bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of direct-acting antivirals in maintenance hemodialysis patients complicated with chronic hepatitis C
Authors: Li Chunhong , Liang Jing , Xiang Huiling , Chen Haiyan , Tian Jie
Published: November 2020

Hepatitis C virus (HCV) infection is very common in maintenance hemodialysis patients, causing high morbidity and mortality. This study aimed to evaluate the effectiveness and adverse events of direct-acting antivirals (DAAs) in maintenance hemodialysis patients complicated with chronic hepatitis C in real-world clinical practice.

In this retrospective observational study, hemodialysis patients with chronic hepatitis C infection in the Third Central Hospital of Tianjin outpatient were screened, and appropriate treatment plans were selected accordingly. Totally 25 patients diagnosed with chronic hepatitis C and treated with DAAs for 12 weeks or 24 weeks were included. The sustained virologic response (SVR) rate obtained 12 weeks post-treatment (SVR12) was evaluated. Laboratory indexes and adverse reactions during the treatment process were also assessed.

A total of 25 cases met the eligibility criteria and provided informed consent. Except for 1 patient who discontinued the treatment due to gastrointestinal bleeding, the remaining 24 cases completed the treatment cycle with 100% rapid virologic response (RVR) and 100% SVR12, with no serious adverse reactions recorded.

Maintenance hemodialysis patients complicated with chronic hepatitis C in Chinese real-world setting tolerate DAAs very well, with a viral response rate reaching 100%.
Differential expression of transfer RNA-derived small RNAs in IgA nephropathy
Authors: Luo Zhi-Feng , Tang Donge , Xu Hui-Xuan , Lai Liu-Sheng , Chen Jie-Jing , Lin Hua , Yan Qiang , Zhang Xin-Zhou , Wang Gang , Dai Yong , Sui Wei-Guo
Published: November 2020

Background:

IgA nephropathy (IgAN) is one of the most common forms of primary glomerulonephritis. Recent studies have indicated that small noncoding RNAs, such as tRNA-derived small RNAs (tsRNAs), might be novel biomarkers for glomerulonephritis. We therefore investigated the potential roles and possible functions of the tsRNAs in IgAN.

Method:

Peripheral blood mononuclear cells (PBMCs) were extracted from blood samples of the patients with IgAN and healthy control groups. The expression profiles of tsRNAs were assessed by small RNA sequencing (RNA-Seq) in PBMCs of the IgAN and control groups. Dysregulated tsRNAs were selected for validation by quantitative real-time polymerase chain reaction (qRT-PCR). Target gene prediction and enrichment were performed by bioinformatics analysis.

Results:

The results revealed that 143 significantly upregulated and 202 significantly downregulated tsRNAs were differentially altered in the IgAN group compared with the control group. Five upregulated tsRNAs (tRF-Val-AAC-007, tRF-Ala-AGC-063, tRF-Gln-CTG-010, tRF-Tyr-GTA-011 and tRF-Thr-AGT-007) and 3 downregulated tsRNAs (tiRNA-Val-TAC-004, tRF-Gly-CCC-005 and tRF-His-GTG-006) were selected for validation by qRT-PCR; the results were consistent with the sequencing data. Gene Ontology (GO) analysis revealed that the target genes predicted by upregulated tsRNAs were mostly enriched in “nucleic acid metabolic process," “intracellular part," and “ion binding," whereas the target genes predicted by downregulated tsRNAs were mostly enriched in “regulation of cellular component organization," “membrane-bound organelle," and “ion binding." Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes predicted by upregulated tsRNAs were mostly enriched in “herpes simplex virus 1 infection," whereas the target genes predicted by downregulated tsRNAs were mostly enriched in “circadian rhythm

Conclusions:

The present study confirmed the differential expression of tsRNAs in patients with IgAN, and these dysregulated tsRNAs might be novel potential targets for the diagnosis and treatment of IgAN.
The limits of cosmology: role of the Moon
Authors: Silk Joseph
Published: November 2020

The lunar surface allows a unique way forward in cosmology, to go beyond current limits. The far side provides an unexcelled radio-quiet environment for probing the dark ages via 21 cm interferometry to seek elusive clues on the nature of the infinitesimal fluctuations that seeded galaxy formation. Far-infrared telescopes in cold and dark lunar polar craters will probe back to the first months of the Big Bang and study associated spectral distortions in the CMB. Optical and IR megatelescopes will image the first star clusters in the Universe and seek biosignatures in the atmospheres of unprecedented numbers of nearby habitable zone exoplanets. The goals are compelling and a stable lunar platform will enable construction of telescopes that can access trillions of modes in the sky, providing the key to exploration of our cosmic origins.

This article is part of a discussion meeting issue ‘Astronomy from the Moon: the next decades (part 1)’.
A 20 m wide-field diffraction-limited telescope
Authors: Eads Ryker W. , Angel J. Roger P.
Published: November 2020

A 20 m space telescope is described with an unvignetted 1° field of view—a hundred times larger in area than fields of existing space telescopes. Its diffraction-limited images are a hundred times sharper than from wide-field ground-based telescopes and extend over much if not all the field, 40 arcmin diameter at 500 nm wavelength, for example. The optical system yielding a 1°, 1.36 m diameter image at f/3.9 has relatively small central obscuration, 9% by area on axis, and is fully baffled. Several carousel-mounted instruments can each access directly the full image. The initial instrument complement includes a 400 gigapixel silicon imager with 2 µm pixels (0.005 arcsec), and a 60 gigapixel HgCdTe imager with 5 µm pixels (0.012 arcsec). A multi-object spectrograph with 10 000 fibres will allow spectroscopy with 0.02 arcsec resolution. Direct imaging and spectroscopy of exoplanets can take advantage of the un-aberrated, on-axis image (5 nm RMS wavefront error). While this telescope could be built for operation in free space, a site accessible to a human outpost at the Moon's south pole would be advantageous, for assembly and repairs. The lunar site would allow also for the installation of new instruments to keep up with evolving scientific priorities and advancing technology. Cooling to less than 100E K would be achieved with a surrounding cylindrical thermal shield.

This article is part of a discussion meeting issue ‘Astronomy from the Moon: the next decades (part 1)’.
Concurrent anatomical, physiological and network changes in cognitively impaired multiple sclerosis patients
Authors: Jandric Danka , Lipp Ilona , Paling David , Rog David , Castellazzi Gloria , Haroon Hamied , Parkes Laura , Parker Geoff , Tomassini Valentina , Muhlert Nils
Published: November 2020

Cognitive impairment in multiple sclerosis is associated with functional connectivity abnormalities, but the pathological substrates of these abnormalities are not well understood. It has been proposed that resting-state network nodes that integrate information from disparate regions are susceptible to metabolic stress, which may impact functional connectivity. In multiple sclerosis, pathology could increase metabolic stress within axons, damaging the anatomical connections of network regions, and leading to functional connectivity changes. We tested this hypothesis by assessing whether resting state network regions that show functional connectivity abnormalities in people with cognitive impairment also show anatomical connectivity abnormalities.

Multimodal MRI and neuropsychological assessments were performed in 102 relapsing remitting multiple sclerosis patients and 27 healthy controls. Patients were considered cognitively impaired if they obtained a z-score of ≤1.5 on ≥2 tests of the Brief Repeatable Battery of Neuropsychological Tests (n=55). Functional connectivity was assessed with Independent Component Analysis of resting state fMRI images, and anatomical connectivity with Anatomical Connectivity Mapping of diffusion-weighted MRI. Exploratory analyses of fractional anisotropy and cerebral blood flow changes were conducted to assess local tissue characteristics.

We found significantly decreased functional connectivity in the anterior and posterior default mode networks and significant increases in the right and left frontoparietal networks in cognitively impaired relative to cognitively preserved patients. Networks showing functional abnormalities also showed reduced anatomical connectivity and white matter microstructure integrity as well as reduced local tissue cerebral blood flow.

Our results identify key pathological correlates of functional connectivity abnormalities associated with impaired cognitive function in multiple sclerosis, consistent with metabolic dysfunction in functional network regions.
Comparative analysis of the first wave of the COVID-19 pandemic in South Korea, Italy, Spain, France, Germany, the United Kingdom, the USA and the New-York state
Authors: Alvarez Luis
Published: November 2020

We use an exponential growth model to analyze the first wave of the COVID-19 pandemic in South Korea, Italy, Spain, France, Germany, the United Kingdom, the USA and the New-York state. This model uses the number of officially reported patients tested positive and deaths to estimate an infected hindcast of the cumulative number of patients who later tested positive or who later die. For each region, an epidemic timeline is established, obtaining a precise knowledge of the chronology of the main epidemiological events during the full course of the first wave. It includes, in particular, the time that the virus has been in free circulation before the impact of the social distancing measures were observable. The results of the study suggest that among the analyzed regions, only South Korea and Germany possessed, at the beginning of the epidemic, a testing capacity that allowed to correctly follow the evolution of the epidemic. Anticipation in taking measures in these two countries caused the virus to spend less time in free circulation than in the rest of the regions. The analysis of the growth rates in the different regions suggests that the exponential growth rate of the cumulative number of infected, when the virus is in free circulation, is around 0.250737. In addition, we also study the ability of the model to properly forecast the epidemic spread at the beginning of the epidemic outbreak when very little data and information about the coronavirus were available. In the case of France, we obtain a reasonable estimate of the peak of the new cases of patients tested positive 9 days in advance and only 7 days after the implementation of a strict lockdown.
Psychosocial Health of School-aged Children during the Initial COVID-19 Safer-at-Home School mandates in Florida: A cross-sectional study
Authors: McKune Sarah , Acosta Daniel , Diaz Nick , Brittain Kaitlin , Joyce-Beaulieu Diana , Maurelli Anthony T. , Nelson Eric J.
Published: November 2020

Background

Given the emerging literature regarding the impacts of lockdown measures on mental health, this study aims to identify risk factors in school-aged children for being at risk for psychosocial disorders during the COVID-19 Safer-at-Home School mandates in Florida

Methods

A cross-sectional study was conducted in April 2020 (n=280). Bivariate analysis and logistic and multinomial logistic regression models are used to examine socio-demographic and knowledge, attitude, and practice (KAP) predictors of anxiety, depression, and obsessive- compulsive disorder (OCD).

Results

Loss of household income was associated with being at risk for depression [aOR=3.130, 95% CI= (1.41-6.97)], anxiety [aOR=2.531, 95%CI= (1.154-5.551)], and OCD [aOR=2.90, 95%CI= (1.32-6.36)]. Being female was associated with risk for depression [aOR=1.72, 95% CI=(1.02-2.93)], anxiety [aOR=1.75, 95% CI=(1.04-2.97)], and OCD[aOR=1.764, 95%CI= (1.027-3.028)]. Parental practices that are protective against COVID-19 were associated with children being at risk of depression [aOR=1.55, 95% CI= (1.04-2.31)]. Being at a lower school level was risk factor for anxiety and OCD.

Conclusions

Efforts to address mental health risk in children, as a result schools should prioritize girls, younger children, and children of families who lose income. Limiting the spread of COVID-19 through school closure may exacerbate the risk of psychosocial disorders in children, thus school administrators should move quickly to target those at greatest risk.
My voice therefore I spoke: sense of agency over speech enhanced in hearing self-voice
Authors: Ohata Ryu , Asai Tomohisa , Imaizumi Shu , Imamizu Hiroshi
Published: November 2020

The subjective experience of causing an action is known as the sense of agency. Dysfunction in the sense of agency has been suggested as a cause of auditory hallucinations (AHs), an important diagnostic criterion for schizophrenia. However, agency over speech has not been extensively characterized in previous empirical studies. Here, we examine both implicit and explicit measures of the sense of agency and reveal bottom-up and top-down components that constitute self-agency during speech. The first is action-outcome causality, which is perceived based on a low-level sensorimotor process when hearing their own voice following their speech. The second component is self-voice identity, which is embedded in the acoustic quality of voice and dominantly influences agency over speech at the cognitive judgment level. Our findings provide profound insight into the sense of agency over speech and present an informative perspective for understanding aberrant experience in AHs.
BCG vaccine derived peptides induce SARS-CoV-2 T cell cross-reactivity
Authors: Eggenhuizen Peter J. , Ng Boaz H. , Chang Janet , Fell Ashleigh L. , Wong Wey Y. , Gan Poh- Yi , Holdsworth Stephen R. , Ooi Joshua D.
Published: November 2020

Epidemiological studies suggest that the Bacillus Calmette-Guérin (BCG) vaccine may have protective effects against coronavirus disease 2019 (COVID-19); and, there are now more than 15 ongoing clinical trials seeking to determine if BCG vaccination can prevent or reduce the severity of COVID-19 (1). However, the mechanism by which BCG vaccination can induce a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific T cell response is unknown. Here, in silico, we identify 8 BCG derived peptides with significant sequence homology to either SARS-CoV-2 NSP3 or NSP13 derived peptides. Using an in vitro co-culture system, we show that human CD4+ and CD8+ T cells primed with a BCG derived peptide developed enhanced reactivity to its corresponding SARS-CoV-2 derived peptide. As expected, HLA differences between individuals meant that not all persons developed immunogenic responses to all 8 BCG derived peptides. Nevertheless, all of the 20 individuals that were primed with BCG derived peptides developed enhanced T cell reactivity to at least 7 of 8 SARS-CoV-2 derived peptides. These findings provide a mechanistic basis for the epidemiologic observation that BCG vaccination confers protection from COVID-19; and supports the use of BCG vaccination to induce cross-reactive SARS-CoV-2 specific T cell responses.
Role of asymptomatic COVID-19 cases in viral transmission: Findings from a hierarchical community contact network model1
Authors: Luo Tianyi , Cao Zhidong , Wang Yuejiao , Zeng Daniel Dajun , Zhang Qingpeng
Published: November 2020

Background

As part of on-going efforts to contain the COVID-19 pandemic, understanding the role of asymptomatic patients in the transmission system is essential to infection control. However, optimal approach to risk assessment and management of asymptomatic cases remains unclear.

Methods

This study involved a SEINRHD epidemic propagation model, constructed based on epidemiological characteristics of COVID-19 in China, accounting for the heterogeneity of social network. We assessed epidemic control measures for asymptomatic cases on three dimensions. Impact of asymptomatic cases on epidemic propagation was examined based on the effective reproduction number, abnormally high transmission events, and type and structure of transmission.

Results

Management of asymptomatic cases can help flatten the infection curve. Tracking 75% of asymptomatic cases corresponds to an overall reduction in new cases by 34.3% (compared to tracking no asymptomatic cases). Regardless of population-wide measures, family transmission is higher than other types of transmission, accounting for an estimated 50% of all cases.

Conclusions

Asymptomatic case tracking has significant effect on epidemic progression. When timely and strong measures are taken for symptomatic cases, the overall epidemic is not sensitive to the implementation time of the measures for asymptomatic cases.
Constructing spatial perception through self-touch
Authors: Cataldo A. , Dupin L. , Dempsey-Jones H. , Gomi H. , Haggard P.
Published: November 2020

Classical accounts of spatial perception are based either on the topological layout of sensory receptors, or on implicit spatial information provided by motor commands. In everyday self-touch, as when stroking the left arm with the right hand, these elements are inextricably linked, meaning that tactile and motor contributions to spatial perception cannot readily be disentangled. Here, we developed a robot-mediated form of self-touch in order to decouple the spatial extent of active or passive movements from their tactile consequences. Participants judged the spatial extent of either the movement of the right hand, or of the resulting tactile stimulation to their left forearm. Across five experiments, we found bidirectional interference between motor and tactile information. Crucially, both directions of interference were stronger during active than passive movements. Thus, voluntary motor commands produced stronger integration of multiple signals relevant to spatial perception.
RepairSig: Deconvolution of DNA damage and repair contributions to the mutational landscape of cancer
Authors: Wojtowicz Damian , Hoinka Jan , Amgalan Bayarbaatar , Kim Yoo-Ah , Przytycka Teresa M.
Published: November 2020

Many mutagenic processes leave characteristic imprints on cancer genomes known as mutational signatures. These signatures have been of recent interest regarding their applicability in studying processes shaping the mutational landscape of cancer. In particular, pinpointing the presence of altered DNA repair pathways can have important therapeutic implications. However, mutational signatures of DNA repair deficiencies are often hard to infer. This challenge emerges as a result of deficient DNA repair processes acting by modifying the outcome of other mutagens. Thus, they exhibit non-additive effects that are not depicted by the current paradigm for modeling mutational processes as independent signatures. To close this gap, we present RepairSig, a method that accounts for interactions between DNA damage and repair and is able to uncover unbiased signatures of deficient DNA repair processes. In particular, RepairSigwas able to replace three MMR deficiency signatures previously proposed to be active in breast cancer, with just one signature strikingly similar to the experimentally derived signature. As the first method to model interactions between mutagenic processes, RepairSigis an important step towards biologically more realistic modeling of mutational processes in cancer. The source code for RepairSigis publicly available athttps://github.com/ncbi/RepairSig.
Dynamics ofORF1abandNGene among hospitalized COVID-19 positive cohorts: A hospital based retrospective study
Authors: Loying Pojul , Sarma Vaishali , Hazarika Suranjana C. , Kataki Monjuri , Raja Dina , Medhi Divyashree , Dutta Ridip , Chena Achu , Daimary Divya , Choudhury Aakangkhita , Saikia Lahari
Published: November 2020

1.

Objective

The present study hospital based retrospective study aimed at investigating the dynamics of ORF1ab and N gene from hospitalized COVID-19 positive cohorts considering the Ct values of both genes.

Study design and Methodology

Retrospective analyses of Ct values were done from 115 hospitalized COVID-19 positive patients in different time interval. Patients were admitted to the hospital either by RAT or/and RT-PCR and first RT-PCR testing were made after 9 days of incubation followed by testing in every 3 days of interval till negative, subsequently release of the patients.

Results

We have looked into the dynamics of ORF1ab and N gene and found that N gene require longer duration of days with 12.68 (S.D.±3.24) to become negative than ORF1ab with 12.09 (S.D.±2.88) days and it differs significantly (p=0.012; p<0.05). The persistent of N gene found in 46 patients out of 115 (39.65%) to the succeeding reading after 3 days. We have also looked into the mean differences in the between N and ORF1ab genes every readings separately and found that there were no significant differences between the mean Ct value of ORF1ab and N gene except in the day 3 (p=0.015; p<0.05). Further, we have looked into the relationship of age and gender of patients with the duration of positivity; however we did not find any significant role.

Conclusion

In COVID-19 hospital positive cohorts, the persistent of positivity of N gene is significantly for more duration than ORF1ab. As the SARS-CoV-2 is a new virus and study on it is evolving, so, exhaustive study is required on the dynamic of N gene positivity persistent in relation to the other pathophysiological parameters for the management and control of COVID-19.
Offering an Internet Survey Response Mode in a Flint Water Crisis Medicaid Population
Authors: Ford Sabrina , Oberst Kathleen , Ilardo Joan , An Hong Su , Jones Nicole , Hong Hyokyoung , Clark Karen , Luo Zhehui
Published: November 2020

Objective

To examine the preferred response mode (internet, phone, paper)to a Medicaid enrollee survey.

Data Source

Data was obtained from survey responses for a sub-sample of Flint Water Crisis Medicaid Expansion Waiver enrollees (N=2584).

Study Design

Enrollees were offered the choice of utilizing the internet, telephone, or mail to respond to a survey evaluating health services. Analyses were stratified by age, residency, race, and income. Chi-square was utilized to detect categorical differences.

Principal Findings

The majority (p<0.01) of participants responded by internet (55.46%), followed by mail (39.36%), and telephone (5.19%). Of those responding by internet, 75% used smart phones for connectivity. Weighted participation estimates for available survey modes showed variation by age, residence, race/ethnicity and poverty status. A smaller proportion (p<0.01) of ethnicities classified as Hispanic and Other used telephone participation compared to White or Black respondents.

Respondents at 200% Federal Poverty Level (FPL) or higher used internet at greater rates than those below 200% FPL (p<0.01).

Conclusions

Overall, this low-income population preferred the web-based response mode compared to paper or telephone, the variation by race and FPL suggests the continued presence of a digital divide in the population. Nevertheless, our findings revealed greater utilization of web-based tools for survey administration in vulnerable populations than was expected. This is a valuable finding that may inform future health programming and telehealth efforts particularly in the advent of COVID-19.

What this study adds

Active health care participation using internet connectivity is increasing and may be associated with improved quality and costs of health care services yet access and usage vary among populations.

Research suggests that persons of low income and resources are unable to participate with internet based activities due to access and literacy issues that may further exacerbate health disparities.

This study revealed enrollees of the Flint Michigan Section 1115 Demonstration utilized the internet for survey participation at a greater rate than responding by mail or phone.

Finding that vulnerable populations have greater access to the internet via digital technology than assumed may expand opportunities to participate in their health care through health information portals and telehealth.
Targeting mitochondrial respiration and the BCL2 family in MYC-associated B-cell lymphoma
Authors: Donati Giulio , Ravà Micol , Filipuzzi Marco , Nicoli Paola , Cassina Laura , Verrecchia Alessandro , Doni Mirko , Rodighiero Simona , Parodi Federica , Boletta Alessandra , Vellano Christopher P. , Marszalek Joseph R. , Draetta Giulio F. , Amati Bruno
Published: November 2020

Multiple molecular features, such as activation of specific oncogenes (e. g.MYC,BCL2) or a variety of gene expression signatures, have been associated with disease course in diffuse large B-cell lymphoma (DLBCL). Understanding the relationships between these features and their possible exploitation toward disease classification and therapy remains a major priority in the field. Here, we report that MYC activity in DLBCL is closely correlated with – and most likely a driver of – gene signatures related to Oxidative Phosphorylation (OxPhos). On this basis, we hypothesized that enzymes involved in Oxidative Phosphorylation, and in particular electron-transport chain (ETC) complexes, might constitute tractable therapeutic targets in MYC-associated lymphoma. Indeed, our data show that MYC sensitizes B-cells to IACS-010759, a selective inhibitor of ETC complex I. Mechanistically, IACS-010759 activates an ATF4-driven Integrated Stress Response (ISR), engaging the intrinsic apoptosis pathway through the transcription factor CHOP. In line with these findings, IACS-010759 shows synergy with the BCL2 inhibitor venetoclax against double-hit lymphoma (DHL), a high-grade form of DLBCL with concurrent activation ofMYCandBCL2. Similarly, in BCL2-negative lymphoma cell lines, inhibition of the BCL2-related protein Mcl-1 potentiates killing by IACS-010759. Altogether, ETC complex I inhibition engages the ISR to lower the apoptotic threshold in MYC-driven lymphomas and, in combination with select BCL2-family inhibitors, provides a novel therapeutic principle against this aggressive DLBCL subset.

Statement of significance

This work points to OxPhos as a key MYC-activated process and a tractable therapeutic target toward personalized treatment of high-grade DLBCL, providing strong context-dependent cooperation with BH3-mimetic compounds.
GEMC1-MCIDAS transcriptional program regulates multiciliogenesis in the choroid plexus and acts as a barrier to tumorigenesis
Authors: Li Qun , Han Zhiyuan , Singh Navleen , Terré Berta , Fame Ryann M. , Arif Uzayr , Page Thomas D. , Zahran Tasneem , Abdeltawab Ahmed , Huang Yuan , Cao Ping , Wang Jun , Lu Hao , Lidov Hart G.W. , Surendran Kameswaran , Wu Lizhao , Schüller Ulrich , Wechsler-Reya Robert J. , Lehtinen Maria K. , Roy Sudipto , Liu Zhongmin , Stracker Travis H. , Zhao Haotian
Published: November 2020

Multiciliated cells (MCCs) in the brain include the ependymal cells and choroid plexus (CP) epithelial cells. The CP secretes cerebrospinal fluid that circulates within the ventricular system, driven by ependymal cilia movement. However, the mechanisms and functional significance of multiciliogenesis in the CP remain unknown. Deregulated oncogenic signals cause CP carcinoma (CPC), a rare but aggressive pediatric brain cancer. Here we show that aberrant NOTCH and Sonic Hedgehog signaling in mice drive tumors that resemble CPC in humans. NOTCH-driven CP tumors were monociliated, whereas disruption of the NOTCH complex restored multiciliation and decreased tumor growth. NOTCH suppressed multiciliation in tumor cells by inhibiting the expression of GEMC1 and MCIDAS, early regulators of multiciliogenesis. Consistently, GEMC1-MCIDAS function is essential for multiciliation in the CP, and is critical for correcting multiciliation defect in tumor cells by a NOTCH inhibitor. Disturbances to theGEMC1program are commonly observed in human CPCs characterized by solitary cilia. Consistently, CPC driven by deletion ofTrp53andRb1in mice exhibits a cilia deficit consequent to loss ofGemc1-Mcidasexpression. Taken together, these findings reveal a GEMC1-MCIDAS multiciliation program in the CP critical for inhibiting tumorigenesis, and it may have therapeutic implications for the treatment of CPC.
A solution to temporal credit assignment using cell-type-specific modulatory signals
Authors: Liu Yuhan Helena , Smith Stephen , Mihalas Stefan , Shea-Brown Eric , Sümbül Uygar
Published: November 2020

Animals learn and form memories by jointly adjusting the efficacy of their synapses. How they efficiently solve the underlying temporal credit assignment problem remains elusive. Here, we re-analyze the mathematical basis of gradient descent learning in recurrent spiking neural networks (RSNNs) in light of the recent single-cell transcriptomic evidence for cell-type-specific local neuropeptide signaling in the cortex. Our normative theory posits an important role for the notion of neuronal cell types and local diffusive communication by enabling biologically plausible and efficient weight update. While obeying fundamental biological constraints, including separating excitatory vs inhibitory cell types and observing connection sparsity, we trained RSNNs for temporal credit assignment tasks spanning seconds and observed that the inclusion of local modulatory signaling improved learning efficiency. Our learning rule puts forth a novel form of interaction between modulatory signals and synaptic transmission. Moreover, it suggests a computationally efficient learning method for bio-inspired artificial intelligence.
Targeting aberrant dendritic integration to treat cognitive comorbidities of epilepsy
Authors: Masala Nicola , Pofahl Martin , Haubrich André N , Sameen Islam Khondker Ushna , Nikbakht Negar , Pasdarnavab Maryam , Kamali Fateme , Bohmbach Kirsten , Henneberger Christian , Golcuk Kurtulus , Ewell Laura A , Blaess Sandra , Kelly Tony , Beck Heinz
Published: November 2020

Memory deficits are a debilitating symptom of epilepsy, but little is known about mechanisms underlying cognitive deficits. Here, we describe a Na+channel-dependent mechanism underlying altered hippocampal dendritic integration, degraded place coding, and deficits in spatial memory.

Two-photon glutamate uncaging experiments revealed that the mechanisms constraining the generation of Na+spikes in hippocampal 1storder pyramidal cell dendrites are profoundly degraded in experimental epilepsy. A selective Nav1.3 sodium channel blocker reversed this effect, and Nav1.3 channels were up-regulated selectively in principal neurons at the mRNA level. Finally, in-vivo two-photon imaging revealed that the Nav1.3 channel blocker improves degraded hippocampal spatial representations, and reverses hippocampal memory deficits.

Thus, a dendritic channelopathy may underlie cognitive deficits in epilepsy and targeting it pharmacologically may constitute a new avenue to enhance cognition.

One Sentence Summary

Impaired input computations via aberrant dendritic spikes in chronic epilepsy degrade neuronal place codes and spatial memory
Milo:differential abundance testing on single-cell data using k-NN graphs
Authors: Dann Emma , Henderson Neil C. , Teichmann Sarah A. , Morgan Michael D. , Marioni John C.
Published: November 2020

Single-cell omic protocols applied to disease, development or mechanistic studies can reveal the emergence of aberrant cell states or changes in differentiation. These perturbations can manifest as a shift in the abundance of cells associated with a biological condition. Current computational workflows for comparative analyses typically use discrete clusters as input when testing for differential abundance between experimental conditions. However, clusters are not always an optimal representation of the biological manifold on which cells lie, especially in the context of continuous differentiation trajectories. To overcome these barriers to discovery, we presentMilo, a flexible and scalable statistical framework that performs differential abundance testing by assigning cells to partially overlapping neighbourhoods on a k-nearest neighbour graph. Our method samples and refines neighbourhoods across the graph and leverages the flexibility of generalized linear models, making it applicable to a wide range of experimental settings. Using simulations, we show thatMilois both robust and sensitive, and can reveal subtle but important cell state perturbations that are obscured by discretizing cells into clusters. We illustrate the power ofMiloby identifying the perturbed differentiation during ageing of a lineage-biased thymic epithelial precursor state and by uncovering extensive perturbation to multiple lineages in human cirrhotic liver.Milois provided as an open-source R software package with documentation and tutorials athttps://github.com/MarioniLab/miloR.
Do public governance and patriotism matter? Sales tax compliance among small and medium enterprises in developing countries: Jordanian evidence
Authors: Alshira'h Ahmad Farhan , Al-Shatnawi Hasan Mahmoud , Al-Okaily Manaf , Lutfi Abdalwali , Alshirah Malek Hamed
Published: November 2020

Purpose

The purpose of this study is to better understand the issues on tax compliance. This study aims to examine the influence of patriotism and public governance on the sales tax compliance of small and medium enterprises (SMEs) and to examine the interaction between patriotism and public governance on sales tax compliance.

Design/methodology/approach

This study was carried out by soliciting the opinions of owner-managers of SMEs in Jordan through a survey that was distributed by self-administered. This paper uses partial least squares structural equation modelling to investigate the influence of patriotism, public governance and the interaction of these two mechanisms on sales tax compliance for a sample of 385 SMEs.

Findings

This paper finds that patriotism and the public governance increase and improve the level of sales tax compliance. The findings also supported the interaction effect of patriotism on the relationship between public governance with sales tax compliance. Thus, all the hypothesised relationships were supported.

Practical implications

Tax authorities and policymakers in developing majority societies in developing countries and in other Arab countries, especially in Jordan, may use the results to focus their interest on the formulation of policies founded on the outcomes of the study to strengthen the compliance of eligible SMEs to further boost their sales collections.

Originality/value

Very few studies have examined the determinants of sales tax compliance, and there has been an absence of work that examines the influence of the patriotism and public governance on sales tax compliance. This paper, therefore, fills a gap in the literature by providing the first empirical evidence about the influence of patriotism and public governance on sales tax compliance of SMEs in developing countries. This study is the initial paper to examine the interaction between patriotism and public governance on sales tax compliance among SMEs in developing countries
The nexus of teaching, research and practice: perceptions and expectations of undergraduate education students in Southeast Turkey
Authors: Smirnova Yelena , Dos Bulent
Published: November 2020

Purpose

This study aims to explore the perceptions and expectations of the undergraduate students toward the teaching-research-practice nexus (TRPN) and propose a framework for the integration of nexus components at each undergraduate level. It also intends to identify whether students' views differ depending on their specialization, year of study, academic performance and gender.

Design/methodology/approach

Quantitative analysis was employed to evaluate the views of 460 undergraduate students from faculties of education in the Southeast Anatolia region of Turkey. The data were collected through the survey with a five-point Likert scale. A t-test and one-way ANOVA were used for the analysis of data.

Findings

Significant differences in the perceptions and expectations of the undergraduate students in relation to the TRPN suggest a gap in their satisfaction with the present teaching approach. The factors influencing students' perceptions include specialization, year of study and academic performance. Student expectations of the TRPN are affected by their specialization and GPA. The influence of gender was not confirmed.

Research limitations/implications

The lack of previous research on the TRPN creates a need for further development in this area of study. The sample limited to education faculty in one region precludes generalization of the findings beyond the study setting.

Practical implications

The present study provides preliminary information for education faculties on how to meet students' learning expectations through proportional integration of the TRPN components into the undergraduate curriculum.

Originality/value

The study contributes to the ongoing debate and scarce literature on the TRPN at the undergraduate level and proposes an original framework for linking teaching, research, and practice.
Determining nonfamily employees' job satisfaction and turnover intentions: the roles of job autonomy and work passion
Authors: Mustafa Michael , Ramos Hazel Melanie , Zainal Badri Siti Khadijah
Published: November 2020

Purpose

The purpose of this study seeks to examine how nonfamily employees' job autonomy and work passion can influence their job satisfaction and intention to quit in family small-to-medium-sized enterprises (SMEs). Current, research regarding the determinants of nonfamily employees' job satisfaction and turnover intentions has largely focused on the effects of family influence and family firm characteristics. Accordingly, not much is known of how the job characteristics and emotions of nonfamily employees influence their job satisfaction and intention to quit.

Design/methodology/approach

Data were collected from 160 nonfamily employees across 28 family-SMEs. Process macro was used to analyze the mediating role of nonfamily employees' work passion in the relationship between their job autonomy and job satisfaction and intention to quit.

Findings

Findings showed that nonfamily employees' job autonomy only had a significant direct effects on their job satisfaction and not their intention to quit. Subsequently, nonfamily employees' work passion was found to only partially mediate the relationship between their job autonomy and job satisfaction.

Originality/value

By focusing on the concepts of job autonomy and work passion, the study adds additional insights about the drivers of nonfamily employees' pro-organizational attitudes in family-SMEs. Also the study represents one of the first efforts in the literature to establish a link between job autonomy and the work passion of nonfamily employees with respect to their job satisfaction.
Drama pedagogy as a catalyst for shifting language anxiety in primary school teachers: offering critical engagement within EFL classroom
Authors: Araki Naoko
Published: November 2020

Purpose

Japanese school teachers are facing challenges under the new curricula reform, and there is still a lack of preparation to guide them to a successful implementation. Dilemmas related to teaching English language in primary schools were seen among participant teachers in a program of professional learning. This study aims (1) to identify a feeling of anxiety and readiness to the new EFL curricula and (2) to offer a professional learning program for shifting their concerns to regain their confidence and agency as educators.

Design/methodology/approach

The study was conducted based on qualitative research. Qualitative data was collected from 40 participating teachers in the professional learning program, and later was critically analysed.

Findings

Initial findings revealed that the majority of participants felt concerned towards teaching EFL in their school, as they are homeroom teachers, not specialist teachers in EFL. Drama pedagogy helped shifting their language anxiety and repositioning themselves within the new EFL curricular implementation, as it became evident through the reflections of the professional development workshop.

Originality/value

The study highlights current educational issues that Japanese primary school teachers are facing. Failure to fully address their feeling of anxiety underlies the Japanese school culture. Drama pedagogy, despite being quite new to educational pedagogy in Japan, was effective in allowing the participants to freely express their voices.
Discordance between patient‐reported and actual emergency department pain management
Authors: Taylor David McD , Valentine Safire , Majer James , Grant Nicole
Published: November 2020

Objective

To determine patient knowledge of the nature of their pain management in the ED.

Methods

This was a planned sub‐study of data collected during a randomised, controlled trial of the nature of the informed consent process in a single ED. Patients aged ≥18 years, with a triage pain score of ≥4, were enrolled. Forty‐eight hours post‐ED discharge, patients were asked if they had declined analgesia or if a range of pain management options had been administered. The primary outcome was discordance between the patient report and the ED report (proportion of cases where these reports differed).

Results

Outcome data were collected on 655 patients. There was significant discordance for all variables examined (P < 0.001). Discordance for patients declining analgesia was lowest at 8.9% (95% confidence interval [CI] 6.8–11.4). Discordance for administration of pain management ‘other’ than analgesia was highest at 32.6% (95% CI 29.0–36.4). Discordance for the administration of oral analgesia or ‘any’ analgesia was 17.1% (95% CI 14.3–20.3) and 14.4% (95% CI 11.8–17.3), respectively. For both of these outcomes, patients with chest pain and lower triage pain scores were more likely to report discordant responses. With the exception of ‘other’ pain management, smaller proportions of patients incorrectly reported not receiving management than incorrectly reporting that they did receive it.

Conclusion

Patients are often unaware of the nature of their pain management. They are most often unaware of management other than analgesia. Patients with chest pain and lower triage pain scores had the least knowledge of their pain management.
Diagnostic value of microRNAs for malignant pleural mesothelioma: A mini‐review
Authors: Han Yan‐Qiu , Xu Shang‐Cheng , Zheng Wen‐Qi , Hu Zhi‐De
Published: November 2020

Malignant pleural mesothelioma (MPM) is a type of cancer originating from the pleura with high aggressiveness and poor prognosis. A timely diagnosis is crucial to improve its prognosis. Laboratory biomarkers have significant advantages of reduced invasiveness, low cost, and are observer‐independent, and therefore represent a promising diagnostic tool for MPM. MicroRNA is a family of non‐coding RNA that regulates gene expression at the post‐transcriptional level. Accumulated studies showed that microRNA, either in tissue, circulating, and body fluid, has potential diagnostic value for various disorders. Here, we reviewed the diagnostic value of microRNA for MPM.
Social service as glasshouses? On the use and consequences of the Open Comparison system in Swedish social services
Authors: Johansson Staffan , Liljegren Andreas
Published: November 2020

Performance measurement (PM) systems where local governments performance is exposed to public scrutiny have been demanded in many OECD (Organisation for Economic Co‐operation and Development) countries. The experiences from the Swedish Open Comparisons (OC) system have been highlighted as a particularly interesting case because it bears similarities with both Anglo‐Saxon countries concerning coverage, scope, and transparency, and also with Continental European countries concerning voluntarism, sanctions, and policy sensitivity. The aim of this article is to investigate how managers and senior officials within the Swedish social services use the OC‐system, how they perceive its consequences, and also to understand how their use can be explained.

The study is based on concepts identified in previous research on use of performance information. The empirical investigation is based on a survey to 269 managers and senior officials in the social services in randomly selected municipalities.

The analysis shows that the OC system is mainly used for reporting to superior levels, identifying needs for improvements, and for evaluating the developments over time. The use is to a high extent determined by if the OC system has a strong support from the local leadership structure, and also if the users perceive it as a reliable and mature system. The users’ perceived consequences of the system concern changed attitudes, forms of governance, and also concrete operational processes.
Reluctant Generalised Additive Modelling
Authors: Tay J. Kenneth , Tibshirani Robert
Published: November 2020

Sparse generalised additive models (GAMs) are an extension of sparse generalised linear models that allow a model's prediction to vary non‐linearly with an input variable. This enables the data analyst build more accurate models, especially when the linearity assumption is known to be a poor approximation of reality. Motivated by reluctant interaction modelling, we propose a multi‐stage algorithm, called reluctant generalised additive modelling (RGAM), that can fit sparse GAMs at scale. It is guided by the principle that, if all else is equal, one should prefer a linear feature over a non‐linear feature. Unlike existing methods for sparse GAMs, RGAM can be extended easily to binary, count and survival data. We demonstrate the method's effectiveness on real and simulated examples.
From fitness landscapes evolution to automatic local search algorithm generation
Authors: Hénaux Vincent , Goëffon Adrien , Saubion Frédéric
Published: November 2020

Solving an optimization problem with local search algorithms consists of evolving a solution by means of an evaluation function, which is usually directly derived from the objective function of the problem. The resolution difficulties appear when the fitness landscape naturally induced by the problem instance is not perfectly exploitable, has a certain level of ruggedness, and therefore has many local optima. We propose here to shift the problem of searching a solution, from searching an evaluation function that maximizes the efficiency of the corresponding local search algorithm. In particular, we propose an evolution strategy scheme designed to evolve fitness functions and their corresponding fitness landscapes. The purpose is to generate a local search algorithm guided by an evolved fitness function specifically dedicated to tackling the problem instance to solve. Here, we focus on hill‐climbing algorithms and NK landscapes and show that such a strategy can be efficient to generate relevant search algorithms whose components are not problem‐specific.