bluuebunny/crossref_metadata_2025 huggingface dataset:
Parent IMPACT‐III
Authors: Cushman Grace K. , Stolz Mary Gray , Shih Sharon , Blount Ronald , Otley Anthony , Talmadge Clair , Grant Amy , Reed Bonney
Published: October 2019

Objectives:

The present study aimed to validate the parent‐proxy IMPACT‐III (IMPACT‐III‐P) in a sample of youth diagnosed with inflammatory bowel disease (IBD). Parent‐proxy report measures are standard for pediatric psychosocial assessment, and the IMPACT‐III‐P will provide a more comprehensive representation of HRQOL. Reliability and validity analyses were conducted.

Methods:

Parents (N = 50) of youth 8 to 17 years with IBD reported on their child's HRQOL (IMPACT‐III‐P and PedsQL‐4.0) and depression (BASC‐2); youth reported on their HRQOL (child IMPACT‐III), pain interference (PROMIS Pain Interference), and disease symptoms; and physicians completed measures of disease activity.

Results:

Criterion validity was established as the IMPACT‐III‐P was strongly, positively associated with the PedsQL (r = 0.59, P < 0.001). Convergent validity was supported as higher IMPACT‐III‐P scores were associated with less pain interference (r = −0.41, P < 0.01) and lower depression (r = −0.41, P < 0.01). Discriminant validity was partially supported, as higher IMPACT‐III‐P scores were associated with lower child‐reported symptoms (r = −0.41, P < 0.01), but scores did not differ based on inactive, mild, or moderate/severe disease activity groups as rated by physicians. Internal consistency, parent‐child agreement, and item‐level analyses revealed strong reliability.

Conclusions:

The IMPACT‐III‐P demonstrated strong validity and reliability. Parents and children had similar reports of HRQOL, with parents rating child HRQOL slightly lower. Findings support the use of the IMPACT‐III‐P for youth 8 to 17 years old to use in accordance with the child IMPACT‐III to provide valuable information regarding HRQOL in youth with IBD.
Different Clinical Presentation of 3 Children With Familial Hemophagocytic Lymphohistiocytosis With 2 Novel Mutations
Authors: Akyol Sefika , Ozcan Alper , Sekine Takuya , Chiang Samuel C.C. , Yilmaz Ebru , Karakurkcu Musa , Patiroglu Turkan , Bryceson Yenan , Unal Ekrem
Published: October 2019

Although familial hemophagocytic lymphohistiocytosis (FHL) generally manifest with a combination of unremitting fever, hepatosplenomegaly, and pancytopenia; unusual presentations should also be taken into account. Herein, we present 3 FHL cases with 2 novel mutations with different initial presentations. The first patient bearing a homozygous truncation mutation in UNC13D (c.2650C>T.p.Gln884Ter) presented with central nervous system involvement and skin rash. The patient responded to the HLH-2004 protocol, and allogenic hematopoietic stem cell transplantation was performed from her healthy sister. The second and third patients with homozygous splice site mutation (c.430-1G>A) in STXBP2 were siblings who presented at birth with fevers, elevated aspartate aminotransferase, alanine aminotransferase, and hyperferritinemia but did not fulfill FHL criteria. The last 2 infants died despite intervention. Hematologists should be vigilant about the different presentation of FHL in children.
A Novel Approach to Electronic Nursing Documentation Education
Authors: Malane Elizabeth A. , Richardson Cynthia , Burke Kathleen G.
Published: October 2019

Health care is rapidly evolving to meet the changing needs of our increasing complex patients. Nursing practice must keep pace with these changes. Emerging information technologies such as electronic health records (EHRs) challenge nursing practice to redesign workflow. Providing nurses with effective education on how to incorporate EHR documentation is essential for safe patient care. This article describes the development of an education program that promotes accurate and more efficient nursing EHR documentation practices.
Awareness and Perceived Accuracy of Undetectable = Untransmittable: A Cross-Sectional Analysis With Implications for Treatment as Prevention Among Young Men Who Have Sex With Men
Authors: Meanley Steven , Connochie Daniel , Bonett Stephen , Flores Dalmacio D. , Bauermeister José A.
Published: October 2019

The Undetectable = Untransmittable (U=U) campaign was launched in 2016 to simultaneously reduce human immunodeficiency virus (HIV) stigma and raise awareness about treatment as prevention. This research note assesses HIV-negative young men who have sex with men's U=U awareness and perceived accuracy to inform this population's combination HIV prevention strategies.
PD-L1 Expression in Endometrial Carcinoma Cells and Intratumoral Immune Cells
Authors: Pasanen Annukka , Ahvenainen Terhi , Pellinen Teijo , Vahteristo Pia , Loukovaara Mikko , Bützow Ralf
Published: October 2019

Programmed death-ligand 1 (PD-L1) is a biomarker that may predict the response to anti-programmed death 1/PD-L1 immunotherapy. We evaluated the expression of PD-L1 in carcinoma cells (Ca) and immune cells (ICs) across histopathologic and The Cancer Genome Atlas (TCGA) molecular subgroups of endometrial carcinoma (EC). Our study included 842 patients with EC. Direct sequencing of polymerase epsilon (POLE) exonuclease domain hot spots and conventional immunohistochemistry (MLH1, PMS2, MSH2, MSH6, p53) were conducted to identify TCGA classification–based molecular subgroups of EC: POLE-mutated, mismatch repair deficient, no specific molecular profile, and p53 aberrant. Multiplex immunohistochemistry was performed to evaluate PD-L1 expression in Ca and tumor-infiltrating ICs. PD-L1 expression in Ca and in ICs was detected in 8.6% and 27.7% of the cases, respectively. A combined positive score (CPS) was ≥1% in 19.4% of the samples. PD-L1 positivity in Ca and ICs, and CPS correlated with tumor T-cell density (P<0.001). POLE-mutated and mismatch repair-deficient tumors were more likely to present PD-L1-expressing ICs, CPS positivity, and abundant tumor-infiltrating lymphocytes compared with other TCGA subgroups (P<0.001). No differences existed in Ca-PD-L1 expression (P=0.366). Within various histotypes, non-endometrioid carcinomas displayed the highest Ca-PD-L1, ICs, and CPS (P<0.03). Advanced cancers showed more frequent Ca-PD-L1 positivity (P=0.016), and CPS (P=0.029) and IC≥1% (P=0.037) positivity compared with early disease. In conclusion, PD-L1 expression profiles differ between molecular subclasses, histologic subtypes, and disease stage of EC. Prospective studies are needed to explore the predictive value of various PD-L1 scoring systems within the subgroups of EC. CPS presents methodological advantages over cell type–specific scoring systems.
Provider Consensus on Candidate Protective and Risk Factors for Adverse Psychosocial Outcomes Following Discharge From a PICU: A Modified Delphi Study*
Authors: Williams Conrad S. P. , Grossoehme Daniel H. , Forbes Michael L. , Friebert Sarah
Published: October 2019

Objectives:

Pediatric palliative care promotes interdisciplinary, family-centered care when children are faced with diagnoses threatening length and/or quality of life. A significant knowledge gap remains in how to best match pediatric palliative care resources to palliate the psychosocial impact of a PICU admission. This study was designed to identify drivers of adverse post-PICU psychosocial outcomes related to social determinants of health to inform pediatric palliative care services and improve post-PICU psychosocial outcomes.

Design:

Modified Delphi technique to develop consensus regarding social determinants of health and clinical factors affecting post-ICU psychosocial outcomes.

Setting:

All Delphi rounds were via an electronically mailed survey link.

Subjects:

First-round participants were PICU and pediatric palliative care clinicians at the study institution. Subsequent rounds invited participants from national PICU and pediatric palliative care professional online listserves.

Interventions:

None.

Measurements and Main Results:

Consensus was defined a priori as items assigned a score greater than or equal to 4 (5-point scale) by greater than75% of respondents. One-hundred twenty-six surveys were returned and scored. Social determinants of health risk factors included child protective services involvement (91%), caregiver with intellectual disability (87%), lack of friend or family support (82%), caregiver with behavioral health diagnosis (81%), teenage caregiver (79%), transportation challenges (79%), and language/cultural barrier (76%). Clinical risk factors included new home ventilator (94%), new tracheostomy (90%), greater than or equal to 3 hospitalizations in the prior 6 months (88%), and greater than or equal to 3 hospitalizations in the prior 12 months (82%). Social determinants of health protective factors included extended family support (91%), caregivers in a committed relationship (79%), and caregiver optimism (78%). Respondents reported that pediatric palliative care services had the greatest impact on caregiver satisfaction with the healthcare system (90%) and increased family involvement with state social services programs (80%).

Conclusions:

Consensus on candidate risk and protective factors for post-ICU psychosocial challenges and candidate pediatric palliative care-sensitive variables were identified. Further research is needed to operationalize and optimize a screening tool based on these consensus items and test it prospectively.
Pulmonary Artery/Vein Separation Using Single-Phase Computed Tomography
Authors: Ichikawa Shota , Yamamoto Hiroyuki , Ito Osamu , Fukunaga Masaaki
Published: October 2019

Purpose:

The purpose of this article was to verify the usefulness and feasibility of a single-phase scan for pulmonary artery/vein separation using a bolus-tracking technique and to evaluate the influence of patient characteristics on differentiation of computed tomography (CT) values between arteries and veins.

Material and Methods:

A total of 79 patients (60 male individuals and 19 female individuals, mean age 70 y) with suspected lung cancers or metastasis underwent contrast-enhanced chest CT and ultrasonic echocardiography. The CT values of the pulmonary arteries and veins were measured, and the difference in CT values was calculated. The relationships between the difference in CT values and age, weight, height, body surface area, body mass index, cardiac output, cardiac index, trigger time, trigger CT value, and pulmonary transit time were investigated using univariate linear regression analysis.

Results:

The CT values were 352.8±87.3 HU and 494.6±76.5 HU for the pulmonary arteries and veins, respectively (P<0.001). A significant but weak correlation was seen between the difference in CT values and the height (r=0.24), trigger time (r=0.35), cardiac index (r=−0.25), and pulmonary transit time (r=0.53) (P<0.05). There was no significant correlation between the difference in CT values and the remaining values.

Conclusion:

The single-phase scan protocol using a bolus-tracking technique is feasible to differentiate CT values between pulmonary arteries and veins. The influence of patient characteristics on the differentiation of CT values lacks impact. Thus, the suggested protocol may be suitable independent of these factors after further validation.
Incidence and Risk Factors of Obesity in Childhood Solid-Organ Transplant Recipients
Authors: Bondi Bianca C. , Banh Tonny M. , Vasilevska-Ristovska Jovanka , Szpindel Aliya , Chanchlani Rahul , Hebert Diane , Solomon Melinda , Dipchand Anne I. , Kim S. Joseph , Ng Vicky L. , Parekh Rulan S.
Published: October 2019

Background.

Obesity is a significant public health concern; however, the incidence post solid-organ transplantation is not well reported.

Methods.

This study determined the incidence and risk factors of obesity among pediatric solid-organ transplant recipients (heart, lung, liver, kidney, multiorgan) at The Hospital for Sick Children (2002–2011), excluding prevalent obesity. Follow-up occurred from transplantation until development of obesity, last follow-up, or end of study. Incidence of obesity was determined overall, by baseline body mass index, and organ group. Risk factors were assessed using Cox proportional-hazards regression.

Results.

Among 410 (55% male) children, median transplant age was 8.9 (interquartile range [IQR]: 1.0-14.5) years. Median follow-up time was 3.6 (IQR: 1.5-6.4) years. Incidence of obesity was 65.2 (95% confidence interval [CI]: 52.7-80.4) per 1000 person-years. Overweight recipients had a higher incidence, 190.4 (95% CI: 114.8-315.8) per 1000 person-years, than nonoverweight recipients, 56.1 (95% CI: 44.3-71.1). Cumulative incidence of obesity 5-years posttransplant was 24.1%. Kidney relative to heart recipients had the highest risk (3.13 adjusted hazard ratio [aHR]; 95% CI: 1.53-6.40) for obesity. Lung and liver recipients had similar rates to heart recipients. Those with higher baseline body mass index (z-score; 1.72 aHR; 95% CI: 1.39-2.14), overweight status (2.63 HR; 95% CI: 1.71-4.04), and younger transplant age (y; 1.18 aHR; 95% CI: 1.12-1.25) were at highest risk of obesity. Higher cumulative steroid dosage (per 10 mg/kg) was associated with increased risk of obesity after adjustment.

Conclusions.

Among all transplanted children at The Hospital for Sick Children, 25% developed obesity within 5-years posttransplant. Kidney recipients, younger children, those overweight at transplant, and those with higher cumulative steroid use (per 10 mg/kg) were at greatest risk. Early screening and intervention for obesity are important preventative strategies.
Translation and Validation of 10/66 Dementia Diagnostic Battery in Urdu in Karachi, Pakistan
Authors: Khan Qurat ul ain , Prince Martin J. , Khalid Wardah , Zulfiqar Maryam
Published: October 2019

Purpose:

The 10/66 dementia research group (DRG) diagnostic tool was devised to diagnose dementia in people with low education in low and middle-income countries. This study aimed to validate the 10/66 DRG tool in Urdu in Pakistan.

Methodology:

People older than or equal to 60 years were included: (1) With normal cognition: no/low education, high education, and depression; (2) People with mild and moderate dementia. The diagnostic and statistical manual IV-TR clinician diagnosis was used as the gold standard for dementia. The Clinician Dementia Rating scale was used to rate dementia severity. The geriatric mental status AGECAT stage I output was used to diagnose depression. The 10/66 battery was comprised of CSI-D (cognitive screening instrument for dementia), CERAD (consortium to establish a registry of Alzheimer disease), and animal naming test.

Result:

The sensitivity and specificity of CSI-D COG score for diagnosing dementia was 86.7% and 72.1%, for CSI-D DF score was 71.1% and 96.1%, for CERAD-10 word list delayed recall was 85.9% and 62.2% at a cut point of ≥5 words, and 70.3% and 97.7% for 10/66 diagnostic algorithm.

Conclusions:

The 10/66 DRG tool is a valid instrument for diagnosing dementia in the Urdu-speaking population, including with low education and depression, in Pakistan.
Overview of EEG Montages and Principles of Localization
Authors: Acharya Jayant N. , Acharya Vinita J.
Published: October 2019

Montages are logical, orderly arrangements of electroencephalographic derivations or channels that are created to display activity over the entire head and to provide lateralizing and localizing information. Most often, bipolar and referential montages are used for routine electroencephalographic recordings. Common average and Laplacian montages can also be helpful in some situations. Because each type of montage has certain strengths and limitations, the ACNS guidelines recommend the use of multiple classes of montages for each electroencephalographic recording. A variety of factors need to be considered for localization by scalp electroencephalogram, but in clinical practice, a three-step approach can be used to localize an interictal epileptiform discharge by visual inspection using a standard set of scalp electrodes and conventional montages. The ACNS guideline provides a number of standard and suggested montages, but, depending on the clinical situation, additional montages can be designed using the electrodes within the 10-20 system or by placing additional electrodes.
Montages for Noninvasive EEG Recording
Authors: Kutluay Ekrem , Kalamangalam Giridhar P.
Published: October 2019

Identifying the localization, distribution, and polarity of waveforms are the prime goals of clinical scalp EEG analysis. Appropriate choices of bipolar and referential montages are keys to emphasizing the diagnostic features of interest, and demand some understanding of the spatiotemporal physical behavior of the underlying neuronal generators. Several examples drawn from canonical epilepsy syndromes are used to illustrate this general message.
Accurate and efficient discretizations for stochastic models providing near agent-based spatial resolution at low computational cost
Authors: Fadai Nabil T. , Baker Ruth E. , Simpson Matthew J.
Published: October 2019

Understanding how cells proliferate, migrate and die in various environments is essential in determining how organisms develop and repair themselves. Continuum mathematical models, such as the logistic equation and the Fisher–Kolmogorov equation, can describe the global characteristics observed in commonly used cell biology assays, such as proliferation and scratch assays. However, these continuum models do not account for single-cell-level mechanics observed in high-throughput experiments. Mathematical modelling frameworks that represent individual cells, often called agent-based models, can successfully describe key single-cell-level features of these assays but are computationally infeasible when dealing with large populations. In this work, we propose an agent-based model with crowding effects that is computationally efficient and matches the logistic and Fisher–Kolmogorov equations in parameter regimes relevant to proliferation and scratch assays, respectively. This stochastic agent-based model allows multiple agents to be contained within compartments on an underlying lattice, thereby reducing the computational storage compared to existing agent-based models that allow one agent per site only. We propose a systematic method to determine a suitable compartment size. Implementing this compartment-based model with this compartment size provides a balance between computational storage, local resolution of agent behaviour and agreement with classical continuum descriptions.
Trabecular bone architecture in the stylopod epiphyses of mustelids (Mammalia, Carnivora)
Authors: Amson E. , Kilbourne B. M.
Published: October 2019

Mustelidae, a carnivoran clade that includes for instance weasels, badgers, otters and martens, has undergone several evolutionary transitions of lifestyle, resulting in specializations for fossorial, natatorial and scansorial locomotion, in addition to more generalized species. The family is therefore regarded as offering an adequate framework for morpho-functional analyses. However, the architecture of the epiphyseal trabecular bone, which is argued to be particularly responsive to the biomechanical environment, has never been studied. Here, we quantify trabecular bone parameters of the proximal and distal epiphyses of the humerus and femur in 29 species of mustelids and assess the differences of these parameters among groups defined
a priori
based on the aforementioned locomotor types. The parameters are assessed in a phylogenetic framework, taking into account the potential effect on an individual's body mass. The range of variation described by the acquired parameters is relatively restricted when compared to that of other clades. Generalists, however, are featuring a wider range of variation than the other types. While clear discrimination of locomotor types is difficult, some differences were highlighted by our analysis, such as a greater bone fraction associated with the natatorial taxa, which we discuss in a functional context.
Formation of neural networks with structural and functional features consistent with small-world network topology on surface-grafted polymer particles
Authors: Valderhaug Vibeke Devold , Glomm Wilhelm Robert , Sandru Eugenia Mariana , Yasuda Masahiro , Sandvig Axel , Sandvig Ioanna
Published: October 2019

In vitro
electrophysiological investigation of neural activity at a network level holds tremendous potential for elucidating underlying features of brain function (and dysfunction). In standard neural network modelling systems, however, the fundamental three-dimensional (3D) character of the brain is a largely disregarded feature. This widely applied neuroscientific strategy affects several aspects of the structure–function relationships of the resulting networks, altering network connectivity and topology, ultimately reducing the translatability of the results obtained. As these model systems increase in popularity, it becomes imperative that they capture, as accurately as possible, fundamental features of neural networks in the brain, such as small-worldness. In this report, we combine
in vitro
neural cell culture with a biologically compatible scaffolding substrate, surface-grafted polymer particles (PPs), to develop neural networks with 3D topology. Furthermore, we investigate their electrophysiological network activity through the use of 3D multielectrode arrays. The resulting neural network activity shows emergent behaviour consistent with maturing neural networks capable of performing computations, i.e. activity patterns suggestive of both information segregation (desynchronized single spikes and local bursts) and information integration (network spikes). Importantly, we demonstrate that the resulting PP-structured neural networks show both structural and functional features consistent with small-world network topology.
Investigating face and house discrimination at foveal to parafoveal locations reveals category-specific characteristics
Authors: Kreichman Olga , Bonneh Yoram , Gilaie-Dotan Sharon
Published: October 2019

Since perceptual and neural face sensitivity is associated with a foveal bias, and neural place sensitivity is associated with a peripheral bias (integration over space), we hypothesized that face perception ability will decline more with eccentricity than place perception ability. We also hypothesized that face perception ability may show an upper visual field (UVF) bias due to the proximity of face-related regions to UVF retinotopic representations, and a left visual field (LeVF) bias due to earlier reports suggesting right hemisphere dominance for faces. Participants performed foveal and parafoveal face and house discrimination tasks for upright or inverted stimuli (≤ 4°) while their eye movements were monitored. Low-level visual tasks were also measured. The eccentricity-related accuracy reductions were evident for all categories. Through detailed analyses we found (i) a robust face inversion effect across the parafovea, while for houses an opposite effect was found, (ii) higher eccentricity-related sensitivity for face performance than for house performance (via inverted vs. upright within-category eccentricity-driven reductions), (iii) within-category but not across-category performance associations across eccentricities, and (iv) no hemifield biases. Our central to parafoveal investigations suggest that high-level vision processing may be reflected in behavioural performance.
Reconstruction of fish allergenicity from the content and structural traits of the component β-parvalbumin isoforms
Authors: Pérez-Tavarez Raquel , Carrera Mónica , Pedrosa María , Quirce Santiago , Rodriguez-Perez Rosa , Gasset María
Published: October 2019

Most fish-allergic patients have anti-β-parvalbumin (β-PV) immunoglobulin E (IgE), which cross-reacts among fish species with variable clinical effects. Although the β-PV load is considered a determinant for allergenicity, fish species express distinct β-PV isoforms with unknown pathogenic contributions. To identify the role various parameters play in allergenicity, we have takenGadus morhuaandScomber japonicusmodels, determined their β-PV isoform composition and analyzed the interaction of the IgE from fish-allergic patient sera with these different conformations. We found that each fish species contains a major and a minor isoform, with the total PV content four times higher inGadus morhuathan inScomber japonicus. The isoforms showing the best IgE recognition displayed protease-sensitive globular folds, and if forming amyloids, they were not immunoreactive. Of the isoforms displaying stable globular folds, one was not recognized by IgE under any of the conditions, and the other formed highly immunoreactive amyloids. The results showed thatGadus morhuamuscles are equipped with an isoform combination and content that ensures the IgE recognition of all PV folds, whereas the allergenic load ofScomber japonicusis under the control of proteolysis. We conclude that the consideration of isoform properties and content may improve the explanation of fish species allergenicity differences.
Metabolic complementarity between a brown alga and associated cultivable bacteria provide indications of beneficial interactions
Authors: Burgunter-Delamare Bertille , KleinJan Hetty , Frioux Clémence , Fremy Enora , Wagner Margot , Corre Erwan , Salver Alicia Le , Leroux Cédric , Leblanc Catherine , Boyen Catherine , Siegel Anne , Dittami Simon M.
Published: October 2019

Brown algae are key components of marine ecosystems and live in association with bacteria that are essential for their growth and development. Ectocarpus siliculosus is a genetic and genomic model for brown algae. Here we use this model to start disentangling the complex interactions that may occur between the algal host and its associated bacteria. We report the genome-sequencing of 10 alga-associated bacteria and the genome-based reconstruction of their metabolic networks. The predicted metabolic capacities were then used to identify metabolic complementarities between the algal host and the bacteria, highlighting a range of potentially beneficial metabolite exchanges between them. These putative exchanges allowed us to predict consortia consisting of a subset of these ten bacteria that would best complement the algal metabolism. Finally, co-culture experiments were set up with a subset of these consortia to monitor algal growth as well as the presence of key algal metabolites. Although we did not fully control but only modify bacterial communities in our experiments, our data demonstrated a significant increase in algal growth in cultures inoculated with the selected consortia. In several cases, we also detected, in algal extracts, the presence of key metabolites predicted to become producible via an exchange of metabolites between the alga and the microbiome. Thus, although further methodological developments will be necessary to better control and understand microbial interactions in Ectocarpus, our data suggest that metabolic complementarity is a good indicator of beneficial metabolite exchanges in holobiont.
DNA fingerprinting: an effective tool for taxonomic identification of processed precious corals
Authors: Lendvay Bertalan , Cartier Laurent E. , Gysi Mario , Meyer Joana B. , Krzemnicki Michael S. , Kratzer Adelgunde , Morf Nadja V.
Published: October 2019

Precious coral species have been used to produce jewelry and ornaments since antiquity. Due to the high prices at which corals are traded, coral beds have been heavily fished. Hence, fishing and international trade regulations were put in place. However, poaching remains extensive and mislabeling of products is common. To this date, the control of precious coral exploitation and enforcement of trade rules have been largely impaired by the fact that species of processed coral skeletons can be extremely difficult to distinguish even for trained experts.

Here, we developed methods to use DNA recovered from worked precious coral skeletons to identify their species. We evaluated purity and quantity of DNA extracted using five different techniques. Then, a minimally invasive sampling protocol was tested, which allowed genetic analysis without compromising the value of the worked coral objects.

We found extraction of pure DNA possible in all cases using 100 mg skeletal material and over half of the cases when using “quasi non-destructive” sampling with sampled material amount as low as 2.3 mg. Sequence data of the recovered DNA gave a strong indication that the range of precious coral species present in the trade is broader than previously anticipated.
The GMD-biplot and its application to microbiome data
Authors: Wang Yue , Randolph Timothy W , Shojaie Ali , Ma Jing
Published: October 2019

Exploratory analysis of human microbiome data is often based on dimension-reduced graphical displays derived from similarities based on non-Euclidean distances, such as UniFrac or Bray-Curtis. However, a display of this type, often referred to as the principal coordinate analysis (PCoA) plot, does not reveal which taxa are related to the observed clustering because the configuration of samples is not based on a coordinate system in which both the samples and variables can be represented. The reason is that the PCoA plot is based on the eigen-decomposition of a similarity matrix and not the singular value decomposition (SVD) of the sample-by-abundance matrix. We propose a novel biplot that is based on an extension of the SVD, called the generalized matrix decomposition (GMD), which involves an arbitrary matrix of similarities and the original matrix of variable measures, such as taxon abundances. As in a traditional biplot, points represent the samples and arrows represent the variables. The proposed GMD-biplot is illustrated by analyzing multiple real and simulated data sets which demonstrate that the GMD-biplot provides improved clustering capability and a more meaningful relationship between the arrows and the points.
Nonlinear relationship between multimodal adrenergic responses and local dendritic activity in primary sensory cortices
Authors: Deitcher Yair , Leibner Yonatan , Kutzkel Sara , Zylbermann Neta , London Michael
Published: October 2019

The axonal projections of the adrenergic system to the neocortex, originating from the locus coeruleus (LC), form a dense network. These axons release the neuromodulator norepinephrine (NE) which is involved in many cognitive functions such as attention, arousal, and working memory. Using two-photon Ca2+ imaging of NE axons in the cortex of awake mice, we investigated what drives their phasic activity. We discovered that NE axons in the primary somatosensory cortex responded robustly and reliably to somatosensory stimulation. Surprisingly, the same axons also responded to stimuli of other modalities (auditory and visual). Similar responses to all three modalities were observed in the primary visual cortex as well. These results indicate that phasic responses of NE axons to sensory stimuli provide a robust multimodal signal. However, despite the robustness, we also noticed consistent variations in the data. For example, responses to whisker stimulations were larger than to auditory and visual stimulations in both the barrel and the visual cortices. To test whether the variations in NE axonal responses can carry behaviorally meaningful information, we trained mice in an associative auditory fear conditioning paradigm. We found that following conditioning the response of NE axons increased only for CS+, namely the signal undergoes experience-dependent plasticity and is specific to meaningful sounds. To test if variations in NE axonal responses can differentially affect the cortical microcircuit, we used dual-color two-photon Ca2+ imaging and studied the relationship between the activity of NE axons and local dendrites. We found dendritic Ca2+ signals in barrel cortex in response to auditory stimuli, but these responses were variable and unreliable. Strikingly, the probability of such dendritic signals increased nonlinearly with the Ca2+ signals of NE axons. Our results demonstrate that the phasic activity of the noradrenergic neurons may serve as a robust multimodal and plastic signal in sensory cortices. Furthermore, the variations in the NE axonal activity carry behaviorally meaningful signals and can predict the probability of local dendritic Ca2+ events.
Diagnosis of Centrocestus formosanus Infection in Zebrafish (Danio rerio): A Window on a New Globalization-Derived Invasive Parasite
Authors: Pace Antonino , Dipineto Ludovico , Aceto Serena , Censullo Maria Concetta , Valoroso Maria Carmen , Varriale Lorena , Rinaldi Laura , Menna Lucia Francesca , Fioretti Alessandro , Borrelli Luca
Published: October 2019

Centrocestus formosanusis a digenetic trematode with a complex life cycle, involving invertebrate and vertebrate hosts, humans included. In particular, it causes gill lesions and mortality in freshwater fish species, and gastrointestinal symptoms in infected humans. Here,we describe the occurrence of C. formosanus infection in zebrafish imported in Italy. Gill arches of 30 zebrafish were examined for the presence of encysted metacercariae under a stereomicroscope, and processed through molecular analyses targeting the ribosomal Internal Transcribed Sequence 2 (ITS2) using species-specific primers of C. formosanus. Encysted metacercariae were found on the gills of 20/30 zebrafish and all were identified as C. formosanus.

Despite C. formosanus distribution was originally restricted to Asia, it has been subsequently reported in new countries, revealing itself as an invasive species, and raising important concerns for biodiversity, economy, animal and public health. Given the crucial role likely played by the ornamental fish industry in the spreading of this parasite, there is an urgent need for control measures to prevent the introduction and establishment of C. formosanus in non-endemic areas, Europe included. An adequate surveillance and health-monitoring program should be conducted in the development of microbiological and epidemiological approaches to diagnose and face these new globalization-derived invasive species.
A Sensitive Yellow Fever Virus Entry Reporter Identifies Valosin-Containing Protein (VCP/p97) as an Essential Host Factor for Flavivirus Uncoating
Authors: Ramanathan Harish N. , Zhang Shuo , Douam Florian , Chang Jinhong , Yang Priscilla L. , Ploss Alexander , Lindenbach Brett D.
Published: October 2019

While the basic mechanisms of flavivirus entry and fusion are understood, little is known about the post-fusion events that precede RNA replication, such as nucleocapsid disassembly. We describe here a sensitive, conditionally replication-defective yellow fever virus (YFV) entry reporter, YFVΔSK/Nluc, to quantitively monitor the translation of incoming, virus particle-delivered genomes. We validated that YFVΔSK/Nluc gene expression can be neutralized by YFV-specific antisera and requires known flavivirus entry pathways, including clathrin- and dynamin-mediated endocytosis, endosomal acidification, YFV E glycoprotein-mediated fusion, and cellular LY6E expression; however, as expected, gene expression from the defective reporter virus was insensitive to a small molecule inhibitor of YFV RNA replication. YFVΔSK/Nluc gene expression was also shown to require cellular ubiquitylation, consistent with recent findings that dengue virus capsid protein must be ubiquitylated in order for nucleocapsid uncoating to occur, as well as valosin-containing protein (VCP)/p97, a cellular ATPase that unfolds and extracts ubiquitylated client proteins from large macromolecular complexes. RNA transfection and washout experiments showed that VCP/p97 functions at a post-fusion, pre-translation step in YFV entry. Together, these data support a critical role for VCP/p97 in the disassembly of incoming flavivirus nucleocapsids during a post-fusion step in virus entry.

IMPORTANCE

Flaviviruses are an important group of RNA viruses that cause significant human disease. The mechanisms by which flavivirus nucleocapsids are disassembled during virus entry remain unclear. Here we show that the yellow fever virus nucleocapsid disassembly requires the cellular protein-disaggregating enzyme valosin-containing protein, also known as p97.
Clathrin light chain diversity regulates membrane deformation in vitro and synaptic vesicle formation in vivo
Authors: Redlingshöfer Lisa , McLeod Faye , Chen Yu , Camus Marine D. , Burden Jemima J. , Palomer Ernest , Briant Kit , Dannhauser Philip N. , Salinas Patricia C. , Brodsky Frances M.
Published: October 2019

Clathrin light chain (CLC) subunits in vertebrates are encoded by paralogous genesCLTAandCLTBand both gene products are alternatively spliced in neurons. To understand how this CLC diversity influences neuronal clathrin function, we characterised the biophysical properties of clathrin comprising individual CLC variants for correlation with neuronal phenotypes of mice lacking either CLC-encoding gene. CLC splice variants differentially influenced clathrin knee conformation within assemblies, and clathrin with neuronal CLC mixtures was more effective in membrane deformation than clathrin with single neuronal isoforms nCLCa or nCLCb. Correspondingly, electrophysiological recordings revealed that neurons from mice lacking nCLCa or nCLCb were both defective in synaptic vesicle replenishment. Mice with only nCLCb had a reduced synaptic vesicle pool and impaired neurotransmission compared to wild-type mice, while nCLCa-only mice had increased synaptic vesicle numbers, restoring normal neurotransmission. These findings highlight differences between the CLC isoforms and show that isoform mixing influences tissue-specific clathrin activity in neurons, which requires their functional balance.

SIGNIFICANCE STATEMENT

This study reveals that diversity of clathrin light chain (CLC) subunits alters clathrin properties and demonstrates that the two neuronal CLC subunits work together for optimal clathrin function in synaptic vesicle formation. Our findings establish a role for CLC diversity in synaptic transmission and illustrate how CLC variability expands the complexity of clathrin to serve tissue-specific functions.
Phenotype-based screening of synthetic cannabinoids in a Dravet Syndrome zebrafish model
Authors: Griffin Aliesha , Anvar Mana , Hamling Kyla , Baraban Scott C.
Published: October 2019

Dravet syndrome (DS) is a catastrophic epilepsy of childhood, characterized by cognitive impairment, severe seizures and increased risk for sudden unexplained death in epilepsy (SUDEP). Although refractory to conventional antiepileptic drugs, emerging preclinical and clinical evidence suggests that modulation of the endocanniboid system could be therapeutic in these patients. Here we used a validated zebrafish model of DS, scn1lab homozygous mutants, to screen a commercially available library containing 370 synthetic cannabinoid (SC) compounds for compounds effective in reducing spontaneous seizures. Primary phenotype-based screening was performed using a locomotion-based assay in 96-well plates, and a secondary local field potential recording assay was then used to confirm suppression of electrographic epileptiform events. Identified SCs with anti-seizure activity, in both assays, included five SCs structurally classified as indole-based cannabinoids: JWH 018 N-(5-chloropentyl) analog, JWH 018 N-(2-methylbutyl) isomer, 5-fluoro PB-22 5-hydroxyisoquinoline isomer, 5-fluoro ADBICA, and AB-FUBINACA 3-fluorobenzyl isomer. Our approach demonstrates that two-stage phenotype-based screening in a zebrafish model of DS successfully identifies synthetic cannabinoids with anti-seizure activity, and supports further investigation of SCs for refractory epilepsies.
Dynamics of microRNA expression during mouse prenatal development
Authors: Rahmanian Sorena , Murad Rabi , Breschi Alessandra , Zeng Weihua , Mackiewicz Mark , Williams Brian , Davis Carrie A. , Roberts Brian , Meadows Sarah , Moore Dianna , Trout Diane , Zaleski Chris , Dobin Alex , Sei Lei-Hoon , Drenkow Jorg , Scavelli Alex , Gingeras Thomas R. , Wold Barbara J. , Myers Richard M. , Guigó Roderic , Mortazavi Ali
Published: October 2019

MicroRNAs (miRNAs) play a critical role as posttranscriptional regulators of gene expression. The ENCODE Project profiled the expression of miRNAs in an extensive set of organs during a time-course of mouse embryonic development and captured the expression dynamics of 785 miRNAs. We found distinct organ-specific and developmental stage–specific miRNA expression clusters, with an overall pattern of increasing organ-specific expression as embryonic development proceeds. Comparative analysis of conserved miRNAs in mouse and human revealed stronger clustering of expression patterns by organ type rather than by species. An analysis of messenger RNA expression clusters compared with miRNA expression clusters identifies the potential role of specific miRNA expression clusters in suppressing the expression of mRNAs specific to other developmental programs in the organ in which these miRNAs are expressed during embryonic development. Our results provide the most comprehensive time-course of miRNA expression as part of an integrated ENCODE reference data set for mouse embryonic development.
Dramatic response of metastatic cutaneous angiosarcoma to an immune checkpoint inhibitor in a patient with xeroderma pigmentosum: whole-genome sequencing aids treatment decision in end-stage disease
Authors: Momen Sophie , Fassihi Hiva , Davies Helen R. , Nikolaou Christos , Degasperi Andrea , Stefanato Catherine M. , Dias Joao M. L. , Dasgupta Dhruba , Craythorne Emma , Sarkany Robert , Papa Sophie , Nik-Zainal Serena
Published: October 2019

“Mutational signatures” are patterns of mutations that report DNA damage and subsequent repair processes that have occurred. Whole-genome sequencing (WGS) can provide additional information to standard diagnostic techniques and can identify therapeutic targets. A 32-yr-old male with xeroderma pigmentosum developed metastatic angiosarcoma that was unresponsive to three lines of conventional sarcoma therapies. WGS was performed on his primary cancer revealing a hypermutated tumor, including clonal ultraviolet radiation-induced mutational patterns (Signature 7) and subclonal signatures of mutated DNA polymerase epsilon (POLE) (Signature 10). These signatures are associated with response to immune checkpoint blockade. Immunohistochemistry confirmed high PD-L1 expression in metastatic deposits. The anti-PD-1 monoclonal antibody pembrolizumab was commenced off-label given the POLE mutation and high mutational load. After four cycles, there was a significant reduction in his disease with almost complete resolution of the metastatic deposits. This case highlights the importance of WGS in the analysis, interpretation, and treatment of cancers. We anticipate that as WGS becomes integral to the cancer diagnostic pathway, treatments will be stratified to the individual based on their unique genomic and/or transcriptomic profile, enhancing classical approaches of histologically driven treatment decisions.
Competences in higher education tourism internships
Authors: Ferreras-Garcia Raquel , Sales-Zaguirre Jordi , Serradell-López Enric
Published: October 2019

Purpose

The purpose of this paper is to examine the level of correspondence between the academic training received by students and the demands of the job market. This was achieved by analysing the competences that are developed in internships to provide useful information for universities, students and tourism companies.

Design/methodology/approach

A quantitative analysis was carried out using questionnaires administered to the supervisors of students on curricular internships. The level of tourism competences of students on the bachelor degree in Tourism and Hospitality Management at the School of Tourism and Hospitality Management Sant Ignasi was assessed. A descriptive analysis and comparisons of means were carried out to investigate differences in competences between students undertaking internships, according to the hotel department and category.

Findings

The results of the study indicate that students undertaking internships improve their competences. Whether they undertake internships in one department or another does not affect the level of achievement of most competences. However, the category of a hotel does influence the level of development of the acquired competences.

Research limitations/implications

A questionnaire should be administered to students on their perceptions of the achievement of competences, as this could be compared with the supervisors’ perceptions.

Practical implications

The study generates extremely valuable information for companies, universities and students, as it reveals which competences are attained and to what extent. Based on these results, universities can adapt their training activities and the hotel industry will have information on learning processes during internships.

Originality/value

The analysis provides an innovative research, a real assessment by employers of the competences attained. It also identifies the need for more research on the subject related to employers’ perceptions of the level of competences that students develop in the workplace.
The embodiment of social capital at individual and communal levels
Authors: Au Anson
Published: October 2019

Purpose

The purpose of this paper is to review the study of social capital focused on the level at which it is embodied, cross-comparing two prominent camps that have emerged in the social capital literature: a communal level and an individual level.

Design/methodology/approach

This paper reviews the intersections and departures between communal level and individual level conceptualizations of social capital according to the social dynamics of action within social exchanges that they stimulate, the processes by which social capital is activated/mobilized and the rewards they yield, and their linkages to inequality through network diversity.

Findings

This paper articulates new directions for future research in social capital: more analytical precision for studying returns to social capital; more efforts to transcend the individual-communal divide; the depreciation of social capital or tie decay; and recognizing the importance of ties whose value does not come from the ability to provide instrumental gain, but just from their very existence.

Originality/value

Social capital has informed many influential agendas in the social sciences, but the sheer volume of which has largely gone unscoped. This paper reviews this literature to provide an accessible introduction to social capital, organized by social processes foundational to sociology and a novel contribution to the literature by articulating new directions for future research in the area.