bluuebunny/crossref_metadata_2025 huggingface dataset:
The long and the short of it: unlocking nanopore long-read RNA sequencing data with short-read tools
Authors: Dong Xueyi , Tian Luyi , Gouil Quentin , Kariyawasam Hasaru , Su Shian , De Paoli-Iseppi Ricardo , Joseph Prawer Yair David , Clark Michael B. , Breslin Kelsey , Iminitoff Megan , Blewitt Marnie E. , Law Charity W. , Ritchie Matthew E.
Published: June 2020

Application of Oxford Nanopore Technologies’ long-read sequencing platform to transcriptomic analysis is increasing in popularity. However, such analysis can be challenging due to small library sizes and high sequence error, which decreases quantification accuracy and reduces power for statistical testing. Here, we report the analysis of two nanopore sequencing RNA-seq datasets with the goal of obtaining gene-level and isoform-level differential expression information. A dataset of synthetic, spliced, spike-in RNAs (“sequins”) as well as a mouse neural stem cell dataset from samples with a null mutation of the epigenetic regulatorSmchd1were analysed using a mix of long-read specific tools for preprocessing together with established short-read RNA-seq methods. We usedlimma-voomto perform differential gene expression analysis, and the novelFLAMESpipeline to perform isoform identification and quantification, followed byDRIMSeqandlimma-diffSplice(withstageR) to perform differential transcript usage analysis. We compared results from the sequins dataset to the ground truth, and results of the mouse dataset to a previous short-read study on equivalent samples. Overall, our work shows that transcriptomic analysis of long-read nanopore data using short-read software and methods that are already in wide use can yield meaningful results.
SARS-CoV-2 infection of primary human lung epithelium for COVID-19 modeling and drug discovery
Authors: Mulay A. , Konda B. , Garcia G. , Yao C. , Beil S. , Sen C. , Purkayastha A. , Kolls J. K. , Pociask D. A. , Pessina P. , Sainz de Aja J. , Garcia-de-Alba C. , Kim C. F. , Gomperts B. , Arumugaswami V. , Stripp B.R.
Published: June 2020

Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic resulting from zoonotic transmission of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Severe symptoms include viral pneumonia secondary to infection and inflammation of the lower respiratory tract, in some cases causing death. We developed primary human lung epithelial infection models to understand responses of proximal and distal lung epithelium to SARS-CoV-2 infection. Differentiated air-liquid interface cultures of proximal airway epithelium and 3D organoid cultures of alveolar epithelium were readily infected by SARS-CoV-2 leading to an epithelial cell-autonomous proinflammatory response. We validated the efficacy of selected candidate COVID-19 drugs confirming that Remdesivir strongly suppressed viral infection/replication. We provide a relevant platform for studying COVID-19 pathobiology and for rapid drug screening against SARS-CoV-2 and future emergent respiratory pathogens.

One Sentence Summary

A novel infection model of the adult human lung epithelium serves as a platform for COVID-19 studies and drug discovery.
Nicotinic receptors atlas in the adult human lung
Authors: Diabasana Zania , Perotin Jeanne-Marie , Belgacemi Randa , Ancel Julien , Mulette Pauline , Delepine Gonzague , Gosset Philippe , Maskos Uwe , Polette Myriam , Deslée Gaëtan , Dormoy Valérian
Published: June 2020

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels responsible for the rapid neural and neuromuscular signal transmission. Although it is well documented that 16 subunits are encoded by the human genome, their presence in airway epithelial cells (AEC) remains poorly understood, and contribution to pathology is mainly discussed in the context of cancer. We analysed nAChR subunit expression in the human lung of smokers and non-smokers using transcriptomic data for whole lung tissues, isolated large AEC, and isolated small AEC. We identified differential expressions of nAChRs in terms of detection and repartition in the three modalities. Smoking-associated alterations were also unveiled. Then, we identified a nAChR transcriptomic print at a single cell level. Finally, we reported the localizations of detectable nAChRs in bronchi and large bronchioles. Thus, we compiled the first complete atlas of pulmonary nAChRs to open new avenues to further unravel the involvement of these receptors in lung homeostasis and respiratory diseases.
The remarkable robustness of surrogate gradient learning for instilling complex function in spiking neural networks
Authors: Zenke Friedemann , Vogels Tim P.
Published: June 2020

Brains process information in spiking neural networks. Their intricate connections shape the diverse functions these networks perform. In comparison, the functional capabilities of models of spiking networks are still rudimentary. This shortcoming is mainly due to the lack of insight and practical algorithms to construct the necessary connectivity. Any such algorithm typically attempts to build networks by iteratively reducing the error compared to a desired output. But assigning credit to hidden units in multi-layered spiking networks has remained challenging due to the non-differentiable nonlinearity of spikes. To avoid this issue, one can employ surrogate gradients to discover the required connectivity in spiking network models. However, the choice of a surrogate is not unique, raising the question of how its implementation influences the effectiveness of the method. Here, we use numerical simulations to systematically study how essential design parameters of surrogate gradients impact learning performance on a range of classification problems. We show that surrogate gradient learning is robust to different shapes of underlying surrogate derivatives, but the choice of the derivative’s scale can substantially affect learning performance. When we combine surrogate gradients with a suitable activity regularization technique, robust information processing can be achieved in spiking networks even at the sparse activity limit. Our study provides a systematic account of the remarkable robustness of surrogate gradient learning and serves as a practical guide to model functional spiking neural networks.
Mechanistic modeling of vascular tumor growth: an extension of Biot’s theory to hierarchical bi-compartment porous medium system
Authors: Sciumè Giuseppe
Published: June 2020

Existing continuum multiphase tumor growth models typically do not include microvasculature, or if present, this is modeled as non-deformable. Vasculature behavior and blood flow are usually non-coupled with the underlying tumor phenomenology from the mechanical viewpoint; hence, phenomena as vessel compression/occlusion modifying microcirculation and oxygen supply cannot be taken into account.

The tumor tissue is here modeled as a reactive bi-compartment porous medium: the extracellular matrix constitutes the solid scaffold; blood is in the vascular porosity whereas the extra-vascular porous compartment is saturated by two cell phases and interstitial fluid (mixture of water and nutrient species). The pressure difference between blood and the extra-vascular overall pressure is sustained by vessel walls and drives shrinkage or dilatation of the vascular porosity. Model closure is achieved thanks to a consistent non-conventional definition of the Biot’s effective stress tensor.

Angiogenesis is modeled by introducing a vascularization state variable, and accounting for tumor angiogenic factors and endothelial cells. Closure relationships and mass exchange terms related to vessel formation are detailed in a numerical example reproducing the principal features of angiogenesis. This example is preceded by a first pedagogical numerical study on one-dimensional bio-consolidation. Results are exquisite to realize that the bi-compartment poromechanical model is fully coupled (the external loads impact fluid flow in both porous compartments) and to envision further applications as for instance modeling of drugs delivery and tissue ulceration.
A mobile genetic element in the SARS-CoV-2 genome is shared with multiple insect species
Authors: Tengs Torstein , Delwiche Charles F. , Jonassen Christine Monceyron
Published: June 2020

Unprecedented quantities of sequence data have been generated from the newly emergent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative agent of COVID-19. We document here the presence of s2m, a highly conserved, mobile genetic element with unknown function, in both the SARS-CoV-2 genome and a large number of insect genomes. Although s2m is not universally present among coronaviruses and appears to undergo horizontal transfer, the high sequence conservation and universal presence of s2m among isolates of SARS-CoV-2 indicate that, when present, the element is essential for viral function.
Tissue distribution of ACE2 protein in Syrian golden hamster (Mesocricetus auratus) and its possible implications in SARS-CoV-2 related studies
Authors: Suresh Voddu , Parida Deepti , Minz Aliva P. , Senapati Shantibhusan
Published: June 2020

Recently, the Syrian golden hamster (Mesocricetus auratus) has been demonstrated as a clinically relevant animal model for SARS-CoV-2 infection. However, lack of knowledge about the tissue-specific expression pattern of various proteins in these animals and the unavailability of reagents like antibodies against this species hampers optimal use of these models. The major objective of our current study was to analyze the tissue-specific expression pattern of angiotensin□converting enzyme 2 (ACE2), a proven functional receptor for SARS-CoV-2 in different organs of the hamster. We have adapted immunoblot analysis, immunohistochemistry, and immunofluorescence analysis techniques to evaluate the ACE2 expression pattern in different tissues of the Syrian golden hamster. We found that kidney, small intestine, esophagus, tongue, brain, and liver express ACE2. Epithelium of proximal tubules of kidney and surface epithelium of ileum expresses a very high amount of this protein. Surprisingly, analysis of stained tissue sections for ACE2 showed no detectable expression of ACE2 in the lung or tracheal epithelial cells. Similarly, all parts of the large intestine (caecum, colon, and rectum) were negative for ACE2 expression. Together, our findings corroborate some of the earlier reports related to ACE2 expression pattern in human tissues and also contradicts some others. We believe that the findings of this study will enable the appropriate use of the Syrian golden hamster to carryout SARS-CoV-2 related studies.
Manipulable object and human contact: preferences and modulation of emotional states in weaned piglets
Authors: Villain Avelyne S. , Lanthony Mathilde , Guérin Carole , Noûs Camille , Tallet Céline
Published: June 2020

1

Enriching the life of farm animals is an obligation in intensive farming conditions. In pigs, manipulable materials are mandatory when no bedding is available. Like manipulable objects, positive human interactions might be considered as enrichment, as they provide the animals occasions to interact, increase their activity and lead to positive emotional states. In this study, we investigated how weaned piglets perceived a manipulable object, and a familiar human. After a similar familiarization to both stimuli, twenty-four weaned piglets were tested for a potential preference for one of the stimuli and submitted to isolation/reunion tests to evaluate the emotional value of the stimuli. We hypothesized that being reunited with a stimulus would attenuate the stress of social isolation and promote positive behaviors, and even more that the stimulus has a positive emotional value for piglets. Although our behavioural data did not allow to show a preference for one of the stimuli, piglets approached more often the human and were observed laying down only near the human. Using behavioural and bioacoustic data, we showed that reunion with the human decreased more the time spent in an attentive state and mobility of piglets than reunion with the object, and isolation. Vocalizations differed between reunions with the object and the human, and were different from vocalizations during isolation. The human presence led to higher frequency range, more noisy and shorter grunts. Finally, both stimuli decreased the isolation stress of piglets, and piglets seemed to be in a more positive emotional state with the human compared to the object. It confirms the potential need for positive human interactions to be used as pseudo-social enrichment in pigs.
Replication stress and FOXM1 drive radiation induced genomic instability and cell transformation
Authors: Li Zhentian , Yu David S. , Doetsch Paul W. , Werner Erica
Published: June 2020

In contrast to the vast majority of research that has focused on the immediate effects of ionizing radiation, this work concentrates on the molecular mechanism driving delayed effects that emerge in the progeny of the exposed cells. We employed functional protein arrays to identify molecular changes induced in a human bronchial epithelial cell line (HBEC3-KT) and osteosarcoma cell line (U2OS) and evaluated their impact on outcomes associated with radiation induced genomic instability (RIGI) at day 5 and 7 post-exposure to a 2Gy X-ray dose, which revealed replication stress in the context of increased FOXM1 expression. Irradiated cells had reduced DNA replication rate detected by the DNA fiber assay and increased DNA resection detected by RPA foci and phosphorylation. Irradiated cells increased utilization of homologous recombination-dependent repair detected by a gene conversion assay and DNA damage at mitosis reflected by RPA positive chromosomal bridges, micronuclei formation and 53BP1 positive bodies in G1, all known outcomes of replication stress. Interference with the function of FOXM1, a transcription factor widely expressed in cancer, employing an aptamer, decreased radiation-induced micronuclei formation and cell transformation while plasmid-driven overexpression of FOXM1b was sufficient to induce replication stress, micronuclei formation and cell transformation.
TET1 interacts directly with NANOG via independent regions containing hydrophobic and aromatic residues
Authors: Pantier Raphaël , Mullin Nicholas , Hall-Ponsele Elisa , Chambers Ian
Published: June 2020

The DNA demethylase TET1 is highly expressed in embryonic stem cells. Knockout experiments indicate that TET1 is important for lineage commitment, and paradoxically, also for reprogramming to naïve pluripotency. TET1 binds to promoters through a CXXC domain which recognises unmethylated CpG dinucleotides. TET1 also binds to enhancers, presumably via interactions with partner proteins. The transcription factor NANOG interacts with TET1 and is predominantly localised at enhancers in ESCs. Therefore, NANOG may contribute to TET1 biological activity in pluripotent cells. However, the regions of TET1 involved in protein-protein interactions are mostly unknown. Here, we characterise the physical interaction between TET1 and NANOG using embryonic stem cells and bacterial expression systems. TET1 and NANOG interact through multiple binding sites that act independently. Critically, mutating conserved hydrophobic and aromatic residues within TET1 and NANOG abolishes the interaction. Comparative ChIP-seq analysis identifies genomic loci bound by both TET1 and NANOG, that correspond predominantly to pluripotency enhancers. Importantly, around half of NANOG transcriptional target genes are associated with TET1-NANOG co-bound sites. These results indicate a mechanism by which TET1 protein is targeted to specific sites of action at enhancers by direct interaction with a transcription factor.

Highlights

NANOG and TET1 have regulatory roles in maintaining and reprogramming pluripotency

TET1 and NANOG interact via multiple independent binding regions

TET1 and NANOG interactions are mediated by aromatic and hydrophobic residues

TET1 residues that bind NANOG are highly conserved in mammals

Co-localisation of TET1 and NANOG on chromatin is enriched at NANOG target genes
Diverse Epithelial Cell Populations Contribute to Regeneration of Secretory Units in Injured Salivary Glands
Authors: Ninche Ninche , Kwak Mingyu , Ghazizadeh Soosan
Published: June 2020

Salivary glands exert exocrine secretory function to provide saliva for lubrication and protection of the oral cavity. Its epithelium consists of several differentiated cell types including acinar, ductal and myoepithelial cells that are maintained in a lineage-restricted manner during homeostasis or after mild injuries. Glandular regeneration following a near complete loss of secretory cells, however, may involve cellular plasticity, although the mechanism and extent of such plasticity remain unclear. Here, by combining lineage-tracing experiments with a model of severe glandular injury in the mouse submandibular gland, we show thatde novoformation of secretory units involves induction of cellular plasticity in multiple non-acinar cell populations. Fate-mapping analysis revealed that although ductal stem cells marked by cytokeratin K14 and Axin2 undergo a multipotency switch, they do not make a significant contribution to acinar regeneration. Intriguingly, more than 80% of regenerated acini derive from differentiated cells including myoepithelial and ductal cells that dedifferentiate to a progenitor-like state before redifferentiation to acinar cells. The potential of diverse cell populations serving as a reserve source for acini widens the therapeutic options for hyposalivation.

Salivary glands rely in recruitment of committed and fully differentiated cell populations as well as stem cells to ensure rapid regeneration and recovery of secretory cells.
A single cellArabidopsisroot atlas reveals developmental trajectories in wild type and cell identity mutants
Authors: Shahan Rachel , Hsu Che-Wei , Nolan Trevor M. , Cole Benjamin J. , Taylor Isaiah W. , Vlot Anna Hendrika Cornelia , Benfey Philip N. , Ohler Uwe
Published: June 2020

Cell fate acquisition is a fundamental developmental process in all multicellular organisms. Yet, much is unknown regarding how a cell traverses the pathway from stem cell to terminal differentiation. Advances in single cell genomics1hold promise for unraveling developmental mechanisms2–3in tissues4, organs5–6, and organisms7–8. However, lineage tracing can be challenging for some tissues9and integration of high-quality datasets is often necessary to detect rare cell populations and developmental states10,11. Here, we harmonized single cell mRNA sequencing data from over 110,000 cells to construct a comprehensive atlas for a stereotypically developing organ with indeterminate growth, theArabidopsisroot. To test the utility of the atlas to interpret new datasets, we profiled mutants for two key transcriptional regulators at single cell resolution,shortrootandscarecrow. Although both transcription factors are required for early specification of cell identity12, our results suggest the existence of an alternative pathway acting in mature cells to specify endodermal identity, for whichSHORTROOTis required. Uncovering the architecture of this pathway will provide insight into specification and stabilization of the endodermis, a tissue analogous to the mammalian epithelium. Thus, the atlas is a pivotal advance for unraveling the transcriptional programs that specify and maintain cell identity to regulate organ development in space and time.
The transcriptome ofBalamuthia mandrillaristrophozoites for structure-based drug design
Authors: Phan Isabelle Q. , Rice Christopher A. , Craig Justin , Noorai Rooksana E. , McDonald Jacquelyn , Subramanian Sandhya , Tillery Logan , Barrett Lynn K. , Shankar Vijay , Morris James C. , Van Voorhis Wesley C. , Kyle Dennis E. , Myler Peter J.
Published: June 2020

Balamuthia mandrillaris, a pathogenic free-living amoeba (FLA), causes cutaneous skin lesions as well as the brain-eating disease:Balamuthiagranulomatous amoebic encephalitis (GAE). These diseases, and diseases caused by other pathogenic FLA,Naegleria fowleriorAcanthamoebaspecies, are minimally studied from a drug discovery perspective; few targets have been validated or characterized at the molecular level, and little is known about the biochemical pathways necessary for parasite survival. Chemotherapies for CNS disease caused byB. mandrillarisrequire vast improvement. Current therapeutics are limited to a small number of drugs that were previously discovered in the last century throughin vitrotesting or identified after use in the small pool of surviving reports.

Using our recently published methodology to identify potentially useful therapeutics, we screened a collection of 85 compounds that have previously been reported to have antiparasitic activity. We identified 59 compounds that impacted growth at concentrations below 220 μM. Since there is no fully annotated genome or proteome, we used RNA-Seq to reconstruct the transcriptome ofB. mandrillarisand locate the coding sequences of the specific genes potentially targeted by the compounds identified to inhibit trophozoite growth. We determined the sequence of 17 of these target genes and obtained expression clones for 15 that we validated by direct sequencing.
Increased serum peripheral C-reactive protein is associated with reduced small-molecule brain perfusion in healthy volunteers and subjects with major depressive disorder
Authors: Turkheimer Federico E. , Althubaity Noha , Schubert Julia , Nettis Maria A. , Cousins Oliver , Dima Danai , Mondelli Valeria , Bullmore Edward T. , Pariante Carmine , Veronese Mattia
Published: June 2020

The relationship between peripheral and central immunity and how these ultimately may cause depressed behaviour has been the focus of a number of imaging studies conducted with Positron Emission Tomography (PET). These studies aimed at testing the immune-mediated model of depression that proposes a direct effect of peripheral cytokines and immune cells on the brain to elicit a neuroinflammatory response via a leaky blood-brain barrier and ultimately depressive behaviour. However, studies conducted so far using PET radioligands targeting the neuroinflammatory marker 18 kDa translocator protein (TSPO) in patient cohorts with depression have demonstrated mild inflammatory brain status but no correlation between central and peripheral immunity.

To gain a better insight into the relationship between heightened peripheral immunity and neuroinflammation, we estimated blood-to-brain and blood-to-CSF perfusion rates for two TSPO radiotracers collected in two separate studies, one large cross-sectional study of neuroinflammation in normal and depressed cohorts and a second study where peripheral inflammation in healthy controls was induced via subcutaneous injection of interferon (IFN)-α. In both studies we observed a consistent negative association between peripheral inflammation, measured with c-reactive protein P (CRP), and radiotracer perfusion into and from the brain parenchyma and CSF. Importantly, there was no association of this effect with the marker of BBB leakage S100β, that was unchanged, but there was an association between the reduction of tracer perfusion in volunteers injected with interferon (IFN)-α and VEGF, a potent vascular permeability factor.

These results support a different model of peripheral-to-central immunity interaction whereas peripheral inflammation causes a “stiffening” of the healthy BBB with consequent reduction of small molecule trafficking to and from the blood into the brain and CSF. This effect, on the long term, is likely to disrupt brain homeostasis and induce depressive behavioural symptoms. Moreover, given the molecular similarity between the TSPO ligands and antidepressant, this phenomenon may underlie treatment resistance in depressive cohorts with heightened peripheral status.
Assessment of a Diagnostic Strategy Based on Chest Computed Tomography in Patients Hospitalized for COVID-19 Pneumonia: an observational study
Authors: Thieux Marine , Kalenderian Anne-Charlotte , Chabrol Aurélie , Gendt Laurent , Giraudier Emma , Lelievre Hervé , Lounis Samir , Mataix Yves , Moderni Emeline , Paradisi Laetitia , Ranchon Guillaume , Khoury Carlos El
Published: June 2020

Objectives

To assess the relevance of a diagnostic strategy for COVID-19 based on chest computed tomography (CT) in patients with hospitalization criteria.

Setting

Observational study with retrospective analysis in a French emergency department (ED).

Participants and intervention

From March 3 to April 2, 2020, 385 adult patients presenting to the ED for suspected COVID-19 underwent an evaluation that included history, physical examination, blood tests, real-time reverse transcription-polymerase chain reaction (RT-PCR) and chest CT. When the time-interval between chest CT and RT-PCR assays was longer than 7 days, patients were excluded from the study. Only patients with hospitalization criteria were included. Diagnosis accuracy was assessed using the sensitivity and specificity of RT-PCR.

Outcomes

Sensitivity and specificity of RT-PCR, chest CT (also accompanied by lymphopenia) were measured and were also analyzed by subgroups of age and sex.

Results

Among 377 included subjects, RT-PCR was positive in 36%, while chest CT was compatible with a COVID-19 diagnosis in 59%. In the population with positive RT-PCR, there were more men (55% vs 37%, p=0.015), a higher frequency of reticular and, or, interlobular septal thickening (53% vs 31%, p=0.02) as well as a higher frequency of bilateral lesion distribution (98% vs 86%, p=0.01) compared to the population with negative RT-PCR. The proportion of lymphopenia was higher in men vs women (47% vs 39%, p=0.03) and varies between patients >80 versus 50-80 and p<0.001).

Using CT as reference, RT-PCR obtained a sensitivity of 61%, specificity of 93%. There was a significant difference between CT and RT-PCR diagnosis performance (p<0.001). When CT was accompanied by lymphopenia, sensitivity and specificity of RT-PCR were respectively 71% and 94%. CT abnormalities and lymphopenia provided diagnosis in 29% of patients with negative PCR.

Conclusions

Chest CT had a superior yield than RT-PCR in COVID-19 hospitalized patients, especially when accompanied by lymphopenia.
Multiple Myeloma and SARS-CoV-2 Infection: Clinical Characteristics and Prognostic Factors of Inpatient Mortality
Authors: Martínez-López Joaquín , Mateos María-Victoria , Encinas Cristina , Sureda Anna , Hernández-Rivas José Ángel , López de la Guía Ana , Conde Diego , Krsnik Isabel , Prieto Elena , Grau Rosalía Riaza , Gironella Mercedes , Blanchard María Jesús , Caminos Nerea , Fernández de Larrea Carlos , Alicia Senin María , Escalante Fernando , de la Puerta José Enrique , Giménez Eugenio , Martínez-Barranco Pilar , José Mateos Juan , Casado Luis Felipe , Bladé Joan , José Lahuerta Juan , De la Cruz Javier , San-Miguel Jesús
Published: June 2020

There is limited information on the characteristics, pre-admission prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with coronavirus disease 2019 (COVID-19). This retrospective case series investigated characteristics and outcomes of 167 MM patients hospitalized with COVID-19 reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in Spain between March 1 and April 30, 2020. Outcomes were compared with a randomly selected contemporary cohort of 167 age-/sex-matched non-cancer patients with COVID-19 admitted at 6 participating hospitals. Common demographic, clinical, laboratory, treatment, and outcome variables were collected; specific disease status and treatment data were collected for MM patients. Among the MM and non-cancer patients, median age was 71 years and 57% of patients were male in each series, and 75% and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate-severe in 77% and 89% of patients and critical in 8% and 4%, respectively. Supplemental oxygen was required by 47% and 55% of MM and non-cancer patients, respectively, and 21%/9% vs 8%/6% required non-invasive/invasive ventilation. Inpatient mortality was 34% and 23% in MM and non-cancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors of inpatient mortality on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19.

Key Points

There is an increased risk of inpatient mortality (34% vs 23%) in MM vs age-/sex-matched non-cancer patients hospitalized with COVID-19.

Adverse prognostic factors at admission for inpatient mortality in MM patients include age >65 y, male sex, renal disease, and active MM.
Findings and prognostic value of lung ultrasound in COVID-19 pneumonia
Authors: Castelao Jorge , Graziani Desirée ,   Collaborative Working Group COVID Pulmonology Guadalajara, Soriano Joan B. , Izquierdo José Luis
Published: June 2020

Objectives

The aim is to systematically describe the findings of lung ultrasound in patients with COVID-19 pneumonia and to analyze its prognostic value.

Methods

Lung ultrasound was performed to 63 patients with COVID-19 pneumonia admitted to a University Hospital. Lung involvement was evaluated using a 4-point scale with a 12-area pulmonary division (lung score -LS-). Ultrasound findings, along with clinical characteristics, were recorded.

Results

All patients showed ultrasound involvement in at least 1 area (mean 8 ± 3.5). Total LS was 15.3 ± 8.1, without differences between left and right lung. Most affected regions were the lower one (95.2%) and the posterior one (73.8%). Total LS showed a strong correlation (r = -0.765) with PaO2/FiO2; by lung regions, those with a higher correlation were the LS of the anterior one (r = -0.823) and the LS of the upper one (r = -0.731). 22.2% of patients required non-invasive respiratory support (NIRS). Multivariate analysis shows that anterior region LS, adjusted for age and sex, is significant (odds ratio 2.159, 95% confidence interval 1.309 to 3.561) for the risk of requiring NIRS. Anterior region LS ≥ 4 and total LS ≥19 have similar characteristics to predict the need for NIRS.

Conclusions

Ultrasound involvement in COVID-19 pneumonia is bilateral and heterogeneous. Most affected regions are the posterior and the lower ones. The anterior region has prognostic value, because its involvement strongly correlates with the risk of requiring NIRS, and an anterior region LS ≥ 4 has high sensitivity and specificity for predicting the need for NIRS.
Evidence for structural protein damage and membrane lipid remodeling in red blood cells from COVID-19 patients
Authors: Thomas Tiffany , Stefanoni Davide , Dzieciatkowska Monika , Issaian Aaron , Nemkov Travis , Hill Ryan C. , Francis Richard O , Hudson Krystalyn E. , Buehler Paul W. , Zimring James C. , Hod Eldad A. , Hansen Kirk C. , Spitalnik Steven L. , D’Alessandro Angelo
Published: June 2020

The SARS-CoV-2 beta coronavirus is the etiological driver of COVID-19 disease, which is primarily characterized by shortness of breath, persistent dry cough, and fever. Because they transport oxygen, red blood cells (RBCs) may play a role in the severity of hypoxemia in COVID-19 patients.

The present study combines state-of-the-art metabolomics, proteomics, and lipidomics approaches to investigate the impact of COVID-19 on RBCs from 23 healthy subjects and 29 molecularly-diagnosed COVID-19 patients. RBCs from COVID-19 patients had increased levels of glycolytic intermediates, accompanied by oxidation and fragmentation of ankyrin, spectrin beta, and the N-terminal cytosolic domain of band 3 (AE1). Significantly altered lipid metabolism was also observed, especially short and medium chain saturated fatty acids, acyl-carnitines, and sphingolipids. Nonetheless, there were no alterations of clinical hematological parameters, such as RBC count, hematocrit, and mean corpuscular hemoglobin concentration, with only minor increases in mean corpuscular volume. Taken together, these results suggest a significant impact of SARS-CoV-2 infection on RBC structural membrane homeostasis at the protein and lipid levels. Increases in RBC glycolytic metabolites are consistent with a theoretically improved capacity of hemoglobin to off-load oxygen as a function of allosteric modulation by high-energy phosphate compounds, perhaps to counteract COVID-19-induced hypoxia. Conversely, because the N-terminus of AE1 stabilizes deoxyhemoglobin and finely tunes oxygen off-loading, RBCs from COVID-19 patients may be incapable of responding to environmental variations in hemoglobin oxygen saturation when traveling from the lungs to peripheral capillaries and, as such, may have a compromised capacity to transport and deliver oxygen.

Graphical Abstract

Key Points

COVID-19 promotes oxidation and fragmentation of membrane proteins, including the N-term of band 3

RBCs from COVID-19 patients are characterized by increases in glycolysis and altered lipidomes

COVID-19 impacts two critical mechanisms that finely tune red cell membranes and hemoglobin oxygen affinity
Synthesis and crystal structures of 2-(ferrocenylcarbonyl)benzoic acid and 3-ferrocenylphthalide
Authors: Pokharel Uttam R. , Bergeron Jonathan T. , Fronczek Frank R.
Published: June 2020

The title compounds, 2-(ferrocenylcarbonyl)benzoic acid, [Fe(C5H5)(C13H9O3)], 1, and 3-ferrocenylphthalide [systematic name: 3-ferrocenyl-2-benzofuran-1(3H)-one], [Fe(C5H5)(C13H9O2)], 2, have been synthesized and structurally characterized by single-crystal X-ray diffraction. The crystal structure of compound 1 was solved recently at room temperature [Qin, Y. (2019). CSD Communication (CCDC deposition number 1912662). CCDC, Cambridge, England]. Here we report a redetermination of its crystal structure at 90 K with improved precision by a factor of about three. The molecular structures of both compounds exhibit a typical sandwich structure. In the crystal packing of compound 1, each molecule engages in intermolecular hydrogen bonding, forming a centrosymmetric dimer with graph-set notation R
2
2 (8) and an O...O distance of 2.6073 (15) Å. There are weak C—H...O and C—H...π interactions in the crystal packing of compound 2. The phthalide moiety in 2 is oriented roughly perpendicular to the ferrocene backbone, with a dihedral angle of 77.4 (2)°.
Structure of apo flavin-dependent halogenase Xcc4156 hints at a reason for cofactor-soaking difficulties
Authors: Widmann Christiane , Ismail Mohamed , Sewald Norbert , Niemann Hartmut H.
Published: June 2020

Flavin-dependent halogenases regioselectively introduce halide substituents into electron-rich substrates under mild reaction conditions. For the enzyme Xcc4156 fromXanthomonas campestris, the structure of a complex with the cofactor flavin adenine dinucleotide (FAD) and a bromide ion would be of particular interest as this enzyme exclusively brominates model substratesin vitro. Apo Xcc4156 crystals diffracted to 1.6 Å resolution. The structure revealed an open substrate-binding site lacking the loop regions that close off the active site and contribute to substrate binding in tryptophan halogenases. Therefore, Xcc4156 might accept larger substrates, possibly even peptides. Soaking of apo Xcc4156 crystals with FAD led to crumbling of the intergrown crystals. Around half of the crystals soaked with FAD did not diffract, while in the others there was no electron density for FAD. The FAD-binding loop, which changes its conformation between the apo and the FAD-bound form in related enzymes, is involved in a crystal contact in the apo Xcc4156 crystals. The conformational change that is predicted to occur upon FAD binding would disrupt this crystal contact, providing a likely explanation for the destruction of the apo crystals in the presence of FAD. Soaking with only bromide did not result in bromide bound to the catalytic halide-binding site. Simultaneous soaking with FAD and bromide damaged the crystals more severely than soaking with only FAD. Together, these latter two observations suggest that FAD and bromide bind to Xcc4156 with positive cooperativity. Thus, apo Xcc4156 crystals provide functional insight into FAD and bromide binding, even though neither the cofactor nor the halide is visible in the structure.
A hybrid constriction coefficient-based particle swarm optimization and gravitational search algorithm for training multi-layer perceptron
Authors: Rather Sajad Ahmad , Bala P. Shanthi
Published: June 2020

Purpose

In this paper, a newly proposed hybridization algorithm namely constriction coefficient-based particle swarm optimization and gravitational search algorithm (CPSOGSA) has been employed for training MLP to overcome sensitivity to initialization, premature convergence, and stagnation in local optima problems of MLP.

Design/methodology/approach

In this study, the exploration of the search space is carried out by gravitational search algorithm (GSA) and optimization of candidate solutions, i.e. exploitation is performed by particle swarm optimization (PSO). For training the multi-layer perceptron (MLP), CPSOGSA uses sigmoid fitness function for finding the proper combination of connection weights and neural biases to minimize the error. Secondly, a matrix encoding strategy is utilized for providing one to one correspondence between weights and biases of MLP and agents of CPSOGSA.

Findings

The experimental findings convey that CPSOGSA is a better MLP trainer as compared to other stochastic algorithms because it provides superior results in terms of resolving stagnation in local optima and convergence speed problems. Besides, it gives the best results for breast cancer, heart, sine function and sigmoid function datasets as compared to other participating algorithms. Moreover, CPSOGSA also provides very competitive results for other datasets.

Originality/value

The CPSOGSA performed effectively in overcoming stagnation in local optima problem and increasing the overall convergence speed of MLP. Basically, CPSOGSA is a hybrid optimization algorithm which has powerful characteristics of global exploration capability and high local exploitation power. In the research literature, a little work is available where CPSO and GSA have been utilized for training MLP. The only related research paper was given by Mirjalili et al., in 2012. They have used standard PSO and GSA for training simple FNNs. However, the work employed only three datasets and used the MSE performance metric for evaluating the efficiency of the algorithms. In this paper, eight different standard datasets and five performance metrics have been utilized for investigating the efficiency of CPSOGSA in training MLPs. In addition, a non-parametric pair-wise statistical test namely the Wilcoxon rank-sum test has been carried out at a 5% significance level to statistically validate the simulation results. Besides, eight state-of-the-art meta-heuristic algorithms were employed for comparative analysis of the experimental results to further raise the authenticity of the experimental setup.
The role of agency costs in the voluntary adoption of XBRL-based financial reporting
Authors: De Martinis Michael , Khedmati Mehdi , Navissi Farshid , Sualihu Mohammed Aminu , Tofik-Abu Zakiya
Published: June 2020

Purpose

The purpose of this paper is to examine whether and how firm's agency costs played a role in the voluntary adoption of the eXtensible Business Reporting Language (XBRL) under the SEC's voluntary filing program (VFP) that encouraged the voluntary adoption of the XBRL.

Design/methodology/approach

This study employs a logistics regression and a sample of 140 firms that voluntarily participated in the VFP during its entire existence in the United States, and 140 matched-pair counterparts that did not voluntarily adopt the XBRL to investigate the role of agency costs in the voluntary adoption of XBRL-based financial reporting.

Findings

We find evidence consistent with the conjecture that a firm's low magnitude of agency costs plays a significant motivating role in the voluntary adoption of XBRL-based financial reporting. Our results continue to hold after using an alternative measure of agency costs and conducting two-stage least squares regressions. Supplementing these results, the study also shows that the level of agency costs of voluntary XBRL adopters remains statistically unchanged after the adoption while the level of agency costs associated with the firms that did not participate in SEC's VFP significantly decline after the adoption during the XBRL mandate.

Practical implications

The findings of this study suggest that based on a firm's level of agency costs, regulators and policymakers, especially those in countries that are yet to mandate XBRL reporting, can, in advance, identify firms that are more likely to comply with their new financial reporting initiatives.

Originality/value

This paper provides first evidence on the role of agency costs in the voluntary adoption of XBRL using data from the United States.
Handicaps and new opportunity businesses: what do we (not) know about disabled entrepreneurs?
Authors: Mota Irisalva , Marques Carla , Sacramento Octávio
Published: June 2020

Purpose

The process by which disabled individuals become entrepreneurs can be influenced by factors of different orders. Throughout their entrepreneurship careers and projects, disabled entrepreneurs may have to overcome multiple personal, social and political barriers. This study aims to review what we do (and do not) know about disabled entrepreneurs research to date.

Design/methodology/approach

The literature review focused on analyzing 42 articles from two databases, namely, Web of Science and Scopus. After the articles were selected, they were grouped into thematic clusters.

Findings

The results were categorized into four areas, namely, entrepreneurs with disabilities, self-employment as an alternative to unemployment for people with disabilities, barriers faced by disabled entrepreneurs and the importance of education, training and/or orientation for these individuals’ entrepreneurship. The research verified that, in some cases, people with disabilities resort to self-employment and become entrepreneurs to avoid unemployment. Education and training’s positive role in how this process develops is clear as they empower individuals with disabilities and enable them to raise entrepreneurial attitudes.

Originality/value

Based on the citation profile of articles on disabled entrepreneurs, the results contribute to a better understanding of the flow and main findings of scientific research on this topic over the past 15 years. The findings also include research tendencies that reveal the field’s emergent perspectives, which are of great importance to academics seeking to enhance entrepreneurial processes and policymakers interested in stimulating entrepreneurship education.
God in the marketplace: Pentecostalism and marketing ritualization among Black Africans in the UK
Authors: Ojo Sanya , Nwankwo Sonny
Published: June 2020

Purpose

This paper aims to examine market-mediated transformative capacities of Black African Pentecostalism. It does this by exploring the interface between religion, culture and identity to generate a fresh interpretation of how marketing is ritualized among UK’s Black Africans on the platform of Pentecostalism.

Design/methodology/approach

Methodology is based on in-depth interviews with respondents drawn from the African Pentecostal movements in London, UK. This paper shows how adherents’ responsiveness to Pentecostal dogmas generated market advantages.

Findings

The paper reveals the interconnectedness of religion, faith and culture which, in turn, coalesced into a dense network that defines the reproduction, organization and approach to entrepreneurial marketing.

Originality/value

Pentecostal practices unveil the marketing notion of “Pentepreneurship”, which combines both spiritual and enterprise activities to formulate a fused space of engagement straddling the sacred and the secular. This fusion points to a unique platform of entrepreneurial marketing that bestrides ethno-cultural, religious and economic identities.
Commercial social spaces in the post-disaster context
Authors: Haeffele Stefanie , Craig Alexander Wade
Published: June 2020

Purpose

This paper argues that commercial entrepreneurial activities have social implications and can provide needed social spaces during the disaster recovery process, and that viewing commercial enterprises as socially valuable has implications for post-disaster public policy.

Design/methodology/approach

This paper discusses themes and concepts developed through in-depth interviews conducted in New Orleans, Louisiana, and Houston, Texas, after Hurricane Katrina. Particular case studies of the personal experiences of communities that recovered after Hurricane Katrina are utilized to highlight how commercial entrepreneurship creates and maintains social spaces where community members can share resources and connect during the recovery process.

Findings

Entrepreneurs need not have a specific social mission in order to make social contributions, and commercial entrepreneurship should create and maintain social spaces that are important for community recovery after disasters.

Practical implications

The social spaces that commercial entrepreneurs facilitate should be considered when designing and implementing public policy in the post-disaster context. Policies can often hinder recovery, and policymakers should instead establish clear regulatory regimes and allow for greater space for entrepreneurs to act.

Originality/value

This paper highlights the role entrepreneurs play in advancing social goals and purposes after disasters, specifically how commercial entrepreneurs can create and maintain social spaces where community members gather to discuss their challenges and strategies for disaster recovery. It highlights the extra-economic role of commercial entrepreneurs and discusses the implications for public policy based on this broadened conception of entrepreneurship.