bluuebunny/crossref_metadata_2025 huggingface dataset:
Plateau pikas (Ochotona curzoniae) at low densities have no destructive effect on winter pasture in alpine meadows
Authors: Wei W. R. , He J. D. , Zheng Q. Y.
Published: April 2020

The plateau pika (Ochotona curzoniae) is a common small mammal species present in the alpine meadow ecosystem on the Qinghai-Tibetan Plateau (QTP), and is regarded as a pest in alpine meadows when population density exceeds a certain threshold. However, whether pikas with a low population density have a detrimental effect on alpine meadows in winter pasture is unknown. Vegetation and soil were sampled in eight individual pika patchy home ranges and eight control areas, and we found vegetation and soil properties showed different trends in the pika home ranges. Plateau pika activity significantly increased the below-ground biomass, soil pH and total potassium, but had no significant effect on the plant species richness or diversity, soil moisture, NH4-N, NO3-N, total phosphorus, available phosphorus and soil organic content. However, plateau pika activity reduced some vegetation and soil properties (e.g. vegetation cover, vegetation height, aboveground biomass, graminoids, soil bulk density and available potassium). These results imply that pika activity may improve some soil nutrients but have no destructive effect on winter pasture at a low population density.
The complexity of human computation via a concrete model with an application to passwords
Authors: Blum Manuel , Vempala Santosh
Published: April 2020

Significance

This work presents a concrete, mathematically precise model of what humans can compute in their heads. It thereby provides a method to probe the limits of human computation (can humans generate numbers that look random to a powerful computer?) as well as to design efficient humanly computable mental algorithms for everyday tasks, such as generating passwords and making real-time decisions.
Coastal heritage, global climate change, public engagement, and citizen science
Authors: Dawson Tom , Hambly Joanna , Kelley Alice , Lees William , Miller Sarah
Published: April 2020

Climate change is threatening an uncalculated number of archaeological sites globally, totaling perhaps hundreds of thousands of culturally and paleoenvironmentally significant resources. As with all archaeological sites, they provide evidence of humanity’s past and help us understand our place in the present world. Coastal sites, clustered at the water’s edge, are already experiencing some of the most dramatic damage due to anthropogenic climate change, and the situation is predicted to worsen in the future. In the face of catastrophic loss, organizations around the world are developing new ways of working with this threatened coastal resource. This paper uses three examples from Scotland, Florida, and Maine to highlight how new partnerships and citizen science approaches are building communities of practice to better manage threatened coastal heritage. It compares methods on either side of the Atlantic and highlights challenges and solutions. The approaches are applicable to the increasing number of heritage sites everywhere at risk from climate change; the study of coastal sites thus helps society prepare for climate change impacts to heritage worldwide.
Leveraging legacy archaeological collections as proxies for climate and environmental research
Authors: St. Amand Frankie , Childs S. Terry , Reitz Elizabeth J. , Heller Sky , Newsom Bonnie , Rick Torben C. , Sandweiss Daniel H. , Wheeler Ryan
Published: April 2020

Understanding the causes and consequences of previous climate changes is essential for testing present-day climate models and projections. Archaeological sites are paleoenvironmental archives containing unique ecological baselines with data on paleoclimate transformations at a human timescale. Anthropogenic and nonanthropogenic forces have destroyed many sites, and others are under immediate threat. In the face of this loss, previously excavated collections from these sites—referred to as legacy collections—offer a source of climate and other paleoenvironmental information that may no longer exist elsewhere. Here, we 1) review obstacles to systematically using data from legacy archaeological collections, such as inconsistent or unreported field methods, inadequate records, unsatisfactory curation, and insufficient public knowledge of relevant collections; 2) suggest best practices for integrating archaeological data into climate and environmental research; and 3) summarize several studies to demonstrate the benefits and challenges of using legacy collections as archives of local and regional environmental proxies. Data from archaeological legacy collections contribute regional ecological baselines as well as serve to correct shifting baselines. They also enable regional climate reconstructions at various timescales and corroborate or refine radiocarbon dates. Such uses of legacy collections raise ethical concerns regarding ownership of and responsibility for cultural resources and highlight the importance of Indigenous involvement in planning and executing fieldwork and stewardship of cultural heritage. Finally, we discuss methodologies, practices, and policies pertaining to archaeological legacy collections and support calls for discipline-wide shifts in collections management to ensure their long-term utility in multidisciplinary research and public engagement.
Archaeology, environmental justice, and climate change on islands of the Caribbean and southwestern Indian Ocean
Authors: Douglass Kristina , Cooper Jago
Published: April 2020

Climate change impacts island communities all over the world. Sea-level rise, an increase in the frequency and intensity of severe weather events, and changes in distribution and health of marine organisms are among the most significant processes affecting island communities worldwide. On islands of the Caribbean and southwestern Indian Ocean (SWIO), however, today’s climate change impacts are magnified by historical environmental injustice and colonial legacies, which have heightened the vulnerability of human and other biotic communities. For some islands, archaeological and paleoecological research offers an important record of precolonial climate change and its interplay with human lives and landscapes. The archaeological record suggests strategies and mechanisms that can inform discussions of resilience in the face of climate change. We detail climate-related challenges facing island Caribbean and SWIO communities using archaeological and paleoecological evidence for past climate change and human response and argue that these cannot be successfully addressed without an understanding of the processes that have, over time, disrupted livelihoods, reshaped land- and seascapes, threatened intergenerational ecological knowledge transfer, and led to increased inequality and climate vulnerability.
The T1D-associated lncRNA
Lnc13
modulates human pancreatic β cell inflammation by allele-specific stabilization of
STAT1
mRNA
Authors: Gonzalez-Moro Itziar , Olazagoitia-Garmendia Ane , Colli Maikel L. , Cobo-Vuilleumier Nadia , Postler Thomas S. , Marselli Lorella , Marchetti Piero , Ghosh Sankar , Gauthier Benoit R. , Eizirik Decio L. , Castellanos-Rubio Ainara , Santin Izortze
Published: April 2020

Significance

The mechanisms by which autoimmunity is triggered/amplified in T1D remain to be clarified, and the lack of this basic understanding hampers efforts to prevent or arrest the disease. Testing the hypothesis that T1D-associated genetic variants in lncRNAs affect important pathways that modify inflammation and pancreatic β-cell survival will increase our understanding of T1D pathogenesis. In the present paper, we describe a molecular mechanism by which the T1D-associated lncRNA
Lnc13
regulates pancreatic β-cell inflammation. These findings provide information on the molecular mechanisms by which disease-associated SNPs in lncRNAs influence disease pathogenesis and open the door for the development of novel diagnostic and therapeutic approaches based on lncRNA targeting.
Dynamic coupling of whole-brain neuronal and neurotransmitter systems
Authors: Kringelbach Morten L. , Cruzat Josephine , Cabral Joana , Knudsen Gitte Moos , Carhart-Harris Robin , Whybrow Peter C. , Logothetis Nikos K. , Deco Gustavo
Published: April 2020

Significance

In a technical tour de force, we have created a framework demonstrating the underlying fundamental principles of bidirectional coupling of neuronal and neurotransmitter dynamical systems. Specifically, in the present study, we combined multimodal neuroimaging data to causally explain the functional effects of specific serotoninergic receptor (5-HT
2A
R) stimulation with psilocybin in healthy humans. Longer term, this could provide a better understanding of why psilocybin is showing considerable promise as a therapeutic intervention for neuropsychiatric disorders including depression, anxiety, and addiction.
Exploring the longitudinal development of grammatical complexity in the disciplinary writing of L2-English university
students
Authors: Biber Douglas , Reppen Randi , Staples Shelley , Egbert Jesse
Published: April 2020

The present paper employs a corpus-based approach to track the longitudinal language development of university
students. Compared to many other longitudinal studies, the present study tracks development over a relatively long period of time
(two years) for a relatively large group of students (N = 22). However, the most important difference from
previous research is that the study explores the linguistic characteristics of disciplinary writing, across levels of education
and academic disciplines, investigating the writing tasks required for disciplinary content courses over two years of university
education. We focus on grammatical complexity features associated with the hypothesized stages of development proposed in Biber et al. (2011). Methodologically, the study proposes research designs and
statistical approaches that permit investigation of longitudinal development in an unbalanced corpus of natural texts. And
linguistically, the results generally support the hypothesized stages of development, documenting a decline in the use of
dependent clause complexity features and an increase in the use of phrasal complexity features. As such, the study adds to the
growing body of research that emphasizes the importance of phrasal complexity in the development of academic writing.
Internet memes as multilayered re-contextualization vehicles in lay-political online
discourse
Authors: Kirner-Ludwig Monika
Published: April 2020

It is well established that the internet meme has come to represent a highly creative discursive device used to
“facilitate the […] communication of one’s own political beliefs, attitudes and orientations” (Ross and Rivers 2017: 1). Although internet memes and political internet memes in particular have been addressed to
many communicative situations such as participatory culture (e.g., Jenkins 2006; Shifman 2014; Theocharis 2015), one aspect
that has not been paid enough attention to concerns the forms in which users refer to individual political figures and events in
political memes. This being said, the present paper focuses on referring strategies (see Kirner-Ludwig and Zimmermann 2015; Kirner-Ludwig 2020) as employed in
political internet memes on Reddit, including direct and indirect quotes, citations and allusions. A specific focus is going to be
on such political internet memes that employ pop cultural and telecinematic reference points and recontextualize them from their
original into new target contexts (see Bublitz 2015; Gruber 2019). As shall be shown, practices such as combining constructed speech elements into
recontextualized elements in political internet memes create multiple intertextual references that may enhance visibility,
saliency and, thus, the ‘lifetime’ of a political meme.
COVID-19 and emerging viral infections: The case for interferon lambda
Authors: Prokunina-Olsson Ludmila , Alphonse Noémie , Dickenson Ruth E. , Durbin Joan E. , Glenn Jeffrey S. , Hartmann Rune , Kotenko Sergei V. , Lazear Helen M. , O’Brien Thomas R. , Odendall Charlotte , Onabajo Olusegun O. , Piontkivska Helen , Santer Deanna M. , Reich Nancy C. , Wack Andreas , Zanoni Ivan
Published: April 2020

With the first reports on coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the scientific community working in the field of type III IFNs (IFN-λ) realized that this class of IFNs could play an important role in this and other emerging viral infections. In this Viewpoint, we present our opinion on the benefits and potential limitations of using IFN-λ to prevent, limit, and treat these dangerous viral infections.
Lower Ca2+ enhances the K+-induced force depression in normal and HyperKPP mouse muscles
Authors: Uwera Francine , Ammar Tarek , McRae Callum , Hayward Lawrence J. , Renaud Jean-Marc
Published: April 2020

Hyperkalemic periodic paralysis (HyperKPP) manifests as stiffness or subclinical myotonic discharges before or during periods of episodic muscle weakness or paralysis. Ingestion of Ca2+ alleviates HyperKPP symptoms, but the mechanism is unknown because lowering extracellular [Ca2+] ([Ca2+]e) has no effect on force development in normal muscles under normal conditions. Lowering [Ca2+]e, however, is known to increase the inactivation of voltage-gated cation channels, especially when the membrane is depolarized. Two hypotheses were tested: (1) lowering [Ca2+]e depresses force in normal muscles under conditions that depolarize the cell membrane; and (2) HyperKPP muscles have a greater sensitivity to low Ca2+-induced force depression because many fibers are depolarized, even at a normal [K+]e. In wild type muscles, lowering [Ca2+]e from 2.4 to 0.3 mM had little effect on tetanic force and membrane excitability at a normal K+ concentration of 4.7 mM, whereas it significantly enhanced K+-induced depression of force and membrane excitability. In HyperKPP muscles, lowering [Ca2+]e enhanced the K+-induced loss of force and membrane excitability not only at elevated [K+]e but also at 4.7 mM K+. Lowering [Ca2+]e increased the incidence of generating fast and transient contractures and gave rise to a slower increase in unstimulated force, especially in HyperKPP muscles. Lowering [Ca2+]e reduced the efficacy of salbutamol, a β2 adrenergic receptor agonist and a treatment for HyperKPP, to increase force at elevated [K+]e. Replacing Ca2+ by an equivalent concentration of Mg2+ neither fully nor consistently reverses the effects of lowering [Ca2+]e. These results suggest that the greater Ca2+ sensitivity of HyperKPP muscles primarily relates to (1) a greater effect of Ca2+ in depolarized fibers and (2) an increased proportion of depolarized HyperKPP muscle fibers compared with control muscle fibers, even at normal [K+]e.
Fe dopants and surface adatoms versus nontrivial topology of single-crystalline Bi2Se3
Authors: Chrobak M , Maćkosz K , Jurczyszyn M , Dobrzański M , Nowak K , Ślęzak T , Zając M , Sikora M , Rams M , Eelbo T , Stępień J , Waśniowska M , Mathon O , Yakhou-Harris F , Merkel D G , Miotkowski I , Kąkol Z , Kozłowski A , Przybylski M , Tarnawski Z
Published: April 2020

Both preserved gapless states and gapping of Dirac states due to broken time reversal symmetry in bismuth chalcogenide topological insulators with surface and bulk magnetic impurities have been observed and reported in the literature. In order to shed more light on the mechanism of such effects we have performed comprehensive element selective study of the impact of Fe impurity position in the Bi2Se3 lattice on its magnetism. The iron atoms were imbedded in the structure (volume dopants) or deposited on the surface (adatoms) and they revealed striking phenomena. Volume doping preserves non-trivial topology of Bi1.98Fe0.02Se3. Fe atoms not only substitute Bi, but also locate in van der Waals gap. The former are magnetically isotropic, while the latter reveal large magnetic moment (4.5 μ
B) with perpendicular anisotropy if located near the surface. Majority of Fe adatoms on the surface of Bi2Se3 exhibit weaker moment (3.5 μ
B) with in-plane anisotropy, as expected for non-interacting species. Negligible interaction between surface electronic states and magnetic adatoms is confirmed by identical vibration spectra of Fe deposited on TI surface of Bi2Se3 and non-TI surface of Bi2S3. The data gathered show how indispensable is the knowledge of the magnetic impurity distribution for applications of bismuth chalcogenide systems.
About the foundation of the Kubo generalized cumulants theory: a revisited and corrected approach
Authors: Bianucci Marco , Bologna Mauro
Published: April 2020

More than fifty years ago, in a couple of seminal works (Kubo 1962 J. Phys. Soc. Japan
17 1100–20; Kubo 1963 J. Math. Phys. 4 174–83) Kubo introduced the important idea of generalized cumulants, extending to stochastic operators this concept implicitly introduced by Laplace in 1810. Kubo’s idea has been applied in several branches of physics, where the result of the average process is a Lioville operator or an effective time evolution operator for the density matrix of spin systems or the reduced density matrix for boson-fermions etc. Despite this success, the theoretical developments in these Kubo works pose problems that were highlighted many years ago by Fox and van Kampen and never solved. These weaknesses and errors, in particular concerning the factorization property of exponentials of cumulants and the explicit expressions that give generalized cumulants in terms of generalized moments and vice-versa, caused some perplexity (and confusion) about the possible application of this procedure, limiting its use, in practice. In the present paper, we give a sound ground to the approach to cumulant operators, working in a general framework that shows the potentiality of the old Kubo idea, today not yet fully exploited. It results that, for the same moment operators, different definitions of generalized cumulants can be adopted. A general Kubo–Meeron closed-form formula giving cumulant operators in terms of moment operators cannot be obtained, but the reverse one, cumulants in terms of operators, is given and, noticeably, formally it does not depend on the specific nature of the moments, but just on the definition of the generalized cumulants.
Quantifying the uncertainty introduced by internal climate variability in projections of Canadian crop production
Authors: Qian Budong , Jing Qi , Smith Ward , Grant Brian , Cannon Alex J , Zhang Xuebin
Published: April 2020

Internal climate variability (ICV) is one of the major sources of uncertainty in climate projections, yet it is seldom quantified for projections of crop production. Our study focuses on quantifying the uncertainty due to ICV in projections of crop productions in Canada. We utilize climate scenarios from two large ensembles (LEs, CanESM2-LE and CanRCM4-LE with 25 members each) as inputs to the crop models in the Decision Support System for Agrotechnology Transfer. We simulate crop yields for canola, maize and spring wheat under the future climates of four global warming levels. The coefficient of variation (CV) of the projected crop production across the LE members is used to quantify the uncertainty related to ICV and this is compared with the CVs generated using the 20 GCMs in the Coupled Model Intercomparison Project Phase 5 (CMIP5). Crop production in Canada could increase with global warming, e.g. spring wheat production could increase by up to 21% at the warming level of 3.0 °C. The projections often produce larger uncertainty associated with the GCMs than from ICV at all warming levels above 2.0 °C. The results from an asymptotic test for the equality of CVs show a significant difference in CVs of projections of canola production between CanESM2-LE/CanRCM4-LE and CMIP5 for the warming level of 3.0 °C. However, the test results do not indicate a significant difference among the ensembles at all four warming levels for maize and spring wheat. The uncertainty due to ICV is often comparable to that associated with GCMs at the warming level of 1.5 °C, e.g. a CV of 6.0 and 6.4% for CanESM2-LE and CanRCM4-LE and 6.6% for CMIP5 in the projections of spring wheat production. We conclude there is a need to account for uncertainty related to ICV in projections of Canadian crop production, especially at lower warming levels.
Stationary state degeneracy of open quantum systems with non-abelian symmetries
Authors: Zhang Zh , Tindall J , Mur-Petit J , Jaksch D , Buča B
Published: April 2020

We study the null space degeneracy of open quantum systems with multiple non-abelian, strong symmetries. By decomposing the Hilbert space representation of these symmetries into an irreducible representation involving the direct sum of multiple, commuting, invariant subspaces we derive a tight lower bound for the stationary state degeneracy. We apply these results within the context of open quantum many-body systems, presenting three illustrative examples: a fully-connected quantum network, the XXX Heisenberg model and the Hubbard model. We find that the derived bound, which scales at least cubically in the system size the SU(2) symmetric cases, is often saturated. Moreover, our work provides a theory for the systematic block-decomposition of a Liouvillian with non-abelian symmetries, reducing the computational difficulty involved in diagonalising these objects and exposing a natural, physical structure to the steady states—which we observe in our examples.
Neural networks and kernel ridge regression for excited states dynamics of CH2NH 2+ : From single-state to multi-state representations and multi-property machine learning models
Authors: Westermayr Julia , Faber Felix A , Christensen Anders S , von Lilienfeld O Anatole , Marquetand Philipp
Published: April 2020

Excited-state dynamics simulations are a powerful tool to investigate photo-induced reactions of molecules and materials and provide complementary information to experiments. Since the applicability of these simulation techniques is limited by the costs of the underlying electronic structure calculations, we develop and assess different machine learning models for this task. The machine learning models are trained onab initiocalculations for excited electronic states, using the methylenimmonium cation (CH2NH2+) as a model system. Two distinct strategies for modeling excited state properties are tested in this work. The first strategy is to treat each state separately in a kernel ridge regression model and all states together in a multiclass neural network. The second strategy is to instead encode the state as input into the model, which is tested with both models. Numerical evidence suggests that using the state as input yields the best performance. An important goal for excited-state machine learning models is their use in dynamics simulations, which needs not only state-specific information but also couplings, i.e. properties involving pairs of states. Accordingly, we investigate how well machine learning models can predict the couplings. Furthermore, we explore how combining all properties in a single neural network affects the accuracy. Finally, machine learning predicted energies, forces, and couplings are used to carry out excited-state dynamics simulations. Results demonstrate the scopes and possibilities of machine learning to model excited-state properties.
Data-Driven Development of an Institutional “Gross-Only” Policy for the Examination of Select Surgical Pathology Specimens
Authors: Arispe Angulo Karen R , Farooq Ayesha , Samra Hasan , Weldemichael Wegahta , Anderson Jennifer , Jorns Julie M
Published: April 2020

Objectives

To determine diagnostic, workflow, and economic implications of instituting a gross-only policy at our institution.

Methods

Retrospective (2017) key word searches were performed to identify “gross-only” cases for which microscopic evaluation could potentially be omitted, but was performed, and those who underwent gross evaluation per surgeon request. Cases were evaluated for type(s), part(s), block volume, turnaround time, demographics, and diagnosis. Laboratory costs and reimbursement were evaluated.

Results

In total, 448 potential gross-only cases with 472 specimens consisted of atherosclerotic plaques (33.5%), bariatric stomach/bowel (32.6%), hernia (15.7%), heart valves (12.7%), and other (5.9%). Four (2.6%) bariatric surgery cases had Helicobacter pylori infection; these were the only cases with “significant” histologic findings. Cost analysis revealed that converting all potential gross-only specimens to gross only would result in overall losses based on average reimbursements, most influenced by bariatric specimens (Current Procedural Terminology code 88307), comprising 65.2% of estimated loss.

Conclusions

Establishing a gross-only policy should be guided by established recommendations but institutionally individualized and data driven. It was reasonable for us to establish a gross-only policy for most evaluated specimens, while excluding bariatric stomach specimens in which microscopic pathology could be missed, given the lack of H pylori screening at our institution.
Phigaro: high-throughput prophage sequence annotation
Authors: Starikova Elizaveta V , Tikhonova Polina O , Prianichnikov Nikita A , Rands Chris M , Zdobnov Evgeny M , Ilina Elena N , Govorun Vadim M
Published: April 2020

Phigaro is a standalone command-line application that is able to detect prophage regions taking raw genome and metagenome assemblies as an input. It also produces dynamic annotated ‘prophage genome maps’ and marks possible transposon insertion spots inside prophages. It is applicable for mining prophage regions from large metagenomic datasets.

Availability and implementation

Source code for Phigaro is freely available for download at https://github.com/bobeobibo/phigaro along with test data. The code is written in Python.

Supplementary information

Supplementary data are available at Bioinformatics online.
Loss of RBBP4 results in defective inner cell mass, severe apoptosis, hyperacetylated histones and preimplantation lethality in mice†
Authors: Miao Xiaosu , Sun Tieqi , Barletta Holly , Mager Jesse , Cui Wei
Published: April 2020

Retinoblastoma-binding protein 4 (RBBP4) (also known as chromatin-remodeling factor RBAP48) is an evolutionarily conserved protein that has been involved in various biological processes. Although a variety of functions have been attributed to RBBP4 in vitro, mammalian RBBP4 has not been studied in vivo. Here we report that RBBP4 is essential during early mouse embryo development. Although Rbbp4 mutant embryos exhibit normal morphology at E3.5 blastocyst stage, they cannot be recovered at E7.5 early post-gastrulation stage, suggesting an implantation failure. Outgrowth (OG) assays reveal that mutant blastocysts cannot hatch from the zona or can hatch but then arrest without further development. We find that while there is no change in proliferation or levels of reactive oxygen species, both apoptosis and histone acetylation are significantly increased in mutant blastocysts. Analysis of lineage specification reveals that while the trophoblast is properly specified, both epiblast and primitive endoderm lineages are compromised with severe reductions in cell number and/or specification. In summary, these findings demonstrate the essential role of RBBP4 during early mammalian embryogenesis.
Spectral and Anatomical Patterns of Large-Scale Synchronization Predict Human Attentional Capacity
Authors: Rouhinen Santeri , Siebenhühner Felix , Palva J Matias , Palva Satu
Published: April 2020

The capacity of visual attention determines how many visual objects may be perceived at any moment. This capacity can be investigated with multiple object tracking (MOT) tasks, which have shown that it varies greatly between individuals. The neuronal mechanisms underlying capacity limits have remained poorly understood. Phase synchronization of cortical oscillations coordinates neuronal communication within the fronto-parietal attention network and between the visual regions during endogenous visual attention. We tested a hypothesis that attentional capacity is predicted by the strength of pretarget synchronization within attention-related cortical regions. We recorded cortical activity with magneto- and electroencephalography (M/EEG) while measuring attentional capacity with MOT tasks and identified large-scale synchronized networks from source-reconstructed M/EEG data. Individual attentional capacity was correlated with load-dependent strengthening of theta (3–8 Hz), alpha (8–10 Hz), and gamma-band (30–120 Hz) synchronization that connected the visual cortex with posterior parietal and prefrontal cortices. Individual memory capacity was also preceded by crossfrequency phase–phase and phase–amplitude coupling of alpha oscillation phase with beta and gamma oscillations. Our results show that good attentional capacity is preceded by efficient dynamic functional coupling and decoupling within brain regions and across frequencies, which may enable efficient communication and routing of information between sensory and attentional systems.
Beneficial Effects of Cannabis on Blood–Brain Barrier Function in Human Immunodeficiency Virus
Authors: Ellis Ronald J , Peterson Scott , Cherner Mariana , Morgan Erin , Schrier Rachel , Tang Bin , Hoenigl Martin , Letendre Scott , Iudicello Jenny
Published: April 2020

Background

Human immunodeficiency virus (HIV) infection leads to blood–brain barrier (BBB) dysfunction that does not resolve despite viral suppression on antiretroviral therapy (ART) and is associated with adverse clinical outcomes. In preclinical models, cannabis restores BBB integrity.

Methods

We studied persons with HIV (PWH) and HIV-negative (HIV−) individuals who had used cannabis recently. We assessed 2 biomarkers of BBB permeability: the cerebrospinal fluid (CSF) to serum albumin ratio (CSAR) and CSF levels of soluble urokinase plasminogen activator receptor (suPAR), a receptor for uPA, a matrix-degrading proteolytic enzyme that disrupts the BBB. A composite index of the BBB markers was created using principal components analysis. Neural injury was assessed using neurofilament light (NFL) in CSF by immunoassay.

Results

Participants were 45 PWH and 30 HIV− individuals of similar age and ethnicity. Among PWH, higher CSF suPAR levels correlated with higher CSAR values (r = 0.47, P < .001). PWH had higher (more abnormal) BBB index values than HIV− individuals (mean ± SD, 0.361 ± 1.20 vs −0.501 ± 1.11; P = .0214). HIV serostatus interacted with cannabis use frequency, such that more frequent use of cannabis was associated with lower BBB index values in PWH but not in HIV− individuals. Worse BBB index values were associated with higher NFL in CSF (r = 0.380, P = .0169).

Conclusions

Cannabis may have a beneficial impact on HIV-associated BBB injury. Since BBB disruption may permit increased entry of toxins such as microbial antigens and inflammatory mediators, with consequent CNS injury, these results support a potential therapeutic role of cannabis among PWH and may have important treatment implications for ART effectiveness and toxicity.
COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options
Authors: Guzik Tomasz J , Mohiddin Saidi A , Dimarco Anthony , Patel Vimal , Savvatis Kostas , Marelli-Berg Federica M , Madhur Meena S , Tomaszewski Maciej , Maffia Pasquale , D’Acquisto Fulvio , Nicklin Stuart A , Marian Ali J , Nosalski Ryszard , Murray Eleanor C , Guzik Bartlomiej , Berry Colin , Touyz Rhian M , Kreutz Reinhold , Wang Dao Wen , Bhella David , Sagliocco Orlando , Crea Filippo , Thomson Emma C , McInnes Iain B
Published: April 2020

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades. We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies. While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system. Risk of severe infection and mortality increase with advancing age and male sex. Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer. The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC). Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) —a homologue of ACE—to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI). While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. Hence, patients should not discontinue their use. Moreover, renin–angiotensin–aldosterone system (RAAS) inhibitors might be beneficial in COVID-19. Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19. Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications. Preventive measures (social distancing and social isolation) also increase cardiovascular risk. Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.
Age-Stage, Two-Sex Life Table of Chrysodeixis chalcites (Lepidoptera: Noctuidae) at Constant Temperatures on Semi-Synthetic Diet
Authors: del Pino Modesto , Cabello Tomás , Hernández-Suárez Estrella
Published: April 2020

The golden twin-spot moth or tomato looper, Chrysodeixis chalcites (Esper), is a polyphagous and worldwide pest that causes important aesthetic damages to banana fruits in the Canary Islands. The life history parameters of C. chalcites were determined under laboratory conditions in base on the age-stage, two-sex life table at 15, 20, 25, 30, and 35°C, 65% relative humidity (RH), and a photoperiod of 16:8 (L:D) h, when it was reared on a semi-synthetic diet. The results show that C. chalcites was able to develop and survive from 15 to 30°C, but no development occurred at 35°C. Developmental threshold temperatures of the egg, larval, pupal, and total preoviposition stages were 10.42, 11.73, 11.22, and 9.42°C, respectively, and their effective accumulated temperatures were 58.31, 265.96, 118.57, and 562.39 degree-days, respectively. The adult longevity was reduced with increasing temperature, which ranged between 16.27 and 34.85 d for females and between 14.27 and 35.21 d for males. The highest values of net reproductive rate (R0) and fecundity were observed at 25°C, with 232.70 offspring and 1,224.74 eggs, respectively. Both the intrinsic rate of increase (r) and finite rate of increase (λ) increased significantly and mean generation time (T) decreased significantly with increasing temperature. These results provide useful information that will allow predicting the impact of climate change on the distribution and population dynamics of C. chalcites and developing successful integrated management programs.
Timing of Communication
Authors: Bhattacharya Puja , Nielsen Kirby , Sengupta Arjun
Published: April 2020

Using an experiment, we demonstrate that a communication regime in which a worker communicates about his intended effort is less effective in: (i) soliciting truthful information; and (ii) motivating effort than one in which he communicates about his past effort. Our experiment uses a real-effort task, which additionally allows us to demonstrate the effects of communication on effort over time. We show that the timing of communication affects the dynamic pattern of work. In both treatments, individuals are most co-operative closest to the time of communication. Our results reveal that the timing of communication is a critical feature that merits attention in the design of mechanisms for information transmission in strategic settings.
Introducing teledermoscopy of possible skin cancers in general practice in Southern Denmark
Authors: Vestergaard Tine , Prasad Sumangali C , Schuster Annette , Laurinaviciene Rasa , Bygum Anette , Munck Anders , Andersen Merethe K
Published: April 2020

Background

The increasing incidence of skin cancers poses a burden to health care systems. General practitioners (GPs) play an important role in triaging these diseases and referring relevant patients to specialists. It is challenging to distinguish benign from malignant skin lesions, and GPs may benefit from diagnostic support from teledermoscopy (TD).

Objectives

To assess whether the introduction of TD in general practice was feasible and might reduce the number of unnecessary referrals to specialists and to assess the diagnostic accuracy and confidence of participating GPs.

Methods

Fifty general practices in Southern Denmark participated. Adult patients presenting to their GP with suspected skin cancer could be included. Images including dermoscopy were taken by the GP and sent for evaluation by specialized dermatologists at a university hospital. Patients were simultaneously referred for a face-to-face evaluation at the university hospital. Diagnoses proposed by the GPs and by TD were compared to the final diagnoses obtained by histopathology or, if not available, face-to-face evaluation.

Results

Five hundred and nineteen patients with 600 suspected skin cancers were included. The final diagnosis was benign in 72.3%. The photo quality was good or fair in 90.5%. GPs reported uncertainty about their diagnoses in 41.5% of cases. The GPs’ positive predictive values for any malignancy and for malignant melanoma were 49.5% and 26.3%, respectively. On evaluation by TD, 31.5% of lesions did not need further in-person assessment.

Conclusion

Useful images of suspicious skin lesions were obtained from general practice, and GPs could benefit from TD to improve their diagnostic accuracy and confidence.
Regional Gray Matter Density Associated With Fast-Paced Walking in Older Adults: A Voxel-Based Morphometry Study
Authors: Chen Nemin , Rosano Caterina , Karim Helmet T , Studenski Stephanie A , Rosso Andrea L
Published: April 2020

Background

Walking speed during fast-paced walking task has been associated with cognitive function. It is unclear what underlying brain structures are related to fast-paced walking. We investigated the association of gray matter (GM) density with fast-paced walking speed and usual-paced walking speed.

Methods

We collected data from 284 older adults from a subset of the Health, Aging, and Body composition study (mean age = 83 [SD = 2.8], 58% women, 41% black). Voxel-wise analyses on magnetic resonance imaging data identified regions of the brain where GM density was associated with fast-paced walking speed. We then extracted GM density for all identified regions and modeled the association with fast-paced walking speed after adjusting for demographic factors, clinical factors, and cognitive function. Analyses were repeated for usual-paced walking. Regions with beta coefficients ≥0.3 m/s were considered to be meaningfully correlated.

Results

GM density of clusters from cortical regions in the right middle and superior frontal gyrus, right postcentral gyrus, and left superior temporal gyrus were positively correlated with fast-paced walking speed in adjusted models. Adjustment for cognitive function had little impact on the findings. Caudate was correlated with usual paced walking speed at coefficient ≥0.3 m/s after adjustment of demographic factors and clinical factors, but not after further adjustment of cognitive function.

Conclusions

Fast-paced walking speed was correlated with GM density of right middle and superior frontal gyrus, right postcentral gyrus, and left superior temporal gyrus, and could potentially provide evidence about subclinical structural change of brain related to aging.
Multidimensional penalized splines for incidence and mortality-trend analyses and validation of national cancer-incidence estimates
Authors: Uhry Zoé , Chatignoux Edouard , Dantony Emmanuelle , Colonna Marc , Roche Laurent , Fauvernier Mathieu , Defossez Gautier , Leguyader-Peyrou Sandra , Monnereau Alain , Grosclaude Pascale , Bossard Nadine , Remontet Laurent
Published: April 2020

Background

Cancer-incidence and mortality-trend analyses require appropriate statistical modelling. In countries without a nationwide cancer registry, an additional issue is estimating national incidence from local-registry data. The objectives of this study were to (i) promote the use of multidimensional penalized splines (MPS) for trend analyses; (ii) estimate the national cancer-incidence trends, using MPS, from only local-registry data; and (iii) propose a validation process of these estimates.

Methods

We used an MPS model of age and year for trend analyses in France over 1990–2015 with a projection up to 2018. Validation was performed for 22 cancer sites and relied essentially on comparison with reference estimates that used the incidence/health-care ratio over the period 2011–2015. Alternative estimates that used the incidence/mortality ratio were also used to validate the trends.

Results

In the validation assessment, the relative differences of the incidence estimates (2011–2015) with the reference estimates were <5% except for testis cancer in men and < 7% except for larynx cancer in women. Trends could be correctly derived since 1990 despite incomplete histories in some registries. The proposed method was applied to estimate the incidence and mortality trends of female lung cancer and prostate cancer in France.

Conclusions

The validation process confirmed the validity of the national French estimates; it may be applied in other countries to help in choosing the most appropriate national estimation method according to country-specific contexts. MPS form a powerful statistical tool for trend analyses; they allow trends to vary smoothly with age and are suitable for modelling simple as well as complex trends thanks to penalization. Detailed trend analyses of lung and prostate cancers illustrated the suitability of MPS and the epidemiological interest of such analyses.
Clinical and Clinical-Pharmacogenetic Models for Prediction of the Most Common Psychiatric Complications Due to Dopaminergic Treatment in Parkinson’s Disease
Authors: Redenšek Sara , Jenko Bizjan Barbara , Trošt Maja , Dolžan Vita
Published: April 2020

Background

The most common psychiatric complications due to dopaminergic treatment in Parkinson’s disease are visual hallucinations and impulse control disorders. Their development depends on clinical and genetic factors.

Methods

We evaluated the simultaneous effect of 16 clinical and 34 genetic variables on the occurrence of visual hallucinations and impulse control disorders. Altogether, 214 Parkinson’s disease patients were enrolled. Their demographic, clinical, and genotype data were obtained. Clinical and clinical-pharmacogenetic models were built by The Least Absolute Shrinkage and Selection Operator penalized logistic regression. The predictive capacity was evaluated with the cross-validated area under the receiver operating characteristic curve (AUC).

Results

The clinical-pharmacogenetic index for prediction of visual hallucinations encompassed age at diagnosis (OR = 0.99), rapid eye movement (REM) sleep behavior disorder (OR = 2.27), depression (OR = 1.0002), IL6 rs1800795 (OR = 0.99), GPX1 s1050450 (OR = 1.07), COMT rs165815 (OR = 0.69), MAOB rs1799836 (OR = 0.97), DRD3 rs6280 (OR = 1.32), and BIRC5 rs8073069 (OR = 0.94). The clinical-pharmacogenetic index for prediction of impulse control disorders encompassed age at diagnosis (OR = 0.95), depression (OR = 1.75), beta-blockers (OR = 0.99), coffee consumption (OR = 0.97), NOS1 rs2682826 (OR = 1.15), SLC6A3 rs393795 (OR = 1.27), SLC22A1 rs628031 (OR = 1.19), DRD2 rs1799732 (OR = 0.88), DRD3 rs6280 (OR = 0.88), and NRG1 rs3924999 (OR = 0.96). The cross-validated AUCs of clinical and clinical-pharmacogenetic models for visual hallucinations were 0.60 and 0.59, respectively. The AUCs of clinical and clinical-pharmacogenetic models for impulse control disorders were 0.72 and 0.71, respectively. The AUCs show that the addition of selected genetic variables to the analysis does not contribute to better prediction of visual hallucinations and impulse control disorders.

Conclusions

Models could be improved by a larger cohort and by addition of other types of Parkinson’s disease biomarkers to the analysis.
The Affective Foundation of Political Opinion Expression on Social Media: A Panel Analysis
Authors: Heiss Raffael
Published: April 2020

Social media (SM) allow citizens to not only read news but also express their political opinions. Drawing from cognitive appraisal and affective intelligence theory, this study investigated the affective foundation of political opinion expression on social media (POESM) using two-wave panel data. The results indicate that enthusiasm and anger stimulated POESM but only for individuals with a minimum threshold motivation to use SM for political purposes. Among the politically motivated, anxiety increased POESM for individuals with low political knowledge but lessened POESM for ones with high political knowledge. Thus, emotional states can be powerful drivers of POESM. In contexts with low levels of POESM, emotions may stimulate online discussion as well as contribute to the further emotionalization of political debates.
In vitro susceptibility to fostemsavir is not affected by long-term exposure to antiviral therapy in MDR HIV-1-infected patients
Authors: Saladini Francesco , Giannini Alessia , Giammarino Federica , Maggiolo Franco , Vichi Francesca , Corbelli Giulio M , Galli Andrea , Bigoloni Alba , Poli Andrea , Santoro Maria M , Zazzi Maurizio , Castagna Antonella
Published: April 2020

Objectives

Fostemsavir is the prodrug of the HIV-1 attachment inhibitor temsavir and is currently under clinical assessment in heavily treatment-experienced patients with limited therapeutic options. We evaluated the genotypic and phenotypic susceptibility to temsavir in a panel of samples collected from patients harbouring MDR strains enrolled in the Italian PRESTIGIO Registry.

Methods

Plasma samples from 24 patients were used for HIV-1 gp120 sequencing, while viral tropism and susceptibility to temsavir were assessed through a homemade phenotypic assay with pseudotyped viruses expressing patient-derived Env protein.

Results

Of the 24 patients enrolled, 18 (75%) were male, median (IQR) age was 55 years (52–61), time since HIV-1 diagnosis was 27 years (24–30), time on ART was 26 years (23–27) and 11 (46%) had a previous AIDS diagnosis. Exposure to entry inhibitors (maraviroc and/or enfuvirtide) had occurred in 19 (79%) patients. Among 23/24 gp120 sequences obtained, temsavir resistance-associated mutations (RAMs) were detected in three cases (two M426L and one S375N). Pseudotyped viruses were obtained from 23/24 samples and viral tropism was CXCR4-tropic, CCR5-tropic and dual/mixed-tropic in six, nine and eight cases, respectively. Phenotypic susceptibility to temsavir was comparable to the reference WT viruses NL4-3 and AD8 in all samples, irrespective of RAMs. Viral tropism and exposure to entry inhibitors did not impact temsavir susceptibility.

Conclusions

These data support the use of fostemsavir as a valuable therapy option in patients harbouring MDR virus. The role of laboratory testing in optimal screening of patients eligible for fostemsavir treatment remains to be investigated.