitatory Postsynaptic Potential) and sIPSCs (spontaneous Inhibitory Postsynaptic Potential) and the bidirectional electrical transmission indicated the presence of chemical and electrical synapses in the vOrganoids. More importantly, the single-cell RNA-seq analysis illustrated that the vOrganoids exhibited microenvironments to promote neurogenesis and neuronal maturation that resembled in vivo processes. The transplantation of the vOrganoids to the mouse S1 cortex showed human-mouse co-constructed functional blood vessels in the grafts that could promote the survival and integration of the transplanted cells to the host. This vOrganoid culture method could not only serve as a model to study human cortical development and to explore brain disease pathology but could also provide potential prospects for new cell therapies for neural system disorders and injury.