bluuebunny/crossref_metadata_2025 huggingface dataset:
Asthma and severe acute respiratory syndrome coronavirus 2019: current evidence and knowledge gaps
Authors: Assaf Sara M. , Tarasevych Svitlana P. , Diamant Zuzana , Hanania Nicola A.
Published: October 2020

Purpose of review

Although respiratory viruses are common triggers of asthma exacerbation, it is unknown whether this also applies to infection with SARS-CoV-2. Indeed, patients with asthma and allergy appear underrepresented in large reports of COVID-19 cases worldwide. In this review, we evaluate existing literature on this topic and potential underlying mechanisms for any interrelationship between asthma and COVID-19.

Recent findings

Data from several preclinical and clinical reports suggest a lower susceptibility for COVID-19 in patients with underlying type 2 airway inflammation including asthma that may be related to a reduced expression of ACE2 and TMPRSS2 receptors for SARS-CoV-2. Corticosteroids further decrease expression of the ACE2 and TMPRSS2 receptors, hence may also have a protective effect against infection with SARS-CoV-2. In addition, some studies suggest that the reported improvement in asthma control and a reduction in asthma exacerbations during the COVID-19 pandemic may be related to improvement in adherence to controller therapy and reduced exposure to triggers, such as other respiratory viruses and air pollutants. Recent data point towards differential susceptibility for COVID-19 among asthma patients based on their phenotype and/or endotype. On the basis of existing evidence, continuation with controller therapies is recommended for all patients with asthma. For patients with severe uncontrolled asthma infected by SARS-CoV-2, adjustment of controllers and biologics should be based on a multidisciplinary decision.

Underrepresentation of SARS-CoV-2-infected patients with asthma and related allergic diseases may be based on potentially protective underlying mechanisms, such as type 2 airway inflammation, downregulation of ACE2/TMPRSS2 receptors, reduced exposures to triggers and improved adherence to controller medications. Although it is imperative that control should be maintained and asthma medications be continued in all patients, management of patients with severe uncontrolled asthma infected by SARS-CoV-2 including adjustment of controllers and biologics should be discussed on an individual basis.
An End-of-Life Care Educational Series to Improve Staff Knowledge and Comfort Levels
Authors: Rees June Nicole , Shields Erin , Altounji Diane , Murray Paula
Published: October 2020

Nursing staff play a key role in enhancing a patient's quality of life during end of life; however, they perceive lack of knowledge to be the largest barrier in providing quality end-of-life (EOL) care. Literature suggests that implementation of palliative and EOL care education can improve nursing EOL care practices. In order to address the gap in nursing knowledge and comfort, a quasi-experimental study was conducted; this study included the implementation of a multimodal EOL care educational series on an inpatient pediatric hematology oncology floor over 6 months. Prior to implementation, nursing staff completed a survey to measure perceived knowledge and comfort level regarding EOL care. The series included didactic sessions, in-services, case studies, practice exercises, and interactive discussions led by an interprofessional team of nurses, child-life specialists, and social workers. Educational topics included EOL symptom management, child-life services, supportive care resources, COMFORT communication, and an End-of-Life Nursing Education Consortium course. Following the educational series, the survey was repeated. Results of the survey demonstrated an increase in nursing knowledge and comfort levels. Significant improvements were observed across several items including medication management of dyspnea (χ
2
1,83 =5.1, P = .023), comfort with implementing interventions (χ
2
1,93 = 3.9, P = .049), and knowledge of hospital resources (χ
2
1,93 = 6.1, P = .014). These results suggest that while EOL education strategies can vary, a combination of learner engagement tactics can increase knowledge and comfort regarding EOL concepts and potentially positively impact nursing practice.
Incidental Finding of Endobronchial Metastasis by 18F-FDG PET/CT Leads to Change in Management in a Patient With Rectal Adenocarcinoma
Authors: Fabritius Matthias P. , Holzgreve Adrien , Knösel Thomas , Tiling Reinhold , Rübenthaler Johannes
Published: October 2020

A 58-year-old man with history of resected rectal adenocarcinoma and synchronous unifocal pulmonary metastasis showed a solitary pulmonary relapse in follow-up CT after 3 years of complete remission. Resection was planned. Preoperative 18F-FDG PET/CT detected a high focal 18F-FDG uptake in the left main bronchus. Bronchoscopy showed a papillary endobronchial lesion that was biopsied. Histology confirmed distant colorectal metastasis. The initial treatment plan changed, and the recommendation for systemic therapy was made by a multidisciplinary oncology team. Endobronchial metastases are rare and difficult to detect in conventional CT. PET/CT is useful to uncover endobronchial metastasis, which may change patient management.
18F-FDG PET/CT of Double Expressor High-Grade B-Cell Lymphoma in an Isolated Chest Wall Mass
Authors: Sharma Punit
Published: October 2020

18F-FDG PET/CT is now an integral part of management of high-grade B-cell lymphoma. It is used for staging, response evaluation, restaging, and surveillance. Although high-grade B-cell lymphoma most commonly presents with involvement of the lymph nodes, spleen, liver, and bone marrow, chest wall involvement is very rare. We present the staging 18F-FDG PET/CT findings in a case of an 82-year-old woman with double expressor high-grade B-cell lymphoma of isolated presternal anterior chest wall mass.
Recurrent Brain Metastasis of Triple Negative Breast Cancer With High Uptake in 68Ga-PSMA-11 PET/CT
Authors: Arslan Esra , Ergül Nurhan , Karagöz Yeşim , Gedik Arzu Algün , Çermik Tevfik Fikret
Published: October 2020

Triple negative breast cancer (TNBC) is characterized by poor prognosis and limited response to standard treatments. Although 18F-FDG PET/CT is frequently used in staging and restaging, in some cases, it may be insufficient considering tumor heterogeneity. Prostate-specific membrane antigen (PSMA) has been reported to be overexpressed in many types of cancer due to tumor-associated neovascularization. 68Ga-PSMA-11 PET/CT can be used to demonstrate radionuclide therapy option as well as detection of primary tumor and recurrence in TNBC. We present a 47-year-old woman with TNBC having recurrent brain metastasis with avid PSMA receptor activity versus low FDG uptake.
Sentinel Node Biopsy Alone or With Axillary Dissection in Breast Cancer Patients After Primary Chemotherapy: Long-Term Results of a Prospective Interventional Study
Authors: Martelli Gabriele , Barretta Francesco , Miceli Rosalba , Folli Secondo , Maugeri Ilaria , Listorti Chiara , Scaperrotta Gianfranco , Baili Paolo , Pruneri Giancarlo , Capri Giuseppe , Ferraris Cristina
Published: October 2020

Objective:

To ascertain, in cN0/1 breast cancer patients given primary chemotherapy followed by sentinel node biopsy (SNB), whether SNB alone is adequate axillary treatment if the sentinel nodes (SNs) are clear (pN0).

Summary Background Data:

2020 guidelines do not recommend SNB in most cN1 patients with clear SNs after primary chemotherapy because the high SNB false negative rate might lead to poorer outcomes.

Methods:

We prospectively assigned SNB after primary chemotherapy to 353 consecutive cT2 cN0/1 patients, median age 47 years (range 22-76) treated from 2007 to 2015. If the SNs were pN0, patients generally received no further axillary treatment (SNB only); if the SNs were pN1, completion axillary dissection (AD) (SNB + AD) was usually performed. Primary outcomes were overall (OS) and disease-free (DFS) survival in SNB only versus SNB + AD patients, assessed by Kaplan-Meier and compared using log-rank test, with use of propensity scores to account for bias due to nonrandom assignment to SNB versus SNB + AD.

Results:

Median follow-up was 108 months, interquartile range 66 to 136. OS and DFS did not differ significantly between the groups by propensity score- weighted comparison: 10-year OS 89% [95% confidence interval (CI): 81%- 99%] in SNB only patients versus 86% (95%CI: 78%–95%) in SNB + AD patients; 10-year DFS 79% (95%CI: 68%–92%) versus 69% (95%CI: 58%–81%). No SNB-only patient developed axillary failure.

Conclusions:

cT2 cN0/1 patients whose SNs are disease-free (pN0) after primary chemotherapy can be offered SNB (with no further axillary treatment if the SNs are negative), irrespective of axillary status beforehand, without affecting OS or DFS.
Ischemia-reperfusion Injury in Allogeneic Liver Transplantation: A Role of CD4 T Cells in Early Allograft Injury
Authors: Kageyama Shoichi , Kadono Kentaro , Hirao Hirofumi , Nakamura Kojiro , Ito Takahiro , Gjertson David W. , Sosa Rebecca A. , Reed Elaine F. , Kaldas Fady M. , Busuttil Ronald W. , Kupiec-Weglinski Jerzy W. , Zhai Yuan
Published: October 2020

Background.

A major discrepancy between clinical and most experimental settings of liver ischemia-reperfusion injury (IRI) is the allogenicity.

Methods.

In the current study, we first established a murine model of allogeneic orthotopic liver transplantation with extended cold ischemia time (18 h). Roles of CD4 T cells in the pathogenesis of IRI in liver allografts were determined using a depleting anti-CD4 antibody. The clinical relevance of CD4 as a marker of liver IRI was analyzed retrospectively in 55 liver transplant patients.

Results.

CD4 depletion in both donors and recipients resulted in the most effective protection of liver allografts from IRI, as measured by serum transaminase levels and liver histology. CD4 depletion inhibited IR-induced intragraft neutrophil/macrophage infiltration and proinflammatory gene expressions. Quantitative reverse-transcriptase polymerase chain reaction analysis of human liver biopsies (2 h postreperfusion) revealed that posttransplant, rather than pretransplant, CD4 transcript levels correlated positively with proinflammatory gene expression profile. When we divided patients into subgroups according to intragraft CD4 levels, the high CD4 cohort developed a more severe hepatocellular damage than that with low CD4 levels.

Conclusions.

CD4 T cells play a key pathogenic role in IRI of allogeneic liver transplants, and intragraft CD4 levels in the early postreperfusion phase may serve as a potential biomarker and therapeutic target to ameliorate liver IRI and improve orthotopic liver transplantation outcomes.
Adhaeribacter arboris sp. nov., and Adhaeribacter pallidiroseus sp. nov., novel bacteria isolated from birch tree (Betula platyphylla)
Authors: Kang Heeyoung , Kim Haneul , Cha Inseong , Joh Kiseong
Published: October 2020

Two Gram-stain-negative, strictly aerobic, non-motile and rod-shaped bacterial strains, designated as HMF7605T and HMF7616T, were isolated from birch tree, in Yong-in, Republic of Korea. Strains HMF7605T and HMF7616T exhibited the highest 16S rRNA gene sequence similarities of 95.9 and 97.5 % to

Adhaeribacter swui

17mud1-7T, 97.9 % between themselves. The values of average nucleotide identity and in silico DNA–DNA hybridization between strains HMF7605T and HMF7616T were 77.6 and 22.0 %, respectively. Phylogenetic analysis of the 16S rRNA gene sequences of the two strains revealed that they belonged to the genus

Adhaeribacter

within the family

Hymenobacteraceae

. The predominant fatty acids of both strains were iso-C15 : 0, summed feature 3 (comprising C16 : 1
 ω7c and/or C16 : 1
 ω6c), C16 : 1
 ω5c and summed feature 4 (comprising iso-C17 : 1 I and/or anteiso-C17 : 1 B). The both strains contained menaquinone-7 as the only isoprenoid quinone. The major polar lipid profiles of the two strains were similar with phosphatidylethanolamine, one unidentified aminophosphoglycolipid, one unidentified glycolipid and three unidentified polar lipids. The DNA G+C contents of strains HMF7605T and HMF7616T were 42.0 and 42.8 mol%, respectively. Based on the results of the phenotypic, genotypic, chemotaxonomic and phylogenetic investigation, two novel species, Adhaeribacter arboris sp. nov. and Adhaeribacter pallidiroseus sp. nov. are proposed. The type strains are HMF7605T (=KCTC 62465T=NBRC 113228T) and HMF7616T (=KCTC 62466T=NBRC 113229T), respectively.
Quantitative assessment on the severity degree of Alzheimer dementia by algebraic analysis on cortical thickness profiles of human brains
Authors: Kim Sangyeol , Park Seongjun , Chang Iksoo ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2020

Alzheimer disease(AD) affects profoundly the quality of human life. Quantifying the severity degree of Alzheimer dementia for an individual person is critical for the early diagnose and prescription for delaying the further dementia progression. However, the quantitative diagnose for human subjects of the mild cognitively impairment(MCI) or AD with the different degree of dementia severity is a difficult task due to both the very broad distribution of dementia severities and the lack of good quantitative determinant to assess it. Here, based on cortical thickness profiles of human brains measured by magnetic resonance experiment, a new algebraic approach is presented for the personalized quantification of the severity degree of AD, ranging from 0 for the basin of cognitively normal state to 1 for AD state. Now one can unfold the broad distribution of dementia severities and corresponding cortex regions of human brains with MCI or AD by the different severity degree.
CoViD-19, learning from the past: A wavelet and cross-correlation analysis of the epidemic dynamics looking to emergency calls and Twitter trends in Italian Lombardy region
Authors: Rivieccio Bruno Alessandro , Micheletti Alessandra , Maffeo Manuel , Zignani Matteo , Comunian Alessandro , Nicolussi Federica , Salini Silvia , Manzi Giancarlo , Auxilia Francesco , Giudici Mauro , Naldi Giovanni , Gaito Sabrina , Castaldi Silvana , Biganzoli Elia
Published: October 2020

The first case of Coronavirus Disease 2019 in Italy was detected on February the 20th in Lombardy region. Since that date, Lombardy has been the most affected Italian region by the epidemic, and its healthcare system underwent a severe overload during the outbreak. From a public health point of view, therefore, it is fundamental to provide healthcare services with tools that can reveal possible new health system stress periods with a certain time anticipation, which is the main aim of the present study. Moreover, the sequence of law decrees to face the epidemic and the large amount of news generated in the population feelings of anxiety and suspicion. Considering this whole complex context, it is easily understandable how people “overcrowded” social media with messages dealing with the pandemic, and emergency numbers were overwhelmed by the calls. Thus, in order to find potential predictors of possible new health system overloads, we analysed data both from Twitter and emergency services comparing them to the daily infected time series at a regional level. Particularly, we performed a wavelet analysis in the time-frequency plane, to finely discriminate over time the anticipation capability of the considered potential predictors. In addition, a cross-correlation analysis has been performed to find a synthetic indicator of the time delay between the predictor and the infected time series. Our results show that Twitter data are more related to social and political dynamics, while the emergency calls trends can be further evaluated as a powerful tool to potentially forecast new stress periods. Since we analysed aggregated regional data, and taking into account also the huge geographical heterogeneity of the epidemic spread, a future perspective would be to conduct the same analysis on a more local basis.
How to remove the testing bias in CoV-2 statistics
Authors: Wälde Klaus
Published: October 2020

BACKGROUND

Public health measures and private behaviour are based on reported numbers of SARS-CoV-2 infections. Some argue that testing influences the confirmed number of infections.

OBJECTIVES/METHODS

Do time series on reported infections and the number of tests allow one to draw conclusions about actual infection numbers? A SIR model is presented where the true numbers of susceptible, infectious and removed individuals are unobserved. Testing is also modelled.

RESULTS

Official confirmed infection numbers are likely to be biased and cannot be compared over time. The bias occurs because of different reasons for testing (e.g. by symptoms, representative or testing travellers). The paper illustrates the bias and works out the effect of the number of tests on the number of reported cases. The paper also shows that the positive rate (the ratio of positive tests to the total number of tests) is uninformative in the presence of non-representative testing.

CONCLUSIONS

A severity index for epidemics is proposed that is comparable over time. This index is based on Covid-19 cases and can be obtained if the reason for testing is known.
The effect of influenza vaccination on trained immunity: impact on COVID-19
Authors: Debisarun Priya A. , Struycken Patrick , Domínguez-Andrés Jorge , Moorlag Simone J.C.F.M. , Taks Esther , Gössling Katharina L. , Ostermann Philipp N. , Müller Lisa , Schaal Heiner , Oever Jaap ten , van Crevel Reinout , Netea Mihai G.
Published: October 2020

Every year, influenza causes 290.000 to 650.000 deaths worldwide and vaccination is encouraged to prevent infection in high-risk individuals. Interestingly, cross-protective effects of vaccination against heterologous infections have been reported, and long-term boosting of innate immunity (also termed trained immunity) has been proposed as the underlying mechanism. Several epidemiological studies also suggested cross-protection between influenza vaccination and COVID-19 during the current pandemic. However, the mechanism behind such an effect is unknown. Using an established in-vitro model of trained immunity, we demonstrate that the quadrivalent inactivated influenza vaccine used in the Netherlands in the 2019-2020 influenza season can induce a trained immunity response, including an improvement of cytokine responses after stimulation of human immune cells with SARS-CoV-2. In addition, we found that SARS-CoV-2 infection was less common among Dutch hospital employees who had received influenza vaccination during the 2019/2020 winter season (RR = 0,61 (95% CI, 0.4585 - 0.8195, P = 0.001). In conclusion, a quadrivalent inactivated influenza vaccine can induce trained immunity responses against SARS-CoV-2, which may result in relative protection against COVID-19. These data, coupled with similar recent independent reports, argue for a beneficial effect of influenza vaccination against influenza as well as COVID-19, and suggests its effective deployment in the 2020-2021 influenza season to protect against both infections.
Collection of 2429 constrained headshots of 277 volunteers for deep learning
Authors: Aoto Saki , Hangai Mayumi , Ueno-Yokohata Hitomi , Ueda Aki , Igarashi Maki , Ito Yoshikazu , Tsukamoto Motoko , Jinno Tomoko , Sakamoto Mika , Okazaki Yuka , Hasegawa Fuyuki , Ogata-Kawata Hiroko , Namura Saki , Kojima Kazuaki , Kikuya Masao , Matsubara Keiko , Taniguchi Kosuke , Okamura Kohji
Published: October 2020

Deep learning has rapidly been filtrating many aspects of human lives. In particular, image recognition by convolutional neural networks has inspired numerous studies in this area. Hardware and software technologies as well as large quantities of data have contributed to the drastic development of the field. However, the application of deep learning is often hindered by the need for big data and the laborious manual annotation thereof. To experience deep learning using the data compiled by us, we collected 2429 constrained headshot images of 277 volunteers. The collection of face photographs is challenging in terms of protecting personal information; we established an online procedure in which both the informed consent and image data could be obtained. We did not collect personal information, but issued agreement numbers to deal with withdrawal requests. Gender and smile labels were manually and subjectively annotated only from the appearances, and final labels were determined by majority among our team members. Rotated, trimmed, resolution-reduced, decolorized, and matrix-formed data were allowed to be publicly released. Moreover, simplified feature vectors for data sciences were released. We performed gender recognition by building convolutional neural networks based on the Inception V3 model with pre-trained ImageNet data to demonstrate the usefulness of our dataset.
Neurophysiological coding of statistical and deterministic rule information
Authors: Takács Ádám , Kóbor Andrea , Kardos Zsófia , Janacsek Karolina , Horváth Kata , Beste Christian , Németh Dezső
Published: October 2020

Humans are capable of acquiring multiple types of information presented in the same visual information stream. It has been suggested that at least two parallel learning processes are important during learning of sequential patterns – statistical learning and rule-based learning. Yet, the neurophysiological underpinnings of these parallel learning mechanisms in visual sequences are not fully understood. To differentiate between the simultaneous mechanisms at the single trial level, we apply a temporal EEG signal decomposition approach together with sLORETA source localization method to delineate whether distinct statistical and rule-based learning codes can be distinguished in EEG data and can be related to distinct functional neuroanatomical structures. We demonstrate that concomitant but distinct aspects of information coded in the N2 time window play a role in these mechanisms: mismatch detection and response control underlie statistical learning and rule-based learning, respectively, albeit with different levels of time-sensitivity. Moreover, the effects of the two learning mechanisms in the different temporally decomposed clusters of neural activity also differed from each other in neural sources. Importantly, the right inferior frontal cortex (BA44) was specifically implicated in statistical learning, confirming its role in the acquisition of transitional probabilities. In contrast, rule-based learning was associated with the prefrontal gyrus (BA6). The results show how simultaneous learning mechanisms operate at the neurophysiological level and are orchestrated by distinct prefrontal cortical areas. The current findings deepen our understanding on the mechanisms how humans are capable of learning multiple types of information from the same stimulus stream in a parallel fashion.
Somatosensory evoked potentials, indexing lateral inhibition, are modulated according to the mode of perceptual processing: comparing or combining multi-digit tactile motion
Authors: Arslanova Irena , Wang Keying , Gomi Hiroaki , Haggard Patrick
Published: October 2020

Many perceptual studies focus on the brain’s capacity to discriminate between stimuli. However, our normal experience of the world also involves integrating multiple stimuli into a single perceptual event. Neural circuit mechanisms such as lateral inhibition are believed to enhance local differences between sensory inputs from nearby regions of the receptor surface. However, this mechanism would seem dysfunctional when sensory inputs need to be combined rather than contrasted. Here, we investigated whether the brain canstrategicallyregulate the strength of suppressive interactions that underlie lateral inhibition between finger representations in human somatosensory processing. To do this, we compared sensory processing between conditions that required either comparing or combining information. We delivered two simultaneous tactile motion trajectories to index and middle fingertips of the right hand. Participants had to either compare the directions of the two stimuli, or to combine them to form their average direction. To reveal preparatory tuning of somatosensory cortex, we used an established event-related potential design to measure the interaction between cortical representations evoked by digital nerve shocks immediately before each tactile stimulus. Consistent with previous studies, we found a clear suppressive interaction between cortical activations when participants were instructed to compare the tactile motion directions. Importantly, this suppressive interaction was significantly reduced when participants had to combine the same stimuli. These findings suggest that the brain can strategically switch between a comparative and a combinative mode of somatosensory processing, according to the perceptual goal, by preparatorily adjusting the strength of a process akin to lateral inhibition.
Beta-cell specificInsrdeletion promotes insulin hypersecretion and improves glucose tolerance prior to global insulin resistance
Authors: Skovsø Søs , Panzhinskiy Evgeniy , Kolic Jelena , Cen Haoning Howard , Dionne Derek A. , Dai Xiao-Qing , Sharma Rohit B. , Elghazi Lynda , Ellis Cara E. , Faulkner Katharine , Marcil Stephanie A.M. , Overby Peter , Noursadeghi Nilou , Hutchinson Daria , Hu Xiaoke , Li Hong , Modi Honey , Wildi Jennifer S. , Botezelli J. Diego , Noh Hye Lim , Suk Sujin , Gablaski Brian , Bautista Austin , Kim Ryekjang , Cras-Méneur Corentin , Flibotte Stephane , Sinha Sunita , Luciani Dan S. , Nislow Corey , Rideout Elizabeth J. , Cytrynbaum Eric N. , Kim Jason K. , Bernal-Mizrachi Ernesto , Alonso Laura C. , MacDonald Patrick E. , Johnson James D.
Published: October 2020

Abstract

Insulin receptor (Insr) protein can be found at higher levels in pancreatic β-cells than in most other tissues, but the consequences of β-cell insulin resistance remain enigmatic.Ins1creallele was used to deleteInsrspecifically in β-cells of both female and male mice. Experimental mice were compared toIns1cre-containing littermate controls at multiple ages and on multiple diets. RNA-seq of purified recombined β-cells revealed transcriptomic consequences ofInsrloss, which differed between female and male mice. Action potential and calcium oscillation frequencies were increased inInsrknockout β- cells from female, but not male mice, whereas only male βInsrKOmice had reduced ATP-coupled oxygen consumption rate and reduced expression of genes involved in ATP synthesis. Female βInsrKOand βInsrHETmice exhibited elevated insulin release in perifusion experiments, during hyperglycemic clamps, and followingi.p.glucose challenge. Deletion ofInsrdid not alter β-cell area up to 9 months of age, nor did it impair hyperglycemia-induced proliferation. Based on our data, we adapted a mathematical model to include β-cell insulin resistance, which predicted that β-cellInsrknockout would improve glucose tolerance depending on the degree of whole-body insulin resistance. Indeed, glucose tolerance was significantly improved in female βInsrKOand βInsrHETmice when compared to controls at 9, 21 and 39 weeks, and also in insulin-sensitive 4-week old males. We did not observe improved glucose tolerance in older male mice or in high fat diet-fed mice, corroborating the prediction that global insulin resistance obscures the effects of β-cell specific insulin resistance. The propensity for hyperinsulinemia was associated with mildly reduced fasting glucose and increased body weight. We further validated our mainin vivofindings using theIns1-CreERT transgenic line and found that male mice had improved glucose tolerance 4 weeks after tamoxifen-mediatedInsrdeletion. Collectively, our data show that loss of β-cellInsrcontributes to glucose-induced hyperinsulinemia, thereby improving glucose homeostasis in otherwise insulin sensitive dietary and age contexts.
DNA methylation is required to maintain DNA replication timing precision and 3D genome integrity
Authors: Du Qian , Smith Grady C. , Luu Phuc Loi , Ferguson James M. , Armstrong Nicola J. , Caldon C. Elizabeth , Campbell Elyssa , Nair Shalima S. , Zotenko Elena , Gould Cathryn M. , Buckley Michael , Kaczorowski Dominik , Barton Kirston , Deveson Ira W. , Smith Martin A. , Powell Joseph E. , Skvortsova Ksenia , Stirzaker Clare , Achinger-Kawecka Joanna , Clark Susan J.
Published: October 2020

DNA replication timing and three-dimensional (3D) genome organisation occur across large domains associated with distinct epigenome patterns to functionally compartmentalise genome regulation. However, it is still unclear if alternations in the epigenome, in particular cancer-related DNA hypomethylation, can directly result in alterations to cancer higher order genome architecture. Here, we use Hi-C and single cell Repli-Seq, in the colorectal cancerDNMT1andDNMT3BDNA methyltransferases double knockout model, to determine the impact of DNA hypomethylation on replication timing and 3D genome organisation. First, we find that the hypomethylated cells show a striking loss of replication timing precision with gain of cell-to-cell replication timing heterogeneity and loss of 3D genome compartmentalisation. Second, hypomethylated regions that undergo a large change in replication timing also show loss of allelic replication timing, including at cancer-related genes. Finally, we observe the formation of broad ectopic H3K4me3-H3K9me3 domains across hypomethylated regions where late replication is maintained, that potentially prevent aberrant transcription and loss of genome organisation after DNA demethylation. Together, our results highlight a previously underappreciated role for DNA methylation in maintenance of 3D genome architecture.
Inhibition of SARS-CoV-2 viral entryin vitroupon blocking N- and O-glycan elaboration
Authors: Yang Qi , Hughes Thomas A. , Kelkar Anju , Yu Xinheng , Cheng Kai , Park Sheldon J. , Huang Wei-Chiao , Lovell Jonathan F. , Neelamegham Sriram
Published: October 2020

The Spike protein of SARS-CoV-2, its receptor binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated. The impact of this post-translational modification on viral entry is yet unestablished. We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus. We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding. However, these carbohydrates played a major role in regulating viral entry. Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells. Blocking O-glycan elaboration also partially blocked viral entry. Mechanistic studies suggest multiple roles for glycans during viral entry. Among them, inhibition of N-glycan biosynthesis enhanced Spike-protein proteolysis. This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry. Overall, chemical inhibitors of glycosylation may be evaluated for COVID-19.
You-Gui-Wan ameliorates house dust mite-induced allergic asthma via modulating amino acid metabolic disorder and gut dysbiosis
Authors: Hsu Wei-Hsiang , Lin Li-Jen , Chao Yen-Ming , Lu Chung-Kuang , Kao Shung-Te , Lin Yun-Lian
Published: October 2020

Introduction

Allergic asthma is a worldwide health problem, and its etiology remains incompletely understood. Besides, as current therapies for allergic asthma mainly rely on administration of glucocorticoids and have many side effects, new therapy is needed. You-Gui-Wan (YGW), a traditional Chinese herbal remedy, has been used for boosting Yang, enhancing immunity and treating allergic asthma.

Objectives

This study aims to explore the molecular changes during the development of allergic asthma and investigate the potential bio-signatures and the effect of YGW on house dust mite (HDM)-induced chronic allergic asthma in mice.

Methods

Dermatophagoides pteronyssinus (Der p), one of HDMs, was intratracheally administered once a week for a total of 7 treatments over 6 consecutive weeks to induce allergic asthma in mice. Serum metabolomics was analyzed by LC-QTOF-MS/MS. 16S rRNA-based microbiome profiling was used to analyze gut microbiota, and the correlation between metabolomic signatures and microbial community profiling was explored by Spearman correlation analysis.

Results

Serum metabolomic analysis revealed that 10 identified metabolites — acetylcarnitine, carnitine, hypoxanthine, tryptophan, phenylalanine, norleucine, isoleucine, betaine, methionine, and valine, were markedly elevated by Der p. These metabolites are mainly related to branch-chain amino acid (BCAA) metabolism, aromatic amino acid (AAA) biosynthesis, and phenylalanine metabolism. YGW administration reversed 7 of the 10 identified metabolites and chiefly affected BCAA metabolism. 16S DNA sequencing revealed that YGW profoundly changed Der p-induced gut microbiota composition. Multiple correlation analysis indicated 10 selected metabolites have a good correlation with gut microbiota.

Conclusion

Der p induced BCAA metabolic deviation in allergic asthma mice, and YGW administration effectively ameliorated the AA metabolic disorder, and improved gut dysbiosis. This study paves the way towards the interactions of Der-p on microbiome and gut microbiota, and the effects of YGW treatment as well as provides a support for YGW administration with potential benefits for allergic asthma.
GIANI: open-source software for automated analysis of 3D microscopy images
Authors: Barry David J. , Gerri Claudia , Bell Donald M. , D’Antuono Rocco , Niakan Kathy K.
Published: October 2020

The study of cellular and developmental processes in physiologically relevant three-dimensional (3D) systems facilitates an understanding of mechanisms underlying cell fate, disease and injury. While cutting-edge microscopy technologies permit the routine acquisition of 3D datasets, there is currently a limited number of open-source software packages to analyse such images. Here we describe GIANI (djpbarry.github.io/Giani), new software for the analysis of 3D images, implemented as a plugin for the popular FIJI platform. The design primarily facilitates segmentation of nuclei and cells, followed by quantification of morphology and protein expression. GIANI enables routine and reproducible batch-processing of large numbers of images and also comes with scripting and command line tools, allowing users to incorporate its functionality into their own scripts and also run GIANI on a high-performance computing cluster. We demonstrate the utility of GIANI by quantifying cell morphology and protein expression in confocal images of mouse early embryos and by segmenting nuclei from light sheet microscopy images of the flour beetle embryo. We also validate the performance of the software using simulated data. More generally, we anticipate that GIANI will be a useful tool for researchers in a variety of biomedical fields.
Androgen regulation of bowel function in mice and humans
Authors: Rastelli Daniella , Robinson Ariel , Matthews Lynley T. , Perez Kristina , Dan William , Yim Peter , Mixer Madison , Prochera Aleksandra , Hassan Rafla , Hall Kathryn , Ballou Sarah , Nee Judy , Lembo Anthony , Rao Meenakshi
Published: October 2020

Many digestive disorders have prominent sex differences in incidence, symptomatology, and treatment response that are not well understood. Irritable bowel syndrome (IBS), for example, affects approximately 10% of the population worldwide and tends to have different manifestations in males and females. Androgens are steroid hormones present at much higher levels in post-pubertal males than females and could be involved in these sex differences, but their normal functions in the bowel are largely unknown. Here, we show that gonadal androgens are required for normal gastrointestinal motilityin vivo. In the healthy mouse gut, we detected androgen receptors in smooth muscle cells and a subset of enteric neurons. Surgical or genetic disruption of androgen signaling in adult mice selectively and reversibly altered colonic motility by affecting neurons rather than smooth muscle. To determine if androgens also influence human bowel function, we measured androgen levels in 208 adults with IBS. Free testosterone levels were lower in patients with IBS compared to healthy controls and inversely correlated with symptom severity. Taken together, these observations establish a role for androgens in the regulation of colonic motility and link altered androgen signaling with a common digestive disorder. These findings advance the fundamental understanding of gut motility, with implications for normal aging and disorders involving the gut-brain axis.
Inflight head stabilization associated with wingbeat cycle and sonar emissions in the Egyptian fruit bat
Authors: Rossborough Jackson , Salles Angeles , Stidsholt Laura , Madsen Peter , Moss Cynthia F. , Hoffman Larry F.
Published: October 2020

Sensory processing of environmental stimuli during locomotion is critical for the successful execution of goal-directed behaviors and navigating around obstacles. The outcome of these sensorimotor processes can be challenged by head movements that perturb the sensory coordinate frames directing behaviors. In the case of visually-guided behaviors, visual gaze stabilization results from the integrated activity of the vestibuloocular reflex and motor efference copy originating within circuits driving locomotor behavior. A recent videographic study showed that echolocating bats exhibit inflight head stabilization during a target identification and landing task, though compensatory timing of the bats’ sonar signals was not reported. In the present investigation we tested hypotheses that head stabilization is more broadly implemented during epochs of exploratory flight, and is temporally associated with emitted sonar signals, which would optimize acoustic gaze. This was achieved by measuring head and body kinematics with motion sensors secured to the head and body of free-flying Egyptian fruit bats. These devices were integrated with ultrasonic microphones to record the bat’s sonar emissions and elucidate their temporal association with periods of head stabilization. Head accelerations in the Earth-vertical axis were asymmetric with respect to wing downbeat and upbeat relative to body accelerations. This indicated that inflight head and body accelerations were uncoupled, outcomes consistent with the implementation of head movements that limit vertical acceleration during wing downbeat. Furthermore, sonar emissions during stable flight occurred most often during wing downbeat and head stabilization, supporting the conclusion that head stabilization behavior optimized sonar gaze and environmental interrogation via echolocation.

Summary statement

Direct measurements of head and body kinematics from affixed motion sensors revealed head stabilization behaviors during exploratory flights in bats. Most sonar emissions were temporally correlated with this behavior, thereby contributing to the optimization of acoustic gaze.
The impact of open-border organization culture and employees’ knowledge, attitudes, and rewards with regards to open innovation: an empirical study
Authors: Alassaf Deemah , Dabić Marina , Shifrer Dara , Daim Tugrul
Published: October 2020

Purpose

The purpose of this paper is to fill a significant research gap in academic literature pertaining to open innovation (OI). To do so, this paper empirically tests the impact of organizational culture, employees’ knowledge, attitudes and rewards as antecedents and mediators of OI adoption in organizations, facilitating a more thorough understanding by using an empirical multi-level approach.

Design/methodology/approach

This paper analyzes the results of the “Identification of Industrial Needs for Open Innovation Education in Europe” survey through a quantitative analysis using logistic regression models. This survey includes 528 employees working in 28 different industrial sectors in 37 countries, most of which are in Europe.

Findings

The results suggest a positive impact of organizational characteristics on the adoption of OI (i.e. including the adoption of outside-in and inside-out OI activities in participating organizations), showing that the openness of an organization’s culture increases its likelihood of adopting an OI paradigm. More importantly, the results highlight the positive mediating effect of employees’ knowledge and rewards on this relationship.

Research limitations/implications

The data set that was the basis of this paper was generated in European countries, the results of the analysis are limited and appropriate for this region and may vary when applied to other regions of the world.

Practical implications

The proposed multi-level approach offers new insight into organizational knowledge. It enables the improvement of OI and knowledge management practices in organizations by assisting practitioners and academics in recognizing the relationship between organizational culture; employees’ knowledge, attitudes and rewards; and the adoption of the OI paradigm.

Social implications

This paper offers a possible explanation on why open-border cultures are more likely to have a successful OI adoption, by relating it to factors that advance in the presence of an open-border culture, such as active participation of OI relative departments in knowledge sourcing and knowledge exchange, and rewarding employees for OI activities.

Originality/value

This paper presents a new framework which links organizational culture to OI, moving on from merely examining culture in terms of its positive or negative impact on OI adoption. It contributes to research on the OI paradigm and knowledge management by highlighting the significance of antecedents and mediators from a multi-level perspective using multiple units of analysis. Most previous studies focus on a single unit of analysis.
Perceptions of wellness recovery action plan (WRAP) training: a systematic review and metasynthesis
Authors: Canacott Louise , Tickle Anna , Moghaddam Nima
Published: October 2020

Purpose

The purpose of this systematic review was to address two questions: what is the qualitative evidence for the effects of the Wellness Recovery Action Plan (WRAP) training, as perceived by adults with mental health difficulties using it? What is the quality of qualitative literature evaluating WRAP?

Design/methodology/approach

Five electronic reference databases and the EThOS database for unpublished research were systematically searched, as well as two pertinent journals. Study quality was assessed using Critical Appraisal Skills Programme criteria and results analysed using thematic synthesis.

Findings

Of 73 studies, 12 qualitative papers met inclusion criteria and were generally good quality. Analyses demonstrated expected findings, such as increased understanding and active management of mental health in the context of group processes. Results also highlighted that WRAP training promoted acceptance and improved communication with professionals. Peer delivery of WRAP was highly valued, with contrasting perceptions of peers and professionals evident. Some cultural considerations were raised by participants from ethnic minorities.

Research limitations/implications

WRAP training participation has positive self-perceived effects beyond those captured by measures of recovery. Broader implications are suggested regarding earlier access to WRAP, professional support and communication between professionals and service users. Recommendations for further research include the relationship between social support and illness self-management and peer-delivered acceptance-based approaches. Multiple time-point qualitative studies could offer insights into WRAP training processes and whether changes are sustained.

Originality/value

As the first review of qualitative evidence regarding WRAP training, value is offered both through increased understanding of outcomes and also guidance for future research.
Inhibitory role of interleukin‐10 in the cutaneous reverse Arthus reaction
Authors: Ishiura Nobuko , Yanaba Koichi , Nashiro Kiyoko , Kudo Mari , Goto Taeko , Okochi Hitoshi , Sato Shinichi
Published: October 2020

The formation and deposition of immune complexes (IC) containing immunoglobulin (Ig)G antibodies induces an acute inflammatory response with tissue injury. One of the experimental models of IC‐related vasculitis is the cutaneous reverse passive Arthus reaction, in which IgG antibodies are injected i.d., followed immediately by the i.v. application of the corresponding antigen. This reaction is characterized by edema, hemorrhage and neutrophil infiltration. To assess the role of the anti‐inflammatory cytokine interleukin (IL)‐10 in IC‐related vasculitis, we investigated the cutaneous Arthus reaction using IL‐10 knockout (IL‐10KO) mice. Edema, which was quantified macroscopically by measuring the vascular leakage of Evans blue dye at 4 h after IC challenge, was significantly increased in IL‐10KO mice compared with wild‐type mice. In addition, hemorrhage, which was assessed by the average diameter of purpuric spots at 8 h after IC challenge, was enhanced significantly in IL‐10KO mice compared with wild‐type mice. Histological examination showed that the number of extravascular neutrophils was significantly increased in IL‐10KO mice compared with wild‐type mice at 4 and 8 h after IC challenge. Analysis of pro‐inflammatory cytokine mRNA expression showed that IL‐6 mRNA levels were significantly increased in IL‐10KO mice compared with wild‐type mice at 4 and 8 h after IC challenge. These results showed that IC‐induced inflammation and vascular damage were significantly enhanced in the absence of IL‐10. Thus, IL‐10 may limit tissue disruption by suppressing the excessive infiltration of neutrophils and cytokine expression in a mouse model of type III vasculitis.
Gray‐edged line sign of scabies burrow
Authors: Ueda Takashi , Katsura Yuri , Sasaki Azusa , Minagawa Daisuke , Amoh Yasuyuki , Shirai Kyoumi
Published: October 2020

A scabies burrow is created by a mature female mite laying eggs through the stratum corneum, representing a kind of scabies eruption. We have noticed that the edges of the scabies burrow sometime appear as blackish‐gray lines. We named these lines the “gray‐edged line” sign, as a new feature of scabies burrows. The gray‐edged line sign has the following two tendencies: (i) it is rarely seen on the palm or sole; and (ii) when the burrow follows a curved course, the gray‐edged line often forms on the outer wall. Explaining the formation of this sign from clinical findings was difficult, so the aim of the present study was to elucidate the mechanisms underlying the gray‐edged line sign. This retrospective study involved collection of data from electronic medical records of patients treated for scabies in our department between April 2015 and February 2020. We treated 32 scabies patients, including 4 patients with the gray‐edged line sign. We analyzed clinical features, dermoscopy, histopathology and special stains. Fontana‐Masson staining showed melanin staining in three parts: feces; some keratinocytes around the scabies burrows; and the mouth and legs of the scabies mite. The gray‐edged line sign appears to represent mite feces containing melanin.