bluuebunny/crossref_metadata_2025 huggingface dataset:
Cosmic evolution of molecular gas mass density from an empirical relationship between L1.4 GHz and L′CO
Authors: Orellana-González G , Ibar E , Leiton R , Thomson A P , Cheng C , Ivison R J , Herrera-Camus R , Messias H , Calderón-Castillo P , Hughes T M , Leeuw L
Published: May 2020

Historically, GHz radio emission has been used extensively to characterize the star-formation activity in galaxies. In this work, we look for empirical relationships amongst the radio luminosity, the infrared luminosity, and the CO-based molecular gas mass. We assemble a sample of 278 nearby galaxies with measurements of radio continuum and total infrared emission, and the 12CO J = 1–0 emission line. We find a correlation between the radio continuum and the CO emission line (with a scatter of 0.36 dex), in a large sample of different kinds of galaxies. Making use of this correlation, we explore the evolution of the molecular gas mass function and the cosmological molecular gas mass density in six redshift bins up to z = 1.5. These results agree with previous semi-analytic predictions and direct measurements: the cosmic molecular gas density increases up to z = 1.5. In addition, we find a single plane across five orders of magnitude for the explored luminosities, with a scatter of 0.27 dex. These correlations are sufficiently robust to be used for samples where no CO measurements exist.
Evidence for coupling of evolved star atmospheres and spiral arms of the Milky Way
Authors: Gorski Mark D , Barmby Pauline
Published: May 2020

It is imperative to map the strength and distribution of feedback in galaxies to understand how feedback affects galactic ecosystems. H2O masers act as indicators of energy injection into the interstellar medium. Our goal is to measure the strength and distribution of feedback traced by water masers in the Milky Way. We identify optical counterparts to H2O masers discovered by the HOPS survey. The distribution and luminosities of H2O masers in the Milky Way are determined using parallax measurements derived from the second Gaia Data Release. We provide evidence of a correlation between evolved stars, as traced by H2O masers, and the spiral structure of the Milky Way, suggesting a link between evolved stars and the Galactic environment.
8 in 10 Stars in the Milky Way Bulge experience stellar encounters within 1000 AU in a gigayear
Authors: McTier Moiya A S , Kipping David M , Johnston Kathryn
Published: May 2020

The Galactic bulge is a tumultuous dense region of space, packed with stars separated by far smaller distances than those in the Solar neighbourhood. A quantification of the frequency and proximity of close stellar encounters in this environment dictates the exchange of material, disruption of planetary orbits, and threat of sterilizing energetic events. We present estimated encounter rates for stars in the Milky Way bulge found using a combination of numerical and analytical methods. By integrating the orbits of bulge stars with varying orbital energy and angular momentum to find their positions over time, we were able to estimate how many close stellar encounters the stars should experience as a function of orbit shape. We determined that ∼80 per cent of bulge stars have encounters within 1000 AU and that half of bulge stars will have >35 such encounters, both over a gigayear. Our work has interesting implications for the long-term survivability of planets in the Galactic bulge.
The binary evolution of SAX J1808.4−3658: implications of an evolved donor star
Authors: Goodwin A J , Woods T E
Published: May 2020

Observations of the accretion powered millisecond pulsar SAX J1808.4−3658 have revealed an interesting binary evolution, with the orbit of the system expanding at an accelerated rate. We use the recent finding that the accreted fuel in SAX J1808.4−3658 is hydrogen depleted to greatly refine models of the progenitor and prior evolution of the binary system. We constrain the initial mass of the companion star to 1.0–1.2 M⊙, more massive than previous evolutionary studies of this system have assumed. We also infer the system must have undergone strongly non-conservative mass transfer in order to explain the observed orbital period changes. We include mass loss due to the pulsar radiation pressure on the donor star, inducing an evaporative wind which is ejected at the inner Lagrangian point of the binary system. The resulting additional loss of angular momentum resolves the discrepancy between conservative mass transfer models and the observed orbital period derivative of this system. We also include a treatment of donor irradiation due to the accretion luminosity, and find this has a non-negligible effect on the evolution of the system.
Astrometric orbits of spectral binary brown dwarfs – I. Massive T dwarf companions to 2M1059−21 and 2M0805+48
Authors: Sahlmann J , Burgasser A J , Bardalez Gagliuffi D C , Lazorenko P F , Ségransan D , Zapatero Osorio M R , Blake C H , Gelino C R , Martín E L , Bouy H
Published: May 2020

Near-infrared spectroscopic surveys have uncovered a population of short-period, blended-light spectral binaries composed of low-mass stars and brown dwarfs. These systems are amenable to orbit determination and individual mass measurements via astrometric monitoring. Here, we present first results of a multiyear campaign to obtain high-precision absolute astrometry for spectral binaries using the Gemini-South and Gemini-North GMOS imagers. We measure the complete astrometric orbits for two systems: 2M0805+48 and 2M1059−21. Our astrometric orbit of 2M0805+48 is consistent with its 2-yr radial velocity orbit determined previously and we find a mass of $66^{+5}_{-14} M_\mathrm{Jup}$ for its T5.5 companion. For 2M1059−21, we find a 1.9-yr orbital period and a mass of $67^{+4}_{-5} M_\mathrm{Jup}$ for its T3.5 companion. We demonstrate that sub-milliarcsecond absolute astrometry can be obtained with both GMOS imagers and that this is an efficient avenue for confirming and characterizing ultracool binary systems.
IRIS3: integrated cell-type-specific regulon inference server from single-cell RNA-Seq
Authors: Ma Anjun , Wang Cankun , Chang Yuzhou , Brennan Faith H , McDermaid Adam , Liu Bingqiang , Zhang Chi , Popovich Phillip G , Ma Qin
Published: May 2020

A group of genes controlled as a unit, usually by the same repressor or activator gene, is known as a regulon. The ability to identify active regulons within a specific cell type, i.e., cell-type-specific regulons (CTSR), provides an extraordinary opportunity to pinpoint crucial regulators and target genes responsible for complex diseases. However, the identification of CTSRs from single-cell RNA-Seq (scRNA-Seq) data is computationally challenging. We introduce IRIS3, the first-of-its-kind web server for CTSR inference from scRNA-Seq data for human and mouse. IRIS3 is an easy-to-use server empowered by over 20 functionalities to support comprehensive interpretations and graphical visualizations of identified CTSRs. CTSR data can be used to reliably characterize and distinguish the corresponding cell type from others and can be combined with other computational or experimental analyses for biomedical studies. CTSRs can, therefore, aid in the discovery of major regulatory mechanisms and allow reliable constructions of global transcriptional regulation networks encoded in a specific cell type. The broader impact of IRIS3 includes, but is not limited to, investigation of complex diseases hierarchies and heterogeneity, causal gene regulatory network construction, and drug development. IRIS3 is freely accessible from https://bmbl.bmi.osumc.edu/iris3/ with no login requirement.
Novel insights into the disease transcriptome of human diabetic glomeruli and tubulointerstitium
Authors: Levin Anna , Reznichenko Anna , Witasp Anna , Liu Peidi , Greasley Peter J , Sorrentino Antonio , Blondal Thorarinn , Zambrano Sonia , Nordström Johan , Bruchfeld Annette , Barany Peter , Ebefors Kerstin , Erlandsson Fredrik , Patrakka Jaakko , Stenvinkel Peter , Nyström Jenny , Wernerson Annika
Published: May 2020

Background

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease, affecting ∼30% of the rapidly growing diabetic population, and strongly associated with cardiovascular risk. Despite this, the molecular mechanisms of disease remain unknown.

Methods

RNA sequencing (RNAseq) was performed on paired, micro-dissected glomerular and tubulointerstitial tissue from patients diagnosed with DN [n = 19, 15 males, median (range) age: 61 (30–85) years, chronic kidney disease stages 1–4] and living kidney donors [n = 20, 12 males, median (range) age: 56 (30–70) years].

Results

Principal component analysis showed a clear separation between glomeruli and tubulointerstitium transcriptomes. Differential expression analysis identified 1550 and 4530 differentially expressed genes, respectively (adjusted P < 0.01). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses highlighted activation of inflammation and extracellular matrix (ECM) organization pathways in glomeruli, and immune and apoptosis pathways in tubulointerstitium of DN patients. Specific gene modules were associated with renal function in weighted gene co-expression network analysis. Increased messengerRNA (mRNA) expression of renal damage markers lipocalin 2 (LCN) and hepatitis A virus cellular receptor1 (HAVCR1) in the tubulointerstitial fraction was observed alongside higher urinary concentrations of the corresponding proteins neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in DN patients.

Conclusions

Here we present the first RNAseq experiment performed on paired glomerular and tubulointerstitial samples from DN patients. We show that prominent disease-specific changes occur in both compartments, including relevant cellular processes such as reorganization of ECM and inflammation (glomeruli) as well as apoptosis (tubulointerstitium). The results emphasize the potential of utilizing high-throughput transcriptomics to decipher disease pathways and treatment targets in this high-risk patient population.
Multiple Equilibria in Open Economies with Collateral Constraints
Authors: Schmitt-Grohé Stephanie , Uribe Martín
Published: May 2020

This article establishes the existence of multiple equilibria in infinite-horizon open economy models in which the value of tradable and non-tradable endowments serves as collateral. In this environment, the economy displays self-fulfilling financial crises in which pessimistic views about the value of collateral induce agents to deleverage. Under plausible calibrations, there exist equilibria with underborrowing. This result stands in contrast to the overborrowing result stressed in the related literature. Underborrowing emerges in the present context because in economies that are prone to self-fulfilling financial crises, individual agents engage in excessive precautionary savings as a way to self-insure.
South Dakota’s “Trust Task Force”
Authors: Goetzinger Patrick G , Simmons Thomas E
Published: May 2020

The State of South Dakota is known internationally as a premier trust situs jurisdiction. Its top ranking is due to a number of factors. Among those factors is a committed band of gubernatorial appointees—both lawyers and non-lawyers—who consider, debate and draft proposed legislation for the South Dakota Legislature each year. This “Trust Task Force” was created by the Governor of the State more than twenty years ago. This article traces the origin and evolution of the South Dakota Trust Task Force, its achievements and its inner workings. It compares the legislative process to enact trust laws in other leading American jurisdictions while commenting on additional important factors which underpin a top ranking among competitor trust jurisdictions.
7Film Theory
Authors: Bettinson Gary
Published: May 2020

Six exemplary works of film theory, published in 2018–19, receive consideration in this chapter: Johannes Riis and Aaron Taylor’s anthology Screening Characters: Theories of Character in Film, Television, and Interactive Media; Murray Pomerance’s Virtuoso: Film Performance and the Actor’s Magic; Jonathan Kirshner and Jon Lewis’s edited collection When the Movies Mattered: The New Hollywood Revisited; Jeff Menne’s Post-Fordist Cinema: Hollywood Auteurs and the Corporate Counterculture; Wieland Schwanebeck and Douglas McFarland’s edited volume Patricia Highsmith on Screen; and Clara Bradbury-Rance’s Lesbian Cinema after Queer Theory. The chapter is organized into three sections: 1. Character Engagement and Performance; 2. Revisiting the New Hollywood; 3. A Highsmith Hinge.
An integrative approach distinguishes three new species of Abyssochrysoidea (Mollusca: Caenogastropoda) associated with organic falls of the deep south-west Atlantic
Authors: Souza Bruno H M , Passos Flávio D , Shimabukuro Maurício , Sumida Paulo Y G
Published: May 2020

Two new species of Rubyspira and one of Cordesia (Gastropoda: Abyssochrysoidea) are described morphologically and genetically, based on specimens collected from whale bones and wood parcels artificially implanted in the deep south-west Atlantic Ocean, at c. 1500 and 3300 m depths. Rubyspira pescaprae sp. nov. and R. elongata sp. nov. occur preferentially on whale bones. Cordesia atlantica sp. nov. is dominant on wood parcels. Distribution of Cordesia was hitherto only associated with hydrocarbon seeps off West Africa. Stable isotopes and gut content analyses were carried out to check possible trophic pathways. Both Rubyspira species are bone eaters, while Cordesia atlantica seems to rely on a wider range of food sources, including juveniles of wood-specialized xylophagid bivalves. Morphological and genetic evidence suggest that Rubyspira and Cordesia are more closely related to Abyssochrysos than to any other Abyssochrysoidea snails. In the present study, Cordesia is considered part of the family Abyssochrysidae based on molecular and morphological evidence, such as the presence of a penis and pallial tentacles arrangement.
Effect of Water Stress on Reproduction and Colonization of Podosphaera aphanis of Strawberry
Authors: Rossi Franca G. , Asalf Belachew , Grieu Chloe , Onofre Rodrigo B. , Peres Natalia A. , Gadoury David M. , Stensvand Arne
Published: May 2020

In a number of pathosystems involving the powdery mildews (Erysiphales), plant stress is associated with decreased disease susceptibility and is detrimental to pathogen growth and reproduction. However, in strawberry, anecdotal observations associate severe powdery mildew (Podosphaera aphanis) with water stress. In a 2017 survey of 42 strawberry growers in Norway and California, 40 growers agreed with a statement that water-stressed strawberry plants were more susceptible to powdery mildew compared with nonstressed plants. In repeated in vitro and in vivo experiments, we found that water stress was consistently and significantly unfavorable to conidial germination, infection, and increases in disease severity. Deleterious effects on the pathogen were observed from both preinoculation and postinoculation water stress in the host. Soil moisture content in the range from 0 to 50% was correlated (R2 = 0.897) with germinability of conidia harvested from extant colonies that developed on plants growing at different levels of water stress. These studies confirm that P. aphanis fits the norm for biotrophic powdery mildews and hosts under stress. Mild water stress, compared with a state of optimal hydration, is likely to decrease rather than increase susceptibility of strawberry to P. aphanis. We believe it is possible that foliar symptoms of leaf curling due to diffuse and inconspicuous infection of the lower leaf surfaces by P. aphanis could easily be mistakenly attributed to water stress, which we observed as having a nearly identical leaf curling symptom in strawberry.
“Was It Worth It?”
Authors: Rost Lee , Chen Yiyi , Fain Robert S. , Hartvigson Pehr E. , Park Byung , Thomas Charles R. , Rana Shushan
Published: May 2020

Objectives:

Radiation therapy is a core oncologic treatment, but literature detailing patient satisfaction post-treatment is sparse. The authors conducted a pilot study to determine whether a simple survey would be feasible to administer and could elucidate factors predictive of satisfaction with radiotherapy.

Materials and Methods:

Patients with cancer receiving radiotherapy in an academic radiation oncology department from 2014 to 2015 received a 4-item radiotherapy-focused version of the “Was It Worth It?” questionnaire (r-WIWI) on the last day of treatment and at the first follow-up. Univariate analysis and logistic regression modeling were performed on collected patient and treatment characteristics to explore predictors of satisfaction.

Results:

Two hundred patients completed an r-WIWI questionnaire at treatment completion and 60 at the time of the first follow-up. Seventy-one percent and 90% of patients found radiotherapy worthwhile on the last day of treatment and at first follow-up, respectively. Patients treated during the morning and for a longer duration as measured in elapsed days were more likely to report treatment being worthwhile. Age, sex, race, marital status, employment status, treatment intent or modalities, daily radiation treatment delays, distance traveled, insurance type, site of treatment, and cancer stage were not predictive of patient satisfaction.

Conclusions:

The r-WIWI survey was feasible to administer and most patients reported treatment being worthwhile on the last day of treatment and at first follow-up. Morning treatment times and longer treatment duration as measured in elapsed days were predictive of higher satisfaction in this pilot study. A broader study of factors associated with patient satisfaction with radiotherapy using the r-WIWI is indicated.
Glaucomatous Progression After Lens Extraction in Primary Angle Closure Disease Spectrum
Authors: Song Min Kyung , Sung Kyung Rim , Shin Joong Won , Jo Youn Hye , Won Hun Jae
Published: May 2020

Precis:

Substantial proportion of primary angle closure glaucoma (PACG) eyes showed glaucomatous worsening after successful lens extraction and intraocular pressure (IOP) control, which may suggest that an earlier intervention may be required to prevent PACG.

Purpose:

The purpose of this study was to investigate the longitudinal clinical course of the primary angle closure (PAC) disease spectrum, including PAC, primary angle closure suspect (PACS), and PACG patients, who underwent lens extraction.

Methods:

This retrospective observational study included 77 eyes from patients with PACS, PAC, and PACG who underwent lens extraction and were followed up for >2 years after surgery. The mean, peak, and fluctuation of IOP were analyzed before and after lens extraction among groups. Visual field (VF) mean deviation was compared immediately after lens extraction and the final follow-up. Postoperative glaucoma progression determined by 3 criteria (optic disc/retinal nerve fiber layer photographs, optical coherent tomography, and VF) was compared among the 3 groups.

Results:

Seventeen PACS, 24 PAC, and 36 PACG eyes were included. The mean and peak IOP, and IOP fluctuation IOP were significantly reduced postoperatively in all groups. Postoperative VF mean deviation was significantly aggravated only in the PACG group (from −7.26 to −8.82 dB, P<0.001). The prevalence of postoperative glaucoma progression by at least 1 criterion was significantly higher in PACG, and none of the eyes with PACS and PAC showed VF conversion (PACS, PAC, PACG; 11.8%, 12.5% vs. 61.1% in disc/retinal nerve fiber layer, 11.8%, 8.3% vs. 63.9% in optical coherent tomography, 0%, 0% vs. 33.3% in VF, all P<0.001).

Conclusions:

In the PAC spectrum, lens extraction achieved significant IOP reduction. However, despite IOP control, a substantial proportion of PACG eyes showed glaucomatous progression. This result may suggest that lens extraction should be performed early to prevent PACG.
Middle Ear and Temporal Bone Nonkeratinizing Squamous Cell Carcinomas With DEK-AFF2 Fusion
Authors: Todorovic Emilija , Truong Tra , Eskander Antoine , Lin Vincent , Swanson David , Dickson Brendan C. , Weinreb Ilan
Published: May 2020

Primary squamous cell carcinomas (SCCs) of the middle ear and temporal bone are rare and usually keratinizing by morphology. Nonkeratinizing, basaloid SCCs arising in this area are exceedingly rare, and, due to the anatomic proximity to the skull base, nasopharynx, and nasal sinuses, the differential diagnosis is broad. Most tumors with squamous differentiation arising in these subsites are either viral-induced (human papillomavirus/Epstein-Barr virus) or rarely may have specific molecular alterations (BRD4-NUT,EWSR1-FLItranslocations). Occasional tumors are negative for these findings, and their pathogenesis is unknown. A recently discoveredDEK-AFF2fusion was clinically detected in a series of 2 cases known to the authors. This fusion has been previously reported in the literature in a patient with a base of skull tumor who was an exceptional responder to programmed cell death protein 1 inhibitor therapy. We examine here the histomorphologic and molecular findings of 2 additional cases of an emerging entity. Two male patients were identified. Each had a primary middle ear/temporal bone mass with locally advanced disease. The histology was reviewed, and immunohistochemistry was performed. RNA-based next-generation sequencing was performed for clinical detection of diagnostic or actionable fusions. Both patients had basaloid/nonkeratinizing tumors on biopsy. They were positive for markers of squamous differentiation (HMWK, CK5, and p40). By RNA sequencing, they demonstrated the presence of aDEK-AFF2fusion and were negative forEWSR1andNUTtranslocations. TheDEK-AFF2fusion may define a novel diagnostic category of middle ear and temporal bone nonkeratinizing/basaloid SCCs. This fusion also may represent a potential avenue for immunotherapy in these patients. Further studies are needed to fully explore whether this fusion defines a location-specific clinicopathologic entity.
Cohort Profile: A national prospective cohort study of SARS-CoV-2 pandemic outcomes in the U.S. - The CHASING COVID Cohort Study
Authors: Robertson McKaylee M. , Kulkarni Sarah Gorrell , Berry Amanda , Mirzayi Chloe , Rane Madhura , Chang Mindy , Kochhar Shivani , You William , Maroko Andrew , Zimba Rebecca , Westmoreland Drew , Grov Christian , Parcesepe Angela , Waldron Levi , Nash Denis ,   for the CHASING COVID Cohort Study
Published: May 2020

Purpose

The CHASING COVID Cohort study is a U.S.-based prospective cohort study launched during the upswing of the U.S. COVID-19 epidemic. The objectives are to: 1) estimate and evaluate determinants of the cumulative incidence of SARS-CoV-2 infection, disease, and deaths; 2) assess the impact of the pandemic on psychosocial and economic outcomes; and 3) assess the uptake of pandemic mitigation strategies.

Participants

We began enrolling participants March 28, 2020 using internet-based strategies. Adults ≥18 years residing anywhere in the U.S. or U.S. territories were eligible. 6,753 people are enrolled in the cohort, including participants from all 50 U.S. states, the District of Columbia, Puerto Rico, and Guam. Participants are contacted regularly to complete study assessments, including interviews and specimen collection.

Findings to date

Of 4,247 participants who provided a specimen for baseline serologic testing, 135 were seropositive by screening antibody testing (3.2%, 95% CI 2.7%-3.5%) and 90 were seropositive by confirmatory antibody testing (2.1%, 95% CI 1.7%-2.6%). Cohort data have been used to assess the role of household crowding and the presence of children in the household as potential risk factors for severe COVID-19 early in the U.S. pandemic; to describe the prevalence of anxiety symptoms and its relationship to COVID-19 outcomes and other potential stressors; and to identify preferences for SARS-CoV-2 diagnostic testing when community transmission is on the rise via a discrete choice experiment.

Future plans

The CHASING COVID Cohort Study has outlined a research agenda that involves ongoing monitoring of the cumulative incidence and determinants of SARS-CoV-2 outcomes, mental health outcomes and economic outcomes. Additional priorities include COVID-19 vaccine hesitancy, uptake and effectiveness; incidence, prevalence and correlates of long-haul COVID-19; and the extent and duration of the protective effect of SARS-CoV-2 antibodies.
COVID-19 Pandemic Response Simulation: Impact of Non-pharmaceutical Interventions on Ending Lockdowns
Authors: Lee Serin , Zabinsky Zelda B. , Kofsky Stephen , Liu Shan
Published: May 2020

As many federal and state governments are starting to ease restrictions on non-pharmaceutical interventions (NPIs) used to flatten the curve, we developed an agent-based simulation to model the incidence of COVID-19 in King County, WA under several scenarios. While NPIs were effective in flattening the curve, any relaxation of social distancing strategies yielded a second wave. Even if daily confirmed cases dropped to one digit, daily incidence can peak again to 874 cases without import cases. Therefore, policy makers should be very cautious in reopening society.
Development and validation of direct RT-LAMP for SARS-CoV-2
Authors: Mohon Abu Naser , Hundt Jana , van Marle Guido , Pabbaraju Kanti , Berenger Byron , Griener Thomas , Lisboa Luiz , Church Deirdre , Czub Markus , Greninger Alexander , Jerome Keith , Doolan Cody , Pillai Dylan R.
Published: May 2020

We have developed a reverse-transcriptase loop mediated amplification (RT-LAMP) method targeting genes encoding the Spike (S) protein and RNA-dependent RNA polymerase (RdRP) of SARS-CoV-2. The LAMP assay achieves comparable limit of detection as commonly used RT-PCR protocols based on artificial targets, recombinant Sindbis virus, and clinical samples. Clinical validation of single-target (S gene) LAMP (N=120) showed a positive percent agreement (PPA) of 41/42 (97.62%) and negative percent agreement (NPA) of 77/78 (98.72%) compared to reference RT-PCR. Dual-target RT-LAMP (S and RdRP gene) achieved a PPA of 44/48 (91.97%) and NPA 72/72 (100%) when including discrepant samples. The assay can be performed without a formal extraction procedure, with lyophilized reagents which do need cold chain, and is amenable to point-of-care application with visual detection.
Negative impact of hyperglycemia on Tocilizumab therapy in COVID-19 patients
Authors: Marfella Raffaele , Paolisso Pasquale , Sardu Celestino , Bergamaschi Luca , D’Angelo Emanuela Concetta , Barbieri Michelangela , Rizzo Maria Rosaria , Messina Vincenzo , Maggi Paolo , Coppola Nicola , Pizzi Carmine , Biffi Mauro , Viale Pierluigi , Galié Nazzareno , Paolisso Giuseppe
Published: May 2020

Tocilizumab is used for treating moderate-severe Covid-19 pneumonia by targeting IL-6 receptors (IL-6R) and reducing cytokine release, but the pooled rate ratio among diabetic patients with adverse vs those with the more favorable course was 2.26. To date, the hyperglycemia has been shown to increase IL-6 and IL-6R, which has been suggested as a severity predictor in lung diseases of Covid-19 patients. However, there are no data about the effects of tocilizumab therapy on outcomes of hyperglycemic Covid-19 patients with pneumonia. To investigate this unsolved need, 475 Covid-19 positive patients were retrospectively studied since March 1st, 2020. Among them, 78 patients with pneumonia disease and treated with tocilizumab were further evaluated for a severe outcome (encompassing both the use of mechanical ventilation and/or death). Thirty-one (39.7%) hyperglycemic and 47 (60.3%) normoglycemic Covid-19 positive patients (blood glucose levels >140 mg/dl, at admission and/or during hospital stay) were evaluated. Noteworthy, 20 (64%) of hyperglycemic and 11 (23.4%) of normoglycemic patients were also diabetics (P<0.01). At admission, more elevated IL-6 levels in hyperglycemic patients were found and persists even after Tocilizumab administration. In a risk adjusted Cox-regression analysis, Tocilizumab in hyperglycemic did not attenuate the risks of severe outcome as did in normoglycemic patients (p<0.009). Therefore, we could conclude that reduced effects of Tocilizumab in hyperglycemic patients may due to the higher plasma IL-6 levels. Interestingly, when we added IL-6 levels in a Cox regression model the significance for the tocilizumab effect was lost (p<0.07). In this context, our observations evidence that optimal Covid-19 infection management with tocilizumab is not achieved during hyperglycemia both in diabetic and non-diabetic patients.
Dropout in Neural Networks Simulates the Paradoxical Effects of Deep Brain Stimulation on Memory
Authors: Tan Shawn Zheng Kai , Du Richard , Perucho Jose Angelo Udal , Chopra Shauhrat S. , Vardhanabhuti Varut , Lim Lee Wei
Published: May 2020

Neuromodulation techniques such as Deep Brain Stimulation (DBS) are a promising treatment for memory-related disorders including anxiety, addiction, and dementia. However, the outcome of these treatments appears to be paradoxical, as the use of these techniques can both disrupt and enhance memory even when applied to the same brain target. In this paper, we hypothesize that disruption and enhancement of memory through neuromodulation can be explained by the dropout of engram nodes. We used a convolutional neural network to classify handwritten digits and letters, applying dropout at different stages to simulate DBS effects on engrams. We showed that dropout applied during training improves the accuracy of prediction, whereas dropout applied during testing dramatically decreases accuracy of prediction, which mimics enhancement and disruption of memory, respectively. We further showed that transfer learning of neural networks with dropout had increased accuracy and rate of learning. Dropout during training provided a more robust “skeleton” network where transfer learning can be applied, mimicking the effects of chronic DBS on memory. Overall, we show that dropout of nodes can be a potential mechanism by which neuromodulation techniques such as DBS can both disrupt and enhance memory and provides a unique perspective on this paradox.
The electrophysiological underpinnings of variation in verbal working memory capacity
Authors: Pavlov Yuri G. , Kotchoubey Boris
Published: May 2020

Working memory (WM) consists of short-term storage and executive components. We studied cortical oscillatory correlates of these two components in a large sample of 156 participants to assess separately the contribution of them to individual differences in WM. The participants were presented with WM tasks of above-average complexity. Some of the tasks required only storage in WM, others required storage and mental manipulations. Our data indicate a close relationship between frontal midline theta, central beta activity and the executive components of WM. The oscillatory counterparts of the executive components were associated with individual differences in verbal WM performance. In contrast, alpha activity was not related to the individual differences. The results demonstrate that executive components of WM, rather than short-term storage capacity, play the decisive role in individual WM capacity limits.
Correcting for experiment-specific variability in expression compendia can remove underlying signals
Authors: Lee Alexandra J. , Park YoSon , Doing Georgia , Hogan Deborah A. , Greene Casey S.
Published: May 2020

Motivation

In the last two decades, scientists working in different labs have assayed gene expression from millions of samples. These experiments can be combined into compendia and analyzed collectively to extract novel biological patterns. Technical variability, sometimes referred to as batch effects, may result from combining samples collected and processed at different times and in different settings. Such variability may distort our ability to interpret and extract true underlying biological patterns. As more multi-experiment, integrative analysis methods are developed and available data collections increase in size, it is crucial to determine how technical variability affect our ability to detect desired patterns when many experiments are combined

Objective

We sought to determine the extent to which an underlying signal was masked by technical variability by simulating compendia comprised of data aggregated across multiple experiments.

Method

We developed a generative multi-layer neural network to simulate compendia of gene expression experiments from large-scale microbial and human datasets. We compared simulated compendia before and after introducing varying numbers of sources of undesired variability.

Results

We found that the signal from a baseline compendium was obscured when the number of added sources of variability was small. Perhaps as expected, applying statistical correction methods rescued the underlying signal in these cases. As the number of sources of variability increased, surprisingly, we observed that detecting the original signal became increasingly easier even without correction. In fact, applying statistical correction methods reduced our power to detect the underlying signal.

Conclusion

When combining a modest number of experiments, it is best to correct for experiment-specific noise. However, when many experiments are combined, statistical correction reduces one’s ability to extract underlying patterns.
Diverse GABAergic neurons organize into subtype-specific sublaminae in the ventral lateral geniculate nucleus
Authors: Sabbagh Ubadah , Govindaiah Gubbi , Somaiya Rachana D. , Ha Ryan V. , Wei Jessica C. , Guido William , Fox Michael A.
Published: May 2020

In the visual system, retinal axons convey visual information from the outside world to dozens of distinct retinorecipient brain regions and organize that information at several levels, including either at the level of retinal afferents, cytoarchitecture of intrinsic retinorecipient neurons, or a combination of the two. Two major retinorecipient nuclei which are densely innervated by retinal axons are the dorsal lateral geniculate nucleus (dLGN), which is important for classical image-forming vision, and ventral LGN (vLGN), which is associated with non-image-forming vision. The neurochemistry, cytoarchitecture, and retinothalamic connectivity in vLGN remain unresolved, raising fundamental questions of how it receives and processes visual information. To shed light on these important questions, we labeled neurons in vLGN with canonical and novel cell type-specific markers and studied their spatial distribution and morphoelectric properties. Not only did we find a high percentage of cells in vLGN to be GABAergic, we discovered transcriptomically distinct GABAergic cell types reside in the two major laminae of vLGN, the retinorecipient, external vLGN (vLGNe) and the non-retinorecipient, internal vLGN (vLGNi). Within vLGNe, we identified transcriptionally distinct subtypes of GABAergic cells that are distributed into four adjacent sublaminae. Using trans-synaptic viral tracing andin vitroelectrophysiology, we found cells in each these vLGNe sublaminae receive monosynaptic inputs from the retina. These results not only identify novel subtypes of GABAergic cells in vLGN, they suggest the subtype-specific laminar distribution of retinorecipient cells in vLGNe may be important for receiving, processing, and transmitting light-derived signals in parallel channels of the subcortical visual system.

Graphical abstract.

The vLGN is organized into subtype-specific sublaminae which receive visual input

The ventral lateral geniculate nucleus (vLGN) is part of the visual thalamus. It can broadly be separated into two structural domains or laminae, the external vLGNe (which receives retinal input) and the internal vLGNi (receives no retinal input). In this study, we describe subtypes of transcriptomically distinct GABAergic neurons that populate the vLGN and organize into discrete, adjacent sublaminae in the vLGNe. Taken together, our results show four subtype-specific sublaminae of retinorecipient neurons in vLGNe.
Criticality as a measure of developing proteinopathy in engineered human neural networks
Authors: Valderhaug Vibeke Devold , Heiney Kristine , Ramstad Ola Huse , Braathen Geir , Kuan Wei-Li , Nichele Stefano , Sandvig Axel , Sandvig Ioanna
Published: May 2020

A patterned spread of proteinopathy represents a common characteristic of many neurodegenerative diseases. In Parkinson's disease (PD), misfolded forms of alpha-synuclein proteins aggregate and accumulate in hallmark pathological inclusions termed Lewy bodies and Lewy neurites, which seems to affect selectively vulnerable neuronal populations and propagate within interconnected neuronal networks. Research findings suggest that these proteinopathic inclusions are present at very early timepoints in disease development, even before strong behavioural symptoms of dysfunction arise, but that these underlying pathologies might be masked by homeostatic processes working to maintain the function of the degenerating neural circuits. This study investigates whether inducing the PD-related alpha-synuclein pathology in engineered human neural networks can be associated with changes in network function, and particularly with network criticality states. Self-organised criticality represents the critical point between resilience against perturbation and adaptational flexibility, which appears to be a functional trait in self-organising neural networks, both in vitro and in vivo. By monitoring the developing neural network activity through the use of multielectrode arrays (MEAs) for a period of three weeks following proteinopathy induction, we show that although this developing pathology is not clearly manifest in standard measurements of network function, it may be discerned by differences in network criticality states.
FalseColor-Python: a rapid intensity-leveling and digital-staining package for fluorescence-based slide-free digital pathology
Authors: Serafin Robert , Xie Weisi , Glaser Adam K. , Liu Jonathan T. C
Published: May 2020

Slide-free digital pathology techniques, including nondestructive 3D microscopy, are gaining interest as alternatives to traditional slide-based histology. In order to facilitate clinical adoption of these fluorescence-based techniques, software methods have been developed to convert grayscale fluorescence images into color images that mimic the appearance of standard absorptive chromogens such as hematoxylin and eosin (H&E). However, these false-coloring algorithms often require manual and iterative adjustment of parameters, with results that can be inconsistent in the presence of intensity nonuniformities within an image and/or between specimens (intra- and inter-specimen variability). Here, we present an open-source (Python-based) rapid intensity-leveling and digital-staining package that is specifically designed to render two-channel fluorescence images (i.e. a fluorescent analog of H&E) to the traditional H&E color space for 2D and 3D microscopy datasets. However, this method can be easily tailored for other false-coloring needs. Our package offers (1) automated and uniform false coloring in spite of uneven staining within a large thick specimen, (2) consistent color-space representations that are robust to variations in staining and imaging conditions between different specimens, and (3) GPU-accelerated data processing to allow these methods to scale to large datasets. We demonstrate this platform by generating H&E-like images from cleared tissues that are fluorescently imaged in 3D with open-top light-sheet (OTLS) microscopy, and quantitatively characterizing the results in comparison to traditional slide-based H&E histology.
The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation
Authors: Carley Emma , Stewart Rachel K. , Zieman Abigail , Jalilian Iman , King Diane. E. , Zubek Amanda , Lin Samantha , Horsley Valerie , King Megan C.
Published: May 2020

While the mechanisms by which chemical signals control cell fate have been well studied, how mechanical inputs impact cell fate decisions are not well understood. Here, using the well-defined system of keratinocyte differentiation in the skin, we examine whether and how direct force transmission to the nucleus regulates epidermal cell fate. Using a molecular biosensor, we find that tension on the nucleus through Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes requires integrin engagement in undifferentiated epidermal stem cells, and is released during differentiation concomitant with decreased tension on A-type lamins. LINC complex ablation in mice reveals that LINC complexes are required to repress epidermal differentiationin vivoandin vitroand influence accessibility of epidermal differentiation genes, suggesting that force transduction from engaged integrins to the nucleus plays a role in maintaining keratinocyte progenitors. This work reveals a direct mechanotransduction pathway capable of relaying adhesion-specific signals to regulate cell fate.
The nucleosome DNA entry-exit site is important for transcription termination inSaccharomyces cerevisiae
Authors: Hildreth A. Elizabeth , Ellison Mitchell A. , Francette Alex M. , Seraly Julia M. , Lotka Lauren M. , Arndt Karen M.
Published: May 2020

Compared to other stages in the RNA polymerase II transcription cycle, the role of chromatin in transcription termination is poorly understood. Through a genetic screen, we identified histone mutant strains that exhibit transcriptional readthrough of terminatorsin vivo. Amino acid subtitutions map to the nucleosome DNA entry-exit site. On a genome-wide scale, the strongest H3 mutants revealed increased sense-strand transcription upstream and downstream of Pol II transcribed genes, increased antisense transcription overlapping gene bodies, and reduced nucleosome occupancy particularly at the 3’ ends of genes. Replacement of the native sequence downstream of a gene with a sequence that increases nucleosome occupancyin vivoreduced readthrough transcription and suppressed the effect of a DNA entry-exit site substitution. Our results suggest that nucleosomes can facilitate termination by serving as a barrier to RNA polymerase II progression and highlight the importance of the DNA entry-exit site in maintaining the integrity of the transcriptome.
Impact of referencing scheme on decoding performance of LFP-based brain-machine interface
Authors: Ahmadi Nur , Constandinou Timothy G. , Bouganis Christos-Savvas
Published: May 2020

Objective

There has recently been an increasing interest in local field potential (LFP) for brain-machine interface (BMI) applications due to its desirable properties (signal stability and low bandwidth). LFP is typically recorded with respect to a single unipolar reference which is susceptible to common noise. Several referencing schemes have been proposed to eliminate the common noise, such as bipolar reference, current source density (CSD), and common average reference (CAR). However, to date, there have not been any studies to investigate the impact of these referencing schemes on decoding performance of LFP-based BMIs.

Approach

To address this issue, we comprehensively examined the impact of different referencing schemes and LFP features on the performance of hand kinematic decoding using a deep learning method. We used LFPs chronically recorded from the motor cortex area of a monkey while performing reaching tasks.

Main results

Experimental results revealed that local motor potential (LMP) emerged as the most informative feature regardless of the referencing schemes. Using LMP as the feature, CAR was found to yield consistently better decoding performance than other referencing schemes over long-term recording sessions.

Significance

Overall, our results suggest the potential use of LMP coupled with CAR for enhancing the decoding performance of LFP-based BMIs.
Through-grid wicking enables high-speed cryoEM specimen preparation
Authors: Tan Yong Zi , Rubinstein John L.
Published: May 2020

Blotting times for conventional cryoEM specimen preparation complicate time-resolved studies and lead to some specimens adopting preferred orientations or denaturing at the air-water interface. We show that solution sprayed onto one side of a holey cryoEM grid can be wicked through the grid by a glass fiber filter held against the opposite side, often called the ‘back’ of the grid, producing a film suitable for vitrification. This process can be completed in tens of milliseconds. We combined ultrasonic specimen application and through-grid wicking in a high-speed specimen preparation device that we name ‘Back-it-up’, or BIU. The high liquid-absorption capacity of the glass fiber compared to self-wicking grids appears to make the method relatively insensitive to the amount of sample applied. Consequently, through-grid wicking produces large areas of ice suitable for cryoEM for both soluble and detergent-solubilized protein complexes. The device’s speed increases the number of views for a specimen that suffers from preferred orientations.
Spatiotemporal contribution of neuromesodermal progenitor-derived neural cells in the elongation of developing mouse spinal cord
Authors: Shaker Mohammed R , Lee Ju-Hyun , Kim Kyung Hyun , Kim Veronica Jihyun , Kim Joo Yeon , Lee Ji Yeoun , Sun Woong
Published: May 2020

During vertebrate development, the posterior end of the embryo progressively elongates in a head-to-tail direction to form the body plan. Recent lineage tracing experiments revealed that bi-potent progenitors, called neuromesodermal progenitors (NMPs), produce caudal neural and mesodermal tissues during axial elongation. However, their precise location and contribution to spinal cord development remain elusive. Here we used NMP-specific markers (Sox2 and BraT) and a genetic lineage tracing system to localize NMP progenyin vivo. NMPs were initially located at the tail tip, but were later found in the caudal neural tube, which is a unique feature of mouse development. In the neural tube, they produced neural stem cells (NSCs) and contributed to the spinal cord gradually along the AP axis during axial elongation. Interestingly, NMP-derived NSCs preferentially contributed to the ventral side first and later to the dorsal side at the lumbar spinal cord level, which may be associated with atypical junctional neurulation in mice. Our current observations detail the contribution of NMP progeny to spinal cord elongation and provide insights into how different species uniquely execute caudal morphogenesis.
Monetary and fiscal policy effects in South African economy
Authors: Nuru Naser Yenus
Published: May 2020

Purpose

The main purpose of this study is to see the macroeconomic effects of monetary and fiscal policy shocks in South Africa.

Design/methodology/approach

The joint effects of monetary and fiscal policy are analyzed by applying short-run contemporaneous restrictions for the identification of shocks in an SVAR in order to derive impulse response functions. Hence, a general AB model of (Amisano and Giannini, 1997) identification scheme, which is not recursive, is employed in this study.

Findings

The author shows that monetary tightening leads to a fall in real economic activity and depreciates the exchange rate. And in regard to the fiscal policy, the author calculates an initial government spending multiplier of 0.20, which later peaks at 0.40. The tax multiplier is almost 0 on impact and statistically insignificant. However, the author finds evidence supporting the existence of accommodative stance between monetary policy and fiscal policy, which is important for economic and political decision-making.

Originality/value

Empirical studies that deal with the joint effects of monetary and fiscal policy for South Africa through the SVAR framework are quite limited. This paper, therefore, contributes to the empirical literature on the effects of monetary and fiscal policy in a small open economy like South Africa.