bluuebunny/crossref_metadata_2025 huggingface dataset:
A multi-scale investigation of the human communication system's response to visual disruption
Authors: Trujillo James P. , Levinson Stephen C. , Holler Judith
Published: April 2022

In human communication, when the speech is disrupted, the visual channel (e.g. manual gestures) can compensate to ensure successful communication. Whether speech also compensates when the visual channel is disrupted is an open question, and one that significantly bears on the status of the gestural modality. We test whether gesture and speech are dynamically co-adapted to meet communicative needs. To this end, we parametrically reduce visibility during casual conversational interaction and measure the effects on speakers' communicative behaviour using motion tracking and manual annotation for kinematic and acoustic analyses. We found that visual signalling effort was flexibly adapted in response to a decrease in visual quality (especially motion energy, gesture rate, size, velocity and hold-time). Interestingly, speech was also affected: speech intensity increased in response to reduced visual quality (particularly in speech-gesture utterances, but independently of kinematics). Our findings highlight that multi-modal communicative behaviours are flexibly adapted at multiple scales of measurement and question the notion that gesture plays an inferior role to speech.
Structural analysis of mixed α- and β-amyrin samples
Authors: Gómez-Pulido Luz D. M. , González-Cano Rafael C. , Benítez José J. , Domínguez Eva , Heredia Antonio
Published: April 2022

Little is known about the structure and molecular arrangement of α- and β-amyrin, a class of triterpenoids found within the cuticle of higher plants. Blends of both amyrin isomers with different ratios have been studied taking into consideration a combined methodology of density functional theory (DFT) calculations with experimental data from scanning electron microscopy, differential scanning calorimetry and Raman vibrational spectroscopy. Results indicate that trigonal trimeric aggregations of isomer mixtures are more stable, especially in the 1 : 2 (
α
:
β
) ratio. A combination of Raman spectroscopy and DFT calculations has allowed to develop an equation to determine the amount of β-amyrin in a mixed sample.
Targeting the PD-1/PD-L1 axis for cancer treatment: a review on nanotechnology
Authors: Tran Tuan Hiep , Phuong Tran Thi Thu
Published: April 2022

Although nanomedicines have been in the oncology field for almost three decades with the introduction of doxil, only a few nanomedicine products have reached approval. Can nanotechnology be a realistic tool to reduce the number of hospital beds? At present, several clinically approved anti-PD-1/PD-L1 antibodies or CAR T cell-based therapies are available; however, the immunotherapy field is far from mature. Will immunotherapy be the fourth pillar of cancer treatment? In this review, we summarized the current status of immunotherapy using PD-1/PD-L1-targeting nanocarriers. The knowledge on material science, therapeutic agents and formulation designs could pave the way for high-efficacy treatment outcomes.
Testing macroecological theories in cryptocurrency market: neutral models cannot describe diversity patterns and their variation
Authors: Brigatti Edgardo , Amazonas Mendes Estevan Augusto
Published: April 2022

We develop an analysis of the cryptocurrency market borrowing methods and concepts from ecology. This approach makes it possible to identify specific diversity patterns and their variation, in close analogy with ecological systems, and to characterize the cryptocurrency market in an effective way. At the same time, it shows how non-biological systems can have an important role in contrasting different ecological theories and in testing the use of neutral models. The study of the cryptocurrencies abundance distribution and the evolution of the community structure strongly indicates that these statistical patterns are not consistent with neutrality. In particular, the necessity to increase the temporal change in community composition when the number of cryptocurrencies grows, suggests that their interactions are not necessarily weak. The analysis of the intraspecific and interspecific interdependency supports this fact and demonstrates the presence of a market sector influenced by mutualistic relations. These latest findings challenge the hypothesis of weakly interacting symmetric species, the postulate at the heart of neutral models.
Immune Correlates Analysis of a Single Ad26.COV2.S Dose in the ENSEMBLE COVID-19 Vaccine Efficacy Clinical Trial
Authors: Fong Youyi , McDermott Adrian B. , Benkeser David , Roels Sanne , Stieh Daniel J. , Vandebosch An , Gars Mathieu Le , Van Roey Griet A. , Houchens Christopher R. , Martins Karen , Jayashankar Lakshmi , Castellino Flora , Amoa-Awua Obrimpong , Basappa Manjula , Flach Britta , Lin Bob C. , Moore Christopher , Naisan Mursal , Naqvi Muhammed , Narpala Sandeep , O’Connell Sarah , Mueller Allen , Serebryannyy Leo , Castro Mike , Wang Jennifer , Petropoulos Christos J. , Luedtke Alex , Hyrien Ollivier , Lu Yiwen , Yu Chenchen , Borate Bhavesh , van der Laan Lars W. P. , Hejazi Nima S. , Kenny Avi , Carone Marco , Wolfe Daniel N. , Sadoff Jerald , Gray Glenda E. , Grinsztejn Beatriz , Goepfert Paul A. , Little Susan J. , Paiva de Sousa Leonardo , Maboa Rebone , Randhawa April K. , Andrasik Michele P. , Hendriks Jenny , Truyers Carla , Struyf Frank , Schuitemaker Hanneke , Douoguih Macaya , Kublin James G. , Corey Lawrence , Neuzil Kathleen M. , Carpp Lindsay N. , Follmann Dean , Gilbert Peter B. , Koup Richard A. , Donis Ruben O. ,   the Janssen Team,   the Coronavirus Vaccine Prevention Network (CoVPN)/ENSEMBLE Team,   the United States Government (USG)/CoVPN Biostatistics Team
Published: April 2022

Anti-spike IgG binding antibody, anti-receptor binding domain IgG antibody, and pseudovirus neutralizing antibody measurements four weeks post-vaccination were assessed as correlates of risk of moderate to severe-critical COVID-19 outcomes through 83 days post-vaccination and as correlates of protection following a single dose of Ad26.COV2.S COVID-19 vaccine in the placebo-controlled phase of ENSEMBLE, an international, randomized efficacy trial. Each marker had evidence as a correlate of risk and of protection, with strongest evidence for 50% inhibitory dilution (ID50) neutralizing antibody titer. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; p=0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43, 72%) at nonquantifiable ID50 (< 2.7 IU50/ml) and rose to 89% (78, 96%) at ID50 = 96.3 IU50/ml. Comparison of the vaccine efficacy by ID50 titer curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine, and the COV002-UK trial of the AZD1222 vaccine supported consistency of the ID50 titer correlate of protection across trials and vaccine types.
XGBoost, a novel explainable AI technique, in the prediction of myocardial infarction, a UK Biobank cohort study
Authors: Moore Alexander , Bell Max
Published: April 2022

Background and objective

Myocardial infarction is common and associated with high morbidity and mortality. This study assessed if “Explainable AI” in the form of extreme gradient boosting (XGBoost) could outperform traditional logistic regression in predicting myocardial infarction (MI) in a large cohort.

Methods

We compared two machine learning methods, XGBoost and logistic regression in predicting risk of MI. The UK Biobank is a population-based prospective cohort including 502 506 volunteers with active consent, aged 40–69 years at recruitment from 2006 to 2010. These subjects were followed until end of 2019 and the primary outcome was myocardial infarction.

Results

Both models were trained using 90% of the cohort. The remaining 10% was used as a test set. Both models were equally precise, but the regression model classified more of the healthy class correctly. XGBoost was more accurate in identifying individuals who later suffered a myocardial infarction. Receiver operator characteristic (ROC) scores are class size invariant. In this metric XGBoost outperformed the logistic regression model, with ROC scores of 0.86 (accuracy 0.75; precision 0.99 and recall 0.75 for the healthy class; precision 0.07 and recall 0.81 for the MI-class) compared to 0.77 (accuracy 0.77; precision 0.99 and recall 0.77 for the healthy class; precision 0.07 and recall 0.78). Secondly, we demonstrate how SHAPley values can be used to visualize and interpret the predictions made by XGBoost models, both for the cohort test set and for individuals.

Conclusions

The XGBoost machine learning model shows very promising results in evaluating risk of MI in a large and diverse population. This model can be used, and visualized, both for individual assessments and in larger cohorts. The predictions made by the XGBoost models, points towards a future where “Explainable AI” may help to bridge the gap between medicine and data science.
The Brain Reacting to COVID-19: Analysis of the Cerebrospinal Fluid and Serum Proteome,Transcriptome and Inflammatory Proteins
Authors: Reinhold Dirk , Farztdinov Vadim , Yan Yan , Meisel Christian , Sadlowski Henrik , Kühn Joachim , Perschel Frank H. , Endres Mathias , Düzel Emrah , Vielhaber Stefan , Guttek Karina , Goihl Alexander , Venø Morten , Teegen Bianca , Stöcker Winfried , Stubbemann Paula , Kurth Florian , Sander Leif E. , Ralser Markus , Otto Carolin , Streit Simon , Jarius Sven , Ruprecht Klemens , Radbruch Helena , Kjems Jørgen , Mülleder Michael , Heppner Frank , Körtvelyessy Peter
Published: April 2022

Patients with COVID-19 can have a variety of neurological symptoms, but the pathomechanism of CNS involvement in COVD-19 remains unclear. While routine cerebrospinal fluid (CSF) analyses in patients with neurological manifestations of COVID-19 generally show no or only mild inflammation, more detailed data on inflammatory mediators in the CSF of patients with COVID-19 are scarce.

Here, we used mass spectrometry to study the proteome, Enzym-linkend immunoassays, semiquantitative cytokine arrays, autoantibody screening, and RNA profiling to study the neuroinflammation. We study the inflammatory response in paired CSF and serum samples of patients with COVID-19 (n=38). Patients with herpes simplex virus encephalitis (HSVE, n=10) and patients with non-inflammatory, non-neurodegenerative neurological diseases (n=28) served as controls. Proteomics on single protein level and subsequent pathway analysis showed similar yet strongly attenuated inflammatory changes in the CSF of COVID-19 patients compared to HSVE patients. CSF/serum indices of interleukin-6, interleukin-16 and CXCL10 together point at an origin from these inflammatory proteins from outside the central nervous system. When stratifying COVID-19 patients into those with and without bacterial superinfection as indicated by elevated procalcitonin levels, inflammatory markers were significantly higher in those with concomitant bacterial superinfection. RNA sequencing in the CSF revealed 101 linear RNAs comprising messenger RNAs, micro RNAs and t-RNA fragments being significantly differentially expressed in COVID-19 than in HSVE or controls.

Our findings may explain the absence of signs of intrathecal inflammation upon routine CSF testing despite the presence of SARS-CoV2 infection-associated neurological symptoms. The relevance of blood-derived mediators of inflammation in the CSF for neurological post-COVID-19 symptoms deserves further investigation.
Larger and more dentated hippocampal structure is associated with better memory in the oldest-old
Authors: Parpura Vuga , Caceres Hector S , Sims Sara A , Ver Hoef Lawrence , Ramaniharan Anandh K , Merritt Stacy , Rezaei Roxanne F , Bharadwaj Pradyumna K , Franchetti Mary Kate , Raichlen David A , Jessup Courtney J , Hishaw Alex G , Van Etten Emily J , Trouard Theodore P , Geldmacher David S , Wadley Virginia G , Alperin Noam , Porges Eric S , Woods Adam J , Cohen Ron A , Levin Bonnie E , Rundek Tatjana , Alexander Gene E , Visscher Kristina M
Published: April 2022

Episodic memory is widely recognized as a critically important aspect of cognition that is often impacted by cognitive and brain aging. Prior work has shown that episodic memory is related to the presence of teeth-like folds on the dentate gyrus, called dentation. We hypothesized that episodic memory performance relates to overall hippocampal structure (i.e., dentation and volume) in an oldest-old cohort. We used data from the McKnight Brain Aging Registry, which consisted of cognitively healthy 85+-year-old adults. We conducted a canonical correlation analysis on 111 participants between a set of episodic memory tests and a set of characterizations of hippocampal structure. The analysis yielded a strong canonical correlation between episodic memory and hippocampal structure (r = 0.491, p = <0.001). The results suggest there is a connection between hippocampal morphology and function in the oldest-old. Our findings suggest that dentation may play an important role in relation to the individual differences observed in episodic memory performance among the oldest old and that hippocampal structure supports healthy cognitive aging.

Highlights

We characterized hippocampal dentation in a healthy oldest-old sample.

Hippocampal structure is related to episodic memory in healthy oldest-old adults.

Memory functioning is related to both hippocampal volume and dentation.
DeepPerVar: a multimodal deep learning framework for functional interpretation of genetic variants in personal genome
Authors: Wang Ye , Chen Li
Published: April 2022

Motivation

Understanding the functional consequence of genetic variants, especially the noncoding ones, is important but particularly challenging. Genome-wide association studies or quantitative trait locus analyses may be subject to limited statistical power and linkage disequilibrium, and thus are less optimal to pinpoint the causal variants. Moreover, most existing machine learning approaches, which exploit the functional annotations to interpret and prioritize putative causal variants, cannot accommodate the heterogeneity of personal genetic variations and traits in a population study, targeting a specific disease.

Results

By leveraging paired whole genome sequencing data and epigenetic functional assays in a population study, we propose a multi-modal deep learning framework to predict genome-wide quantitative epigenetic signals by considering both personal genetic variations and traits. The proposed approach can further evaluate the functional consequence of noncoding variants on an individual level by quantifying the allelic difference of predicted epigenetic signals. By applying the approach to the ROSMAP cohort studying Alzheimer’s disease (AD), we demonstrate that the proposed approach can accurately predict quantitative genome-wide epigenetic signals and in key genomic regions of AD causal genes, learn canonical motifs reported to regulate gene expression of AD causal genes, improve the partitioning heritability analysis, and prioritize putative causal variants in a GWAS risk locus. Finally, we release the proposed deep learning model as a stand-alone Python toolkit and a web server.

Availability

https://github.com/lichen-lab/DeepPerVar
Highly selective transgene expression through double-floxed inverted orientation system by using a unilateral spacer sequence
Authors: Matsushita Natsuki , Kato Shigeki , Nishizawa Kayo , Sugawara Masateru , Takeuchi Kosei , Miyasaka Yoshiki , Mashimo Tomoji , Kobayashi Kazuto
Published: April 2022

The double-floxed inverted orientation (DIO) system with adeno-associated viral (AAV) vector provides a beneficial approach to express transgenes in specific cell populations having Cre recombinase. A significant issue with this system is the protection against non-specific expression of transgenes in tissues after vector injection. We here show that Cre-independent recombination in AAV genome carrying the DIO sequence occurs during the production of viral vectors in packaging cells, which results in transgene expression in off-target populations. Introduction of a relatively longer nucleotide sequence between two recognition sites at the unilateral side of the transgene cassette, termed a unilateral spacer sequence (USS), is useful to suppress recombination during the vector production, leading to the protection of non-specific transgene expression with enhanced gene expression selectivity. Our DIO/USS system offers a powerful strategy for highly specific Cre-dependent transgene expression, aiming at various applications for structural and functional analyses of target cell populations.
High levels of cyclic diguanylate interfere with beneficial bacterial colonization
Authors: Isenberg Ruth Y. , Christensen David G. , Visick Karen L. , Mandel Mark J.
Published: April 2022

During colonization of the Hawaiian bobtail squid (Euprymna scolopes),Vibrio fischeribacteria undergo a lifestyle transition from a planktonic motile state in the environment to a biofilm state in host mucus. Cyclic diguanylate (c-di-GMP) is a cytoplasmic signaling molecule that is important for regulating motility-biofilm transitions in many bacterial species.V. fischeriencodes 50 proteins predicted to synthesize and/or degrade c-di-GMP, but a role for c-di-GMP regulation during host colonization has not been investigated. We examined strains exhibiting either low or high levels of c-di-GMP during squid colonization and found that while a low c-di-GMP strain had no colonization defect, a high c-di-GMP strain was severely impaired. Expression of a heterologous c-di-GMP phosphodiesterase restored colonization, demonstrating that the effect is due to high c-di-GMP levels. In the constitutive high c-di-GMP state, colonizingV. fischeriexhibited reduced motility, altered biofilm aggregate morphology, and a regulatory interaction where transcription of one polysaccharide locus is inhibited by the presence of the other polysaccharide. Our results highlight the importance of proper c-di-GMP regulation during beneficial animal colonization, illustrate multiple pathways regulated by c-di-GMP in the host, and uncover an interplay of multiple exopolysaccharide systems in host-associated aggregates.

IMPORTANCE

There is substantial interest in studying cyclic diguanylate (c-di-GMP) in pathogenic and environmental bacteria, which has led to an accepted paradigm in which high c-di-GMP levels promote biofilm formation and reduce motility. However, considerably less focus has been placed on understanding how this compound contributes to beneficial colonization. Using theVibrio fischeri-Hawaiian bobtail squid study system, we took advantage of recent genetic advances in the bacterium to modulate c-di-GMP levels and measure colonization and track c-di-GMP phenotypes in a symbiotic interaction. Studies in the animal host revealed a c-di-GMP-dependent genetic interaction between two distinct biofilm polysaccharides, Syp and cellulose, that was not evident in culture-based studies: elevated c-di-GMP altered the composition and abundance of thein vivobiofilm by decreasingsyptranscription due to increased cellulose synthesis. This study reveals important parallels between pathogenic and beneficial colonization and additionally identifies c-di-GMP-dependent regulation that occurs specifically in the squid host.
Target-agnostic drug prediction integrated with medical record analysis uncovers differential associations of statins with increased survival in COVID-19 patients
Authors: Sperry Megan M. , Oskotsky Tomiko , Marić Ivana , Kaushal Shruti , Takeda Takako , Horvath Viktor , Powers Rani K. , Rodas Melissa , Furlong Brooke , Soong Mercy , Prabhala Pranav , Goyal Girija , Carlson Kenneth E. , Wong Ronald J. , Kosti Idit , Le Brian L. , Logue James , Hammond Holly , Frieman Matthew , Stevenson David K. , Ingber Donald E. , Sirota Marina , Novak Richard
Published: April 2022

Importance

Drug repurposing requires distinguishing established drug class targets from novel molecule-specific mechanisms and rapidly derisking their therapeutic potential in a time-critical manner, particularly in a pandemic scenario. In response to the challenge to rapidly identify treatment options for COVID-19, several studies reported that statins, as a drug class, reduce mortality in these patients. However, it is unknown if different statins exhibit consistent function or may have varying therapeutic benefit.

Objectives

To test if different statins differ in their ability to exert protective effects based on molecular computational predictions and electronic medical record analysis.

Main Outcomes and Measures

A Bayesian network tool was used to predict drugs that shift the host transcriptomic response to SARS-CoV-2 infection towards a healthy state. Drugs were predicted using 14 RNA-sequencing datasets from 72 autopsy tissues and 465 COVID-19 patient samples or from cultured human cells and organoids infected with SARS-CoV-2, with a total of 2,436 drugs investigated. Top drug predictions included statins, which were then assessed using electronic medical records containing over 4,000 COVID-19 patients on statins to determine mortality risk in patients prescribed specific statins versus untreated matched controls. The same drugs were tested in Vero E6 cells infected with SARS-CoV-2 and human endothelial cells infected with a related OC43 coronavirus.

Results

Simvastatin was among the most highly predicted compounds (14/14 datasets) and five other statins, including atorvastatin, were predicted to be active in > 50% of analyses. Analysis of the clinical database revealed that reduced mortality risk was only observed in COVID-19 patients prescribed a subset of statins, including simvastatin and atorvastatin.In vitrotesting of SARS-CoV-2 infected cells revealed simvastatin to be a potent direct inhibitor whereas most other statins were less effective. Simvastatin also inhibited OC43 infection and reduced cytokine production in endothelial cells.

Conclusions and Relevance

Different statins may differ in their ability to sustain the lives of COVID-19 patients despite having a shared drug target and lipid-modifying mechanism of action. These findings highlight the value of target-agnostic drug prediction coupled with patient databases to identify and clinically evaluate non-obvious mechanisms and derisk and accelerate drug repurposing opportunities.
Astrocyte-mediated transduction of muscle fiber contractions synchronizes hippocampal neuronal network development
Authors: Lee Ki Yun , Rhodes Justin S. , Saif M. Taher A.
Published: April 2022

Exercise supports brain health in part through enhancing hippocampal function. The leading hypothesis is that muscles release factors when they contract (e.g., lactate, myokines, growth factors) that enter circulation and reach the brain where they enhance plasticity (e.g., increase neurogenesis and synaptogenesis). However, it remains unknown how the muscle signals are transduced by the hippocampal cells to modulate network activity and synaptic development. Thus, we established an in vitro model in which the media from contracting primary muscle cells (CM) is applied to developing primary hippocampal cell cultures on a microelectrode array. We found that the hippocampal neuronal network matures more rapidly (as indicated by synapse development and synchronous neuronal activity) when exposed to CM than regular media (RM). This was accompanied by a 1.4-fold and 4.4-fold increase in the proliferation of neurons and astrocytes, respectively. Further, experiments established that the astrocytes release factors that inhibit neuronal excitability and facilitate network development. Results provide new insight into how exercise may support hippocampal function through regulating astrocyte proliferation and subsequent taming of neuronal activity into an integrated network.

Highlights

Contracting muscle conditioned media enhances neuronal activity.

Contracting muscle conditioned media expedites neuronal maturation and accumulation of filamentous actin at presynaptic terminals.

Contracting muscle conditioned media induces significant neuron and astrocyte proliferation.

Astrocytes release factors that inhibit muscle media-induced neuronal activity.
Hit-and-run silencing of endogenous DUX4 by targeting DNA hypomethylation on D4Z4 repeats in facioscapulohumeral muscular dystrophy
Authors: Sasaki-Honda Mitsuru , Jonouchi Tatsuya , Arai Meni , He Junjie , Okita Kazusa , Sakurai Satoko , Yamamoto Takuya , Sakurai Hidetoshi
Published: April 2022

Facioscapulohumeral muscular dystrophy (FSHD), a progressive skeletal muscle disorder, is epigenetically characterized by DNA hypomethylation of the D4Z4 repeats in the 4q35 region, which enables aberrant DUX4 expression. Sustainable DUX4 suppression is thus a promising therapeutic strategy by which to prevent disease progression, but most of the supposed methods to achieve this depend on the expression of a mediator biochemical entity that would potentially narrow the quality of life of individuals with FSHD in the clinical context. In this study, we report that by applying hit-and-run silencing with dCas9-mediated epigenetic editing targeting DNA hypomethylation on D4Z4 repeats, we could achieve the suppression of endogenous DUX4 in our FSHD patient-derived iPSC model. Notably, DNA methylation was significantly upregulated in FSHD cells and suppression effects were observed for at least two weeks after intervention, which was not the case with transient treatments of typical dCas9-KRAB alone. Off-target analysis showed that despite the potential genome-wide risk for DNA methylation, the impact on the transcriptome was limited. We propose that hit-and-run silencing could be a promising option to prevent disease progression with minimum intervention for individuals with FSHD, motivating further study for clinical development.
Gestational Ethanol Exposure Induces Sex-specific Striatal Acetylcholine and Dopamine Deficits
Authors: Bariselli Sebastiano , Mateo Yolanda , Reuveni Noa , Lovinger David M
Published: April 2022

Fetal alcohol exposure has deleterious consequences on the cognitive abilities and motor skills of patients affected by Fetal Alcohol Spectrum Disorder (FASD) and in pre-clinical models of gestational ethanol exposure (GEE). Deficits in striatal cholinergic and dopamine function impair action learning and execution, yet the effects of GEE on striatal acetylcholine and dopamine release remain unexplored. Here, we report that ethanol (EtOH) exposure during the first ten postnatal days (GEEP0-P10), which mimics EtOH consumption during the last gestational trimester in humans, induces enduring sex-specific anatomical and motor learning deficits in female mice. These behavioral impairments were accompanied by increased evoked-dopamine levels in the dorsolateral striatum (DLS) of GEEP0-P10 female, but not male, mice. Further experiments revealed impaired striatal β2-containing nicotinic acetylcholine receptor (nAChRs)-modulation of electrically evoked dopamine release. Using a genetically encoded acetylcholine sensor (GACh3.0), we found a reduced decay of acetylcholine transients in DLS of GEEP0-P10 females in the presence of an acetylcholinesterase inhibitor galantamine. Finally, we showed that this effect is associated with decreased excitability of striatal cholinergic interneurons (CINs), pointing to activity-dependent defects in acetylcholine release. Altogether, these data shed a new light on striatal deficits that might underlie cognitive and motor learning symptoms of patients affected by FASD.
Deciphering the mRNA-lncRNA-miRNA interaction landscape in human pluripotency
Authors: Ghosh Arindam , Som Anup
Published: April 2022

Human embryonic stem cells offer a huge potential for the study of early human development and for application in biomedical sciences. Growing evidence has shown that besides the protein coding genes, the non-coding elements of the human genome play a crucial role in maintaining its property of self renewal and in cell fate determination. However, a clear understanding of this regulatory mechanism and the landscape of interactions between the coding and non-coding elements was still lacking. To fill in this void, we use transcriptomic data from RNA-seq and small RNA-seq experiments to reconstruct the core pluripotency circuitry involving mRNAs, lncRNAs and miRNAs. The overall interaction landscape revealed an alternate circuit for the maintenance of pluripotency devoid of the classic pluripotency transcription factors NANOG, SOX2 and POU5F1. We also identified networks specific to the naive and primed states of human pluripotency revealing a new set of transcriptomic markers that could not only be used to differentiate pluripotent state from non-pluripotent state but also to identify the intra-pluripotency state. The lncRNA DANT1 was found to be crucial in determination to the two pluripotency states as it formed a bridge between the naive and primed state specific pluripotency networks. Further, we also identified and computationally validated putative ceRNA mechanism involving DANT1, the miRNAs hsa-miR-30c-2-3p, hsa-miR-210-3p and hsa-let-7b-5p, and several key pluripotency related genes including PTPRZ1, SALL2, TOX3, ZNF695, and ZYG11A which warrants further experimental validation.

HIGHLIGHTS

Reconstructed the key MLMi circuitry underlying human pluripotency by combining RNA-Seq data and known interaction information.

Identified an alternate pluripotency circuit devoid of classic pluripotency transcription factors NANOG, SOX2 and POU5F1.

Predicted a new set of markers that can not only distinguish between pluripotent and non-pluripotent states but also identify the intra-pluripotency state.

Identified novel putative function of lncRNA DANT1 as ceRNA in formation of naive and primed state pluripotency.

DANT1 harbours binding sites for miRNAs hsa-miR-30c-2-3p, hsa-miR-210-3p and hsa-let-7b-5p.
Two stages of bandwidth scaling drives efficient neural coding of natural sounds
Authors: He Fengrong , Stevenson Ian H. , Escabi Monty A.
Published: April 2022

Theories of efficient coding propose that the auditory system is optimized for the statistical structure of natural sounds, yet the transformations underlying optimal acoustic representations are not well understood. Using a database of natural sounds including human speech and a physiologically-inspired auditory model, we explore the consequences of peripheral (cochlear) and mid-level (auditory midbrain) filter tuning transformations on the representation of natural sound spectra and modulation statistics. Whereas Fourier-based spectrographic decompositions with equal resolution filters can preserve spectral details, cochlear filters with bandwidth scaling, sacrifice spectral information while producing a more robust temporal representation. Cochlear bandwidth scaling produces a frequency-dependent gain that counteracts the tendency of natural sound power to decrease with frequency, resulting in a whitened output representation. Mid-level auditory filter scaling further enhance the representation of natural sounds by producing a whitened modulation power spectrum (MPS) with higher modulation entropy than both the cochlear outputs and the conventional Fourier MPS. These findings suggest that the tuning characteristics of the peripheral and mid-level auditory system together produce a whitened output representation in three dimensions (frequency, temporal and spectral modulation) that reduces redundancies and allows for a more efficient use of neural resources. This hierarchical multi-stage tuning strategy is thus likely optimized to extract available information and may underlies perceptual sensitivity to natural sounds.
Effectiveness of COVID-19 vaccines against hospitalization and death in Canada: A multiprovincial test-negative design study
Authors: Nasreen Sharifa , Febriani Yossi , Velásquez García Héctor Alexander , Zhang Geng , Tadrous Mina , Buchan Sarah A. , Righolt Christiaan H. , Mahmud Salaheddin M. , Janjua Naveed Zafar , Krajden Mel , De Serres Gaston , Kwong Jeffrey C.
Published: April 2022

Background

A major goal of COVID-19 vaccination is to prevent severe outcomes (hospitalizations and deaths). We estimated the effectiveness of mRNA and ChAdOx1 COVID-19 vaccines against severe outcomes in four Canadian provinces between December 2020 and September 2021.

Methods

We conducted this multiprovincial retrospective test-negative study among community-dwelling adults aged ≥18 years in Ontario, Quebec, British Columbia, and Manitoba using linked provincial databases and a common study protocol. Multivariable logistic regression was used to estimate province-specific vaccine effectiveness against COVID-19 hospitalization and/or death. Estimates were pooled using random effects models.

Results

We included 2,508,296 tested subjects, with 31,776 COVID-19 hospitalizations and 5,842 deaths. Vaccine effectiveness was 83% after a first dose, and 98% after a second dose, against both hospitalization and death (separately). Against severe outcomes (hospitalization or death), effectiveness was 87% (95%CI: 71%–94%) ≥84 days after a first dose of mRNA vaccine, increasing to 98% (95%CI: 96%–99%) ≥112 days after a second dose. Vaccine effectiveness against severe outcomes for ChAdOx1 was 88% (95%CI: 75%–94%) ≥56 days after a first dose, increasing to 97% (95%CI: 91%–99%) ≥56 days after a second dose. Lower one-dose effectiveness was observed for adults aged ≥80 years and those with comorbidities, but effectiveness became comparable after a second dose. Two doses of vaccines provided very high protection for both homologous and heterologous schedules, and against Alpha, Gamma, and Delta variants.

Conclusions

Two doses of mRNA or ChAdOx1 vaccines provide excellent protection against severe outcomes of hospitalization and death.
Mechanical aspects of mothership with sensing drones system
Authors: Pakuła Aleksandra , Muchla Grzegorz , Załęcki Bartosz , Modzelewski Michał Jakub , Goetzendorf-Grabowski Tomasz
Published: April 2022

Purpose

This paper aims to describe the mechanical aspects of unmanned Mothership Plane and Sensing Drones. The presented conceptual system shows the idea and possible way of designing different sizes and objective systems based on experience gained during the SAE Aero Design Competition.

Design/methodology/approach

The UAS is based on a SAE Aero Design Competition designed and manufactured Mothership Plane converted to a high endurance platform modified to launch up to six small copters. The process of designing and converting the Mothership is described. The methodology of selecting and planning either the structure or hardware of the drones is presented.

Findings

A key finding is that the presented conception of mothership plane deploying in flight a group of small sensing multirotors is achievable. Moreover, the modular build of the system provides the possibility to adapt currently existing unmanned aircrafts to be converted to the described mothership plane.

Practical implications

To conduct flight tests and to study encountered problems. Presentation of the unmanned aerial system (UAS) concept that can be used to scan an area and create 3D maps for Search and Rescue missions as well as agriculture applications.

Originality/value

The paper describes the conceptual approach to design a UAS consisting of the mothership plane and the sensing drones. The paper highlights the potential solutions gained by using such a UAS. The focus is to present a technology and system that can perform real time observations in widespread and difficult to reach areas.
Triple-speed coaxial magnetic gear for wind turbine applications: introduction and comprehensive analysis
Authors: Moghimi Ali , Hosseini Aliabadi Mahmood , Feshki Farahani Hassan
Published: April 2022

Purpose

This paper aims to introduce a new structure for coaxial magnetic gears.

Design/methodology/approach

The study discusses the design and electromagnetic modeling of a triple-speed coaxial magnetic gear (TSCMG) for three different levels of torques in special applications such as wind energy conversion and electrical vehicles. The proposed TSCMG consists of inner, middle and outer rotor, which has one rotor more than its conventional counterpart. The suggested TSCMG’s related equations such as transform ratio and torque are calculated, then TSCMG is simulated in a finite element environment. A comprehensive study has been done on TSCMG, and results are compared with two other magnetic gears with the same volume but two speeds.

Findings

The obtained results show that the proposed structure for TSCMGs is significantly practical and applicable in higher ranges of torques. Finally, an experimental TSCMG is prototyped to verify the results.

Originality/value

The achievements are excellent and confirm that TSCMG can be used as powerful equipment in a wide range of application like permanent wind turbines to generate electricity in 24 h per every single day.
Inside the black box: How can gender diversity make a difference in the boardroom?
Authors: Khemakhem Hanen , Maalej Manel , Fontaine Richard
Published: April 2022

Purpose

Prior research shows that a board of directors' gender diversity positively influences organizations. However, little is known about how and why gender diversity influences the board of directors' functioning and decisions. The objective of this paper is to investigate the differences between women and men when fulfilling their role as directors.

Design/methodology/approach

This research uses a qualitative approach based on 29 in-depth semi-structured interviews with female and male board members.

Findings

The authors’ findings reveal that women are as involved as men in the board tasks and responsibilities. Also, women have the same understanding as men of their role and of the skills needed to be board members. However, women fulfil their role differently than men. Women come to board meetings more prepared, take more notes and do more follow-up, and they also dare to ask tough questions to top management. Women directors bring a different point of view — representing different interests — to board discussions, have a different communication style, are not a part of the boys' club and have a social upbringing that might explain gender differences in the boardroom.

Research limitations/implications

This study could help boards and policymakers introduce diversity measures and provide ways to better integrate women into top decision-making groups such as board of directors.

Practical implications

This study's findings can help organizations include females in key decision-making groups such as board of directors.

Social implications

This study reveals that in the same social setting, with the same role and expectations, and the same understanding of their role, both genders continue to perform differently.

Originality/value

Based on direct evidence from board members, this study highlights how and why women do their role in the boardroom differently.
Examining toxic supervision in higher education in India
Authors: Shahnawaz Mohammad Ghazi , Siddiqi Nasrina
Published: April 2022

Purpose

With issues like increasing student dropout rates, low productivity and compromised quality, research in higher education is faced with a number of paralyzing challenges in India. This study aims to locate the role of toxic academic supervision in relation to decreased quality of research.

Design/methodology/approach

Following a sequential mixed method design, the research begins with a quantitative analysis, which is then followed by an in-depth qualitative exploration.

Findings

The results of mediation analysis in this study reveal that students who experience toxic research supervision have a weak sense of identification and are also poor at self-disclosure, which results in increased distress and reduced engagement and productivity. Moreover, identification and self-disclosure have also been found to partially mediate the relationship between toxic supervision and distress. Furthermore, a thematic analysis of this study provides a detailed behavioral profile of toxic academic supervisors and highlights the consequences of such supervision with regard to students' well-being and productivity.

Research limitations/implications

In terms of theoretical contributions, the study provides evidence that the concept of toxic leadership has applicability outside of the organizational context; in the educational sphere as well and that the toxic leadership scale can be successfully used to assess the severity of toxic supervision within the academic domain, and corrective actions can be taken to mitigate the effect of such supervisory style on students.

Practical implications

The study not only highlights the repercussions of toxicity in academia and higher education but also provides a detailed and in-depth description of the personality traits and behavioral idiosyncrasies of toxic supervisors, which can help in the early identification of toxic tendencies and can enable us to mitigate and prevent toxicity from the academic space and to ensure a conducive environment for students in higher education. Overall, the present research has important implications for researchers, academicians as well as policymakers.

Originality/value

The study is the first of its kind in terms of both, objective and methodology.
Analysing the impact of sustainable human resource management practices and industry 4.0 technologies adoption on employability skills
Authors: Sharma Manu , Luthra Sunil , Joshi Sudhanshu , Kumar Anil
Published: April 2022

Purpose

The study aims to examine the influence of Sustainable Human Resource Management (SHRM) practices and Industry 4.0 Technologies (I4Te) adoption on the Employability Skills (ES) of the employees. The study has undertaken four major SHRM practices – Training (TR), Flexibility (FL), Employee Participation (EP) and Employee Empowerment (EE) to measure its impact on the ES along with I4Te.

Design/methodology/approach

A survey approach method was designed on the identified constructs from existing literature based on SHRM, I4Te and ES. The survey resulted into 198 valid responses. The study used confirmatory factor analysis (CFA) and structural equation modelling (SEM) using SPSS 25.0 and AMOS 25.0 for constructs validation and hypothesis testing.

Findings

The current study reveals that all the four SHRM practices (TR, FL, EP and EE) along with I4Te directly influence ES in the organisation. The I4Te along with the SHRM practices may bring enhancement in the skills and competencies of the employees that is the requirement of future organisations.

Practical implications

Considering the results, the SHRM practices aligned with I4Te may directly influence the employee's ES including core skills, IT skills and personal attributes. The SHRM practices in the organisation will enhance the opportunities for the employees and bring long-term association with the employees.

Social implications

For the development of the economy and the individual, the SHRM practices need to conduct themselves in more socially responsible ways along with the I4Te to enhance the ES of the employees. The individual development will bring sustainable behavioural changes in the employees.

Originality/value

There has been no research conducted on exploring SHRM, I4Te and ES together. This is the pioneer in the HRM fields that explores the interrelationships and influence amongst the five constructs undertaken in the study.
Corporate image as an enabler of customer retention
Authors: Leong Vai Shiem , Hj Ahady Diyana Maslina , Muhamad Nazlida
Published: April 2022

Purpose

This study aims to examine the extent of corporate image of mobile telecommunication company on service quality and price fairness, which subsequently play important roles in influencing customer satisfaction and loyalty.

Design/methodology/approach

A questionnaire was administered to subscribers of mobile service providers in Brunei. The proposed research model was tested using structural equation modeling to estimate the relationships between corporate image, service quality, price fairness, customer satisfaction and loyalty.

Findings

The results indicated that favorable corporate image positively affects network quality, customer support and price fairness, which, in turn, lead to formation of customer satisfaction and customer loyalty.

Originality/value

This study demonstrates the magnitude of corporate image as an enabler of market dominance, recognizing that superior corporate image can become a first mover advantage and competitive advantage, which explains the high customer retention of a mobile telecommunication company. The effects of corporate image as a first mover advantage have not been highlighted in the literature of first mover advantage of mobile telecommunication; therefore, this study provides a new insight in this study area.
Addressing homelessness with the “human ecology economics” framework: the role of the business community in California
Authors: Allen Roy Evan , Burns Caroline , Subrahmanyan Saroja
Published: April 2022

Purpose

The purpose of this paper is to provide a human ecology economics (HEE) framework for understanding and addressing homelessness, especially as it exists in California and the San Francisco Bay Area. The role of business and private “stakeholders of the homeless” is emphasized.

Design/methodology/approach

The HEE approach relies on evolutionary and complex systems processes, and it incorporates interdisciplinary material from the humanities. Within HEE, an early-stage exploratory research method is used. In-depth interviews with 16 long-term residents who are also managers in various organizations help to identify private-sector perceptions including how businesses can engage with and support the homeless.

Findings

In the current balance between needed supplies of “production capital,” which includes affordable housing, shelter beds, food, clothing, medical supplies and so on and “transaction capital,” which is an interacting mix of social capital, informational capital and financial capital, the authors find that the business community needs to pay greater attention to deficits in “transaction capital.”

Research limitations/implications

It is beyond the scope of this paper, and beyond the current ability of complex system modeling, to prioritize the best interventions across various types of homeless communities. However, for early-stage research, the authors have provided a useful ontology of the human ecology of homelessness that might inform further research and policy initiatives. Follow-on research might then investigate, with more rigorous methods, the narrower causalities between subcomponents of one’s ontology.

Originality/value

Scholars, policymakers and business community activists might appreciate the more comprehensive and accessible interdisciplinary framework for understanding the causes and possible responses to homelessness.