bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Temperature on Development and Survival of NymphalLycorma delicatula(Hemiptera: Fulgoridae)
Authors: Kreitman Devin , Keena Melody A , Nielsen Anne L , Hamilton George
Published: October 2020

Lycorma delicatula (White), an invasive planthopper originally from Asia, is an emerging pest in North America. It is important to understand its phenology in order to determine its potential range in the United States. Lycorma delicatula nymphs were reared on Ailanthus altissima (Miller) (Sapindales: Simaroubaceae) at each of the following constant temperatures: 5, 10, 15, 20, 25, 30, 35, and 40°C. The time spent in each instar and survival was recorded. Developmental rate increased with temperature from 15 to 30°C for all instars, then declined again at higher temperatures. Nymphal survival was lower at 35°C than between 15 and 30°C for all instars, and first instars placed at 5, 10, and 40°C all died without molting. This suggests that L. delicatula survival and development may be affected in the Southern United States by high temperatures and developmental delays will occur under cool spring conditions. The lower developmental threshold was found to be 13.00 ± 0.42°C for first instars, 12.43 ± 2.09°C for second instars, 8.48 ± 2.99°C for third instars, and 6.29 ± 2.12°C for fourth instars. The degree-day (DD) requirement for nymphs in the previous instar to complete development to reach the second instar, third instar, fourth instar, and adult was 166.61, 208.75, 410.49, and 620.07 DD (base varied), respectively. These results provide key data to support the development of phenology models and help identify the potential range of L. delicatula in North America.
Computed tomography imaging needs for novel transcatheter tricuspid valve repair and replacement therapies
Authors: Hell Michaela M , Emrich Tilman , Kreidel Felix , Kreitner Karl-Friedrich , Schoepf U Joseph , Münzel Thomas , von Bardeleben Ralph Stephan
Published: October 2020

Transcatheter tricuspid valve therapies are an emerging field in structural heart interventions due to the rising number of patients with severe tricuspid regurgitation and the high risk for surgical treatment. Computed tomography (CT) allows exact measurements of the annular plane, evaluation of adjacent structures, assessment of the access route, and can also be used to identify optimal fluoroscopic projection planes to enhance periprocedural imaging. This review provides an overview of current transcatheter tricuspid valve repair and replacement therapies and to what extent CT can support these interventions.
A scoping review of qualitative research on perceptions of one’s own alcohol use
Authors: Morris Stephanie , Stewart Duncan , Madden Mary , McCambridge Jim
Published: October 2020

Background

This scoping review aims to map the extent, range and nature of qualitative research on people’s ‘perceptions’ of their own alcohol consumption.

Methods

A systematic search of five electronic databases was conducted. A total of 915 abstracts were screened and 452 full texts examined, of which 313 papers met the inclusion criteria (including a report of qualitative data on perceptions, experiences or views of people’s own drinking in peer-reviewed journals published in English).

Results

This study maps the available literature assembled over approximately 30 years, which was found to be extensive and diverse. Many existing studies are focused largely on people’s ‘experiences’ of their own drinking behaviours, particularly when they were drinking in ways commonly understood as heavy, risky or problematic. Fewer studies focused on populations whose drinking was not heavy or was risky in less obvious ways, such as older adults prescribed medications for chronic health conditions. Most studies were conducted since 2010, with the rate of publications increasing since 2014.

Conclusions

This review identifies gaps in the evidence regarding people’s perceptions of their own drinking and opportunities for qualitative studies to make valuable contributions to alcohol research. Gaps discussed include patterns of drinking that are less obviously problematic, and in relation to consumption of alcohol in those parts of the world where overall consumption and harms from alcohol are high. Such studies could usefully be informed by existing studies in the evidence mapping.
A Direct Measure of Stand Density Based on Stand Growth
Authors: Dean Thomas J , D’Amato Anthony W , Palik Brian J , Battaglia Mike A , Harrington Constance A
Published: October 2020

Standardizing gross volume increment on periodic height increment of the dominant trees is a means of minimizing the effects of site quality and age in growth–growing-stock relations; however, volume increment per height increment contains more information than just a normalization method for fitting growth models. This study builds on previous work suggesting that the cumulative sum of the ratios between individual-tree volume increment and height increment may be a direct measure of stand density. We used data from several levels of growing-stock studies for Douglas-fir, ponderosa pine, and red pine to explore this hypothesis. Regression analysis indicated that the sum of the ratios is proportional to(Dqx⋅N), the underlying equation form of Reineke’s stand density index. Stem growth is a function of canopy dynamics, and additional analyses showed that volume added per unit of height growth was also related to canopy architecture, increasing with decreasing live-crown ratio and increasing foliage density. The linkages between growth, canopy architecture, intermediary canopy dynamics, and (Dqx⋅N) support the hypothesis that the sum of the tree ratios between volume increment and height increment is a direct measure of site occupancy due to its association between growth and corresponding resource use.
Prediction of single-cell gene expression for transcription factor analysis
Authors: Behjati Ardakani Fatemeh , Kattler Kathrin , Heinen Tobias , Schmidt Florian , Feuerborn David , Gasparoni Gilles , Lepikhov Konstantin , Nell Patrick , Hengstler Jan , Walter Jörn , Schulz Marcel H
Published: October 2020

Background

Single-cell RNA sequencing is a powerful technology to discover new cell types and study biological processes in complex biological samples. A current challenge is to predict transcription factor (TF) regulation from single-cell RNA data.

Results

Here, we propose a novel approach for predicting gene expression at the single-cell level using cis-regulatory motifs, as well as epigenetic features. We designed a tree-guided multi-task learning framework that considers each cell as a task. Through this framework we were able to explain the single-cell gene expression values using either TF binding affinities or TF ChIP-seq data measured at specific genomic regions. TFs identified using these models could be validated by the literature.

Conclusion

Our proposed method allows us to identify distinct TFs that show cell type–specific regulation. This approach is not limited to TFs but can use any type of data that can potentially be used in explaining gene expression at the single-cell level to study factors that drive differentiation or show abnormal regulation in disease. The implementation of our workflow can be accessed under an MIT license via https://github.com/SchulzLab/Triangulate.
Toward quantitative electromagnetic field imaging by differential-phase-contrast scanning transmission electron microscopy
Authors: Seki Takehito , Ikuhara Yuichi , Shibata Naoya
Published: October 2020

Differential-phase-contrast scanning transmission electron microscopy (DPC STEM) is a technique to directly visualize local electromagnetic field distribution inside materials and devices at very high spatial resolution. Owing to the recent progress in the development of high-speed segmented and pixelated detectors, DPC STEM now constitutes one of the major imaging modes in modern aberration-corrected STEM. While qualitative imaging of electromagnetic fields by DPC STEM is readily possible, quantitative imaging by DPC STEM is still under development because of the several fundamental issues inherent in the technique. In this report, we review the current status and future prospects of DPC STEM for quantitative electromagnetic field imaging from atomic scale to mesoscopic scale.
“They’re Constantly Cycling Through”: Lessons about Turnover and Collaborative Forest Planning
Authors: Coleman Kimberly J , Butler William H , Stern Marc J , Beck Samantha L
Published: October 2020

Within forest planning and management, collaboration has becoming increasingly widespread. Many collaborative projects take place over long time periods, and thus personnel turnover is inevitable within these groups. Scholars from the fields of business and organizational science have long studied strategies that organizations can use to prepare for and address turnover successfully. We draw from that literature and use it to examine the Collaborative Forest Landscape Restoration Program (CFLRP), a federal program aimed at bringing diverse stakeholders together to address the increasing costs, severity, and prevalence of wildfires in the United States. We conducted qualitative analysis of interviews, archival documents, and memos to explore what strategies are used within CFLRP groups to address turnover. We discuss our findings in light of the existing literature from business and organizational science and present insights about which strategies may be adaptable to collaborative natural resource management and which may require further research to assess their applicability to collaborative groups.
Phenotypic Plasticity Contributes to Maize Adaptation and Heterosis
Authors: Liu Nannan , Du Yuanhao , Warburton Marilyn L , Xiao Yingjie , Yan Jianbing
Published: October 2020

Plant phenotypic plasticity describes altered phenotypic performance of an individual when grown in different environments. Exploring genetic architecture underlying plant plasticity variation may help mitigate the detrimental effects of a rapidly changing climate on agriculture, but little research has been done in this area to date. In the present study, we established a population of 976 maize F1 hybrids by crossing 488 diverse inbred lines with two elite testers. Genome-wide association study identified hundreds of quantitative trait loci associated with phenotypic plasticity variation across diverse F1 hybrids, the majority of which contributed very little variance, in accordance with the polygenic nature of these traits. We identified several quantitative trait locus regions that may have been selected during the tropical-temperate adaptation process. We also observed heterosis in terms of phenotypic plasticity, in addition to the traditional genetic value differences measured between hybrid and inbred lines, and the pattern of which was affected by genetic background. Our results demonstrate a landscape of phenotypic plasticity in maize, which will aid in the understanding of its genetic architecture, its contribution to adaptation and heterosis, and how it may be exploited for future maize breeding in a rapidly changing environment.
Characterizing benefit from temozolomide in MGMT promoter unmethylated and methylated glioblastoma: a systematic review and meta-analysis
Authors: Alnahhas Iyad , Alsawas Mouaz , Rayi Appaji , Palmer Joshua D , Raval Raju , Ong Shirley , Giglio Pierre , Murad Mohammad Hassan , Puduvalli Vinay
Published: October 2020

Background

The current standard of care for the management of patients with newly diagnosed glioblastoma (GBM) includes maximal safe resection followed by radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). While it is well established that TMZ has better efficacy in patients with MGMT promoter methylation, it remains an area of debate whether TMZ should be omitted when treating GBM patients with unmethylated MGMT.

Methods

We conducted a systematic review and meta-analysis to provide separate estimates of median overall survival (OS) and progression-free survival (PFS) for patients with methylated and unmethylated GBM treated with RT with or without TMZ. We searched multiple databases from inception to January 13, 2020.

Results

The median OS for patients with unmethylated GBM treated with RT/TMZ pooled from 5 phase III studies (N = 655) was 14.11 months (95% confidence interval [CI], 13.18–15.04) with a median PFS of 4.99 months (95% CI, 4.25–5.72). In contrast, the median OS for patients with methylated GBM pooled from 6 studies (N = 753) was 24.59 months (95% CI, 22.19–26.99) with a median PFS pooled from 7 studies (N = 805) of 9.51 months (95% CI, 7.41–11.61). There is a paucity of prospective data pertaining to OS/PFS in unmethylated patients treated with RT only and therefore a direct comparison was not possible.

Conclusions

This meta-analysis provides estimates of survival for patients with MGMT methylated or unmethylated GBM treated with RT/TMZ. Further research is needed to delineate whether TMZ should be withheld for patients with unmethylated GBM outside of the setting of clinical trials.
Effects of drought on nitrogen uptake and carbon dynamics in trees
Authors: Joseph Jobin , Luster Jörg , Bottero Alessandra , Buser Nathalie , Baechli Lukas , Sever Krunoslav , Gessler Arthur
Published: October 2020

Research on drought impact on tree functioning is focussed primarily on water and carbon (C) dynamics. Changes in nutrient uptake might also affect tree performance under drought and there is a need to explore underlying mechanisms. We investigated effects of drought on (a) in situ nitrogen (N) uptake, accounting for both, N availability to fine roots in soil and actual N uptake, (b) physiological N uptake capacity of roots and (c) the availability of new assimilates to fine roots influencing the N uptake capacity using 15N and 13C labelling. We assessed saplings of six different tree species (Acer pseudoplatanus L., Fagus sylvatica L., Quercus petraea (Mattuschka) Liebl., Abies alba Mill., Picea abies (L.) H.Karst. and Pinus sylvestris L.). Drought resulted in significant reduction of in situ soil N uptake in deciduous trees accompanied by reduced C allocation to roots and by a reduction in root biomass available for N uptake. Although physiological root N uptake capacity was not affected by drought in deciduous saplings, reduced maximum ammonium but not nitrate uptake was observed for A. alba and P. abies. Our results indicate that drought has species-specific effects on N uptake. Even water limitations of only 5 weeks as assessed here can decrease whole-plant inorganic N uptake, independent of whether the physiological N uptake capacity is affected or not.
HIV-1 p24Gag adaptation to modern and archaic HLA-allele frequency differences in ethnic groups contributes to viral subtype diversification
Authors: Kist Nicolaas C , Lambert Ben , Campbell Samuel , Katzourakis Aris , Lunn Daniel , Lemey Philippe , Iversen Astrid K N
Published: October 2020

Pathogen-driven selection and past interbreeding with archaic human lineages have resulted in differences in human leukocyte antigen (HLA)-allele frequencies between modern human populations. Whether or not this variation affects pathogen subtype diversification is unknown. Here we show a strong positive correlation between ethnic diversity in African countries and both human immunodeficiency virus (HIV)-1 p24gag and subtype diversity. We demonstrate that ethnic HLA-allele differences between populations have influenced HIV-1 subtype diversification as the virus adapted to escape common antiviral immune responses. The evolution of HIV Subtype B (HIV-B), which does not appear to be indigenous to Africa, is strongly affected by immune responses associated with Eurasian HLA variants acquired through adaptive introgression from Neanderthals and Denisovans. Furthermore, we show that the increasing and disproportionate number of HIV-infections among African Americans in the USA drive HIV-B evolution towards an Africa-centric HIV-1 state. Similar adaptation of other pathogens to HLA variants common in affected populations is likely.
Iris trauma in a highly myopic woman with one functional eye October consultation #1
Authors: Menapace Rupert
Published: October 2020

A 58-year-old highly myopic woman had suffered a windscreen trauma to her left eye during a car accident 40 years earlier. Reportedly, iris tissue was removed in emergency surgery. Her right eye has very poor vision with only hand motion perception due to myopic maculopathy. The myopia of −12 diopters (D) in her left eye is corrected with a hard contact lens, which is well tolerated. With the contact lens and an additional spectacle correction of −1.5 D, visual acuity is 0.5 Jg1. Slitlamp biomicroscopy reveals a lacerated iris with iridodialysis extending along the superior circumference from 8:30 to 4:30 o'clock and a superior–temporal pupil coloboma. The disinserted and contracted iris tissue resides on the anterior lens surface (Figure 1). The residual pupil is slightly decentered inferiorly and still reactive to light. The lens zonular fibers are intact along the full and particularly the superior circumference. Slitlamp illumination reveals grade 2 cataract formation in nucleus center. Intraocular pressure is 12 mm Hg. The central retina shows myopic tabulation with intact macula.

During the past 6 months, the patient has been experiencing increasing shortsightedness and light sensitivity, especially outdoors, and desires cataract surgery. Given this is the only eye with reading capacity, which would be your surgical options and preferred approach to treat the cataract and remedy the traumatized iris?
Culicoidibacter larvae gen. nov., sp. nov., from the gastrointestinal tract of the biting midge (Culicoides sonorensis) larva, belongs to a novel lineage Culicoidibacteraceae fam. nov., Culicoidibacterales ord. nov. and Culicoidibacteria classis nov. of the phylum Firmicutes
Authors: Neupane Saraswoti , Ghosh Anuradha , Gunther Sebastian , Martin Karin , Zurek Ludek
Published: October 2020

Strain CS-1T, a novel facultative anaerobic bacterium, was isolated from the larval gastrointestinal tract of the biting midge, Culicoides sonorensis, a vector of the epizootic haemorrhagic disease virus and the bluetongue virus. Cells were Gram-stain-positive, non-motile, non-spore-forming, pleomorphic rods. Optimal growth occurred at pH 7.5 and 37 °C. The G+C content of the genomic DNA was 38.3 mol%, estimated by using HPLC. The dominant cellular fatty acids were C14 : 0 (45.9 %) and C16 : 0 (26.6 %). The polar lipid profile comprised glycolipids, diphosphatidylglycerol, phospholipids and phosphoglycolipids. Respiratory quinones were not detected. Strain CS-1T had very low 16S rRNA gene similarity to members of the phylum

Firmicutes

:

Macrococcus canis

KM45013T (85 % similarity) and

Turicibacter sanguinis

MOL361T (88 % similarity). Phylogenetic analysis based on 16S rRNA, rpoB, gyrB genes, and conserved protein sequences of the whole genome revealed that strain CS-1T was related to members of the classes

Bacilli

and

Erysipelotrichia

within the phylum

Firmicutes

. Furthermore, average nucleotide identity and digital DNA–DNA hybridization analyses of the whole genome revealed very low sequence similarity to species of

Bacilli

and

Erysipelotrichaceae

(

Macrococcus canis

KM45013T and

Turicibacter

sp. H121). These results indicate that strain CS-1T belongs to the phylum

Firmicutes

and represents a new species of a novel genus, family, order and class. Based on the phenotypic, chemotaxonomic, phylogenetic and genomic characteristics, we propose the novel taxon Culicoidibacter larvae gen. nov., sp. nov. with the type strain CS-1T (=CCUG 71726T=DSM 106607T) within the hereby new proposed novel family Culicoidibacteraceae fam. nov., new order Culicoidibacaterales ord. nov. and new class Culicoidibacteria classis nov. in the phylum

Firmicutes

.
Interpreting chest X-rays via CNNs that exploit disease dependencies and uncertainty labels
Authors: Pham Hieu H. , Le Tung T. , Tran Dat Q. , Ngo Dat T. , Nguyen Ha Q.
Published: October 2020

Chest radiography is one of the most common types of diagnostic radiology exams, which is critical for screening and diagnosis of many different thoracic diseases. Specialized algorithms have been developed to detect several specific pathologies such as lung nodule or lung cancer. However, accurately detecting the presence of multiple diseases from chest X-rays (CXRs) is still a challenging task. This paper presents a supervised multi-label classification framework based on deep convolutional neural networks (CNNs) for predicting the risk of 14 common thoracic diseases. We tackle this problem by training state-of-the-art CNNs that exploit dependencies among abnormality labels. We also propose to use the label smoothing technique for a better handling of uncertain samples, which occupy a significant portion of almost every CXR dataset. Our model is trained on over 200,000 CXRs of the recently released CheXpert dataset and achieves a mean area under the curve (AUC) of 0.940 in predicting 5 selected pathologies from the validation set. This is the highest AUC score yet reported to date. The proposed method is also evaluated on the independent test set of the CheXpert competition, which is composed of 500 CXR studies annotated by a panel of 5 experienced radiologists. The performance is on average better than 2.6 out of 3 other individual radiologists with a mean AUC of 0.930, which ranks first on the CheXpert leaderboard at the time of writing this paper.
Screening for early-stage Alzheimer’s disease using optimized feature sets and machine learning
Authors: Kleiman Michael J. , Barenholtz Elan , Galvin James E. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2020

Background

Detecting early-stage Alzheimer’s disease in clinical practice is difficult due to a lack of efficient and easily administered cognitive assessments that are sensitive to very mild impairment, a likely contributor to the high rate of undetected dementia.

Objective

Here, we aim to identify groups of cognitive assessment features optimized for detecting mild impairment that can be used in routine screening. We also compare the efficacy of classifying impairment using either a two-class (impaired vs non-impaired) or three-class approach.

Methods

Supervised feature selection methods generated groups of cognitive measurements targeting impairment defined at CDR 0.5 and above. Random forest classifiers then generated predictions of impairment for each group using highly stochastic cross-validation, with group outputs examined using general linear models.

Results

The strategy of combining impairment levels for two-class classification resulted in significantly higher sensitivities and NPVs, two metrics useful in clinical screening, compared to the three-class approach. Just four neuropsychological features (delayed WAIS Logical Memory, trail-making, patient and informant memory questions), able to be administered in approximately 15 active minutes (∼30 minutes with delay), enabled classification sensitivity of 94.53% (88.43% PPV) with the addition of four more features significantly increasing sensitivity to 95.18% (88.77% PPV) when added to the model as a second classifier.

Conclusion

The high detection rate paired with the minimal assessment time of the four identified features may act as an effective starting point when screening for cognitive impairment defined at CDR 0.5 and above.
Defining a master curve of abdominal aortic aneurysm growth and its potential utility of clinical management
Authors: Akkoyun Emrah , Gharahi Hamidreza , Kwon Sebastian T. , Zambrano Byron A. , Rao Akshay , Acar Aybar C. , Lee Whal , Baek Seungik
Published: October 2020

Objective

The maximum diameter measurement of an abdominal aortic aneurysm (AAA), which depends on orthogonal and axial cross-sections or maximally inscribed spheres within the AAA, plays a significant role in the clinical decision making process. This study aims to build a large dataset of morphological parameters from longitudinal CT scans and analyze their correlations. Furthermore, this work explores the existence of a “master curve” of AAA growth, and tests which parameters serve to enhance its predictability for clinical use.

Methods

106 CT scan images from 25 Korean AAA patients were retrospectively obtained. We subsequently computed morphological parameters, growth rates, and pair-wise correlations, and attempted to enhance the predictability of the growth for high-risk aneurysms using non-linear curve fitting and least-square minimization.

Results

An exponential AAA growth model was fitted to the maximum spherical diameter, as the best representative of the growth among all parameters (r-square: 0.985) and correctly predicted to 74 of 79 scans based on a 95% confidence interval. AAA volume expansion rateswere highly correlated (r=0.80) with thrombus accumulation rates.

Conclusions

The exponential growth model using spherical diameter provides useful information about progression of aneurysm size and enables AAA growth rate extrapolation during a given surveillance period.
Projected COVID-19 epidemic in the United States in the context of the effectiveness of a potential vaccine and implications for social distancing and face mask use
Authors: Shen Mingwang , Zu Jian , Fairley Christopher K. , Pagán José A. , An Li , Du Zhanwei , Guo Yuming , Rong Libin , Xiao Yanni , Zhuang Guihua , Li Yan , Zhang Lei
Published: October 2020

Background

Multiple candidates of COVID-19 vaccines have entered Phase III clinical trials in the United States (US). There is growing optimism that social distancing restrictions and face mask requirements could be eased with widespread vaccine adoption soon.

Methods

We developed a dynamic compartmental model of COVID-19 transmission for the four most severely affected states (New York, Texas, Florida, and California). We evaluated the vaccine effectiveness and coverage required to suppress the COVID-19 epidemic in scenarios when social contact was to return to pre-pandemic levels and face mask use was reduced. Daily and cumulative COVID-19 infection and death cases were obtained from the Johns Hopkins University Coronavirus resource center and used for model calibration.

Results

Without a vaccine, the spread of COVID-19 could be suppressed in these states by maintaining strict social distancing measures and face mask use levels. But relaxing social distancing restrictions to the pre-pandemic level without changing the current face mask use would lead to a new COVID-19 outbreak, resulting in 0.8-4 million infections and 15,000-240,000 deaths across these four states over the next 12 months. In this scenario, introducing a vaccine would partially offset this negative impact even if the vaccine effectiveness and coverage are relatively low. However, if face mask use is reduced by 50%, a vaccine that is only 50% effective (weak vaccine) would require coverage of 55-94% to suppress the epidemic in these states. A vaccine that is 80% effective (moderate vaccine) would only require 32-57% coverage to suppress the epidemic. In contrast, if face mask usage stops completely, a weak vaccine would not suppress the epidemic, and further major outbreaks would occur. A moderate vaccine with coverage of 48-78% or a strong vaccine (100% effective) with coverage of 33-58% would be required to suppress the epidemic. Delaying vaccination rollout for 1-2 months would not substantially alter the epidemic trend if the current interventions are maintained.

Conclusions

The degree to which the US population can relax social distancing restrictions and face mask use will depend greatly on the effectiveness and coverage of a potential COVID-19 vaccine if future epidemics are to be prevented. Only a highly effective vaccine will enable the US population to return to life as it was before the pandemic.
Clinical Suspicion of COVID-19 in Nursing Home residents: symptoms and mortality risk factors
Authors: Rutten Jeanine J.S. , van Loon Anouk M. , van Kooten Janine , van Buul Laura W. , Joling Karlijn J. , Smalbrugge Martin , Hertogh Cees M.P.M.
Published: October 2020

Objectives

To describe symptomatology, mortality and risk factors for mortality in a large group of Dutch nursing home (NH) residents with clinically-suspected COVID-19 who were tested with a Reverse Transcription Polymerase Chain Reaction (RT-PCR) test.

Design

Prospective cohort study.

Setting and participants

Residents of Dutch NHs with clinically-suspected COVID-19 and who received RT-PCR test.

Methods

We collected data of NH residents with clinically-suspected COVID-19, via electronic health records between March 18th and May 13th, 2020. Registration was performed on diagnostic status (confirmed (COVID-19+)/ruled out (COVID-19-)) and symptomatology (typical and atypical symptoms). Information on mortality and risk factors for mortality were extracted from usual care data.

Results

In our sample of residents with clinically-suspected COVID-19 (N=4007), COVID-19 was confirmed in 1538 residents (38%). Although, symptomatology overlapped between residents with COVID-19+ and COVID-19-, those with COVID-19+ were three times more likely to die within 30 days (hazard ratio (HR), 3·1; 95% CI, 2·7 to 3·6). Within this group, mortality was higher for men than for women (HR, 1·8; 95%, 1·5-2·2) and we observed a higher mortality for residents with dementia, reduced kidney function, and Parkinson’s Disease, even when corrected for age, gender, and comorbidities.

Conclusions and implications

About 40% of the residents with clinically-suspected COVID-19 actually had COVID-19, based on the RT-PCR test. Despite an overlap in symptomatology, mortality rate was three times higher for residents with COVID-19+. This emphasizes the importance of using low-threshold testing in NH residents which is an essential prerequisite to using limited personal protective equipment and isolation measures efficiently.
The Risk of Indoor Sports and Culture Events for the Transmission of COVID-19 (Restart-19)
Authors: Moritz Stefan , Gottschick Cornelia , Horn Johannes , Popp Mario , Langer Susan , Klee Bianca , Purschke Oliver , Gekle Michael , Ihling Angelika , Mikolajczyk Rafael
Published: October 2020

Nearly all mass gathering events (MGEs) worldwide have been banned since the outbreak of SARS-CoV-2 as they are supposed to pose a considerable risk for transmission of COVID-19. We investigated transmission risk of SARS-CoV-2 by droplets and aerosols during an experimental indoor MGE (using N95 masks and contact tracing devices) and conducted a simulation study to estimate the resulting burden of disease under conditions of controlled epidemics. The number of exposed contacts was <10 for scenarios with hygiene concept and good ventilation, but substantially higher otherwise. Of subsequent cases, 0%-23% were attributable to MGEs. Overall, the expected additional effect of indoor MGEs on burden of infections is low if hygiene concepts are applied and adequate ventilation exists.

One Sentence Summary

Seated indoor events, when conducted under hygiene precautions and with adequate ventilation, have small effects on the spread of COVID-19.
Rapid Support for Older Adults during the initial stages of the COVID-19 Pandemic: Results from a Geriatric Psychiatry helpline
Authors: Wahl Anna-Sophia , Benson Gloria S. , Hausner Lucrezia , Schmitt Sandra , Knoll Annika , Bondy Adriana Feretti , Hefter Dimitri , Frölich Lutz
Published: October 2020

Background

The COVID-19 pandemic and governmental lockdown measures disproportionally impacts older adults. This study presents the results from a psychiatric helpline for older adults in Mannheim, Germany, during the lockdown, set up to provide information and psychosocial support measures. We aim to elucidate the needs of older adults, their reported changes and the psychological impact during the initial stages of the health crisis.

Methods

55 older adults called the psychiatric helpline between April and June 2020. Information on demographics, previous diagnosis of psychiatric and somatic diseases as well as changes in daily life due to the pandemic was collected anonymously. Current mental health status was assessed using the depression HAMD-7 and the anxiety HAM-A scales.

Results

Most callers were women, older adults (M = 74.69 years), single and retired. 69% of callers reported new or an increase in psychiatric symptoms, with anxiety and depressive symptoms being the most common ones. Age was significantly negatively correlated to higher levels of anxiety and depression symptoms. Individuals with a previous diagnosis of a psychiatric disease reported significantly higher levels of depressive and anxiety symptoms than those without a diagnosis.

Conclusion

In older adults, the perceived psychological impact of the COVID-19 crisis appears to ameliorate with age. Individuals with a history of psychiatric disease are most vulnerable to negative mental health outcomes. Rapid response in the form of a geriatric helpline are useful initiatives to support the needs and the psychological well-being of older adults during a health crisis.
Cognitive screening instruments for dementia: comparing metrics of test limitation
Authors: Larner Andrew J
Published: October 2020

Cognitive screening instruments (CSIs) for dementia and mild cognitive impairment are usually characterised in terms of measures of discrimination such as sensitivity, specificity, and likelihood ratios. However, CSIs also have limitations. Several metrics exist which may be used to denote test limitations but they are seldom examined. Data from several pragmatic test accuracy studies of CSIs were interrogated to calculate various measures of limitation, namely: misclassification rate; net harm to net benefit ratio; and the likelihood to be diagnosed or misdiagnosed. Intra- and inter-test performance for measures of discrimination and limitation were compared. The study found that some tests with very high sensitivity but low specificity for dementia fared poorly on measures of limitation, with high misclassification rates, low net harm to net benefit ratios, and low likelihoods to be diagnosed or misdiagnosed; some had likelihoods favouring misdiagnosis over diagnosis. Tests with a better balance of sensitivity and specificity fared better on measures of limitation. When choosing which CSIs to administer, measures of test limitation should be considered as well as measures of test discrimination. Although high test sensitivity may be desirable to avoid false negatives, false positives also have a cost. Identification of tests having high misclassification rate, low net harm to net benefit ratio, and low likelihood to be diagnosed or misdiagnosed, may have implications for their use in clinical practice.
Phase separation of the LINE-1 ORF1 protein is mediated by the N-terminus and coiled-coil domain
Authors: Newton JC , Li GY , Naik MT , Fawzi NL , Sedivy JM , Jogl G
Published: October 2020

Long Interspersed Nuclear Element-1 (LINE-1 or L1) is a retrotransposable element that autonomously replicates in the human genome, resulting in DNA damage and genomic instability. Activation of L1 in senescent cells triggers a type I interferon response and age-associated inflammation. Two open reading frames encode an ORF1 protein functioning as mRNA chaperone and an ORF2 protein providing catalytic activities necessary for retrotransposition. No function has been identified for the conserved, disordered N-terminal region of ORF1. Using microscopy and NMR spectroscopy, we demonstrate that ORF1 forms liquid droplets in vitro in a salt-dependent manner and that interactions between its N-terminal region and coiled-coil domain are necessary for phase separation. Mutations disrupting blocks of charged residues within the N-terminus impair phase separation while some mutations within the coiled-coil domain enhance phase separation. Demixing of the L1 particle from the cytosol may provide a mechanism to protect the L1 transcript from degradation.

Statement of significance

Over half of the human genome is comprised of repetitive sequences. The Long Interspersed Nuclear Element-1 (L1) is an autonomous mobile DNA element that can alter its genomic location, resulting in genomic instability and DNA damage. L1 encodes two proteins that are required for this function: the ORF1 RNA chaperone and the enzymatic ORF2. Here, we demonstrate that ORF1 forms liquid-liquid phase separated states in vitro, which is mediated by electrostatic interactions between the conserved, disordered N-terminus and coiled-coil domain. This work provides a framework to explore how L1 phase separation may enhance the ability of the retrotransposable element to colonize the genome by preventing degradation of the L1 transcript and evasion of host immune responses.
MiSebastes: An eDNA metabarcoding primer set for rockfishes (genusSebastes)
Authors: Min Markus A. , Barber Paul H. , Gold Zachary
Published: October 2020

Environmental DNA (eDNA) is a promising biomonitoring tool for marine ecosystems, but its effectiveness for North Pacific coastal fishes is limited by the inability of existing barcoding primers to differentiate among rockfishes in the genusSebastes.Comprised of 110 commercially and ecologically important species, this recent radiation is exceptionally speciose, and exhibits high sequence similarity among species at standard barcoding loci. Here, we report newSebastes-specific metabarcoding primers that target mitochondrialcytochrome B.Amongst the 110Sebastesspecies, 85 unique barcodes (of which 62 are species-specific) were identified in our amplicon region based on available reference sequences. The majority of the remaining barcodes are shared by only two species. Importantly, MiSebastes yield unique barcodes for 28 of 44 commercially harvested species in California, a dramatic improvement compared to the widely employed MiFish12Sprimers which only recover one of 44. Tests of these primers in an aquarium mesocosm containing 16 rockfish species confirms the utility of these new primers for eDNA metabarcoding, providing an important biomonitoring tool for these key coastal marine fishes.
Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes
Authors: Karki Rajendra , Sharma Bhesh Raj , Tuladhar Shraddha , Williams Evan Peter , Zalduondo Lillian , Samir Parimal , Zheng Min , Sundaram Balamurugan , Banoth Balaji , Malireddi R. K. Subbarao , Schreiner Patrick , Neale Geoffrey , Vogel Peter , Webby Richard , Jonsson Colleen Beth , Kanneganti Thirumala-Devi
Published: October 2020

The COVID-19 pandemic has caused significant morbidity and mortality. Currently, there is a critical shortage of proven treatment options and an urgent need to understand the pathogenesis of multi-organ failure and lung damage. Cytokine storm is associated with severe inflammation and organ damage during COVID-19. However, a detailed molecular pathway defining this cytokine storm is lacking, and gaining mechanistic understanding of how SARS-CoV-2 elicits a hyperactive inflammatory response is critical to develop effective therapeutics. Of the multiple inflammatory cytokines produced by innate immune cells during SARS-CoV-2 infection, we found that the combined production of TNF-α and IFN-γ specifically induced inflammatory cell death, PANoptosis, characterized by gasdermin-mediated pyroptosis, caspase-8-mediated apoptosis, and MLKL-mediated necroptosis. Deletion of pyroptosis, apoptosis, or necroptosis mediators individually was not sufficient to protect against cell death. However, cells deficient in both RIPK3 and caspase-8 or RIPK3 and FADD were resistant to this cell death. Mechanistically, the JAK/STAT1/IRF1 axis activated by TNF-α and IFN-γ co-treatment induced iNOS for the production of nitric oxide. Pharmacological and genetic deletion of this pathway inhibited pyroptosis, apoptosis, and necroptosis in macrophages. Moreover, inhibition of PANoptosis protected mice from TNF-α and IFN-γ-induced lethal cytokine shock that mirrors the pathological symptoms of COVID-19. In vivo neutralization of both TNF-α and IFN-γ in multiple disease models associated with cytokine storm showed that this treatment provided substantial protection against not only SARS-CoV-2 infection, but also sepsis, hemophagocytic lymphohistiocytosis, and cytokine shock models, demonstrating the broad physiological relevance of this mechanism. Collectively, our findings suggest that blocking the cytokine-mediated inflammatory cell death signaling pathway identified here may benefit patients with COVID-19 or other cytokine storm-driven syndromes by limiting inflammation and tissue damage. The findings also provide a molecular and mechanistic description for the term cytokine storm. Additionally, these results open new avenues for the treatment of other infectious and autoinflammatory diseases and cancers where TNF-α and IFN-γ synergism play key pathological roles.
The H2A.J histone variant contributes to Interferon-Stimulated Gene expression in senescence by its weak interaction with H1 and the derepression of repeated DNA sequences
Authors: Mangelinck Adele , Coudereau Clement , Courbeyrette Regis , Ouararhni Khalid , Hamiche Ali , Redon Christophe E. , Bonner William M. , Van Dijk Erwin , Derbois Celine , Olaso Robert , Deleuze Jean-Francois , Fenaille Francois , Ruebe Claudia E. , Thuret Jean-Yves , MANN Carl
Published: October 2020

The histone variant H2A.J was previously shown to accumulate in senescent human fibroblasts with persistent DNA damage to promote inflammatory gene expression, but its mechanism of action was unknown. We show that H2A.J accumulation contributes to weakening the association of histone H1 to chromatin and increasing its turnover. Decreased H1 in senescence is correlated with increased expression of some repeated DNA sequences, increased expression of STAT/IRF transcription factors, and transcriptional activation of Interferon-Stimulated Genes (ISGs). The H2A.J-specific Val-11 moderates the transcriptional activity of H2A.J, and H2A.J-specific Ser-123 can be phosphorylated in response to DNA damage with potentiation of its transcriptional activity by the phospho-mimetic S123E mutation. Our work demonstrates the functional importance of H2A.J-specific residues and potential mechanisms for its function in promoting inflammatory gene expression in senescence.
Environmental DNA degradation simulation from water temperature and DNA fragment length: A meta-analysis approach
Authors: Saito Tatsuya , Doi Hideyuki
Published: October 2020

Environmental DNA (eDNA) analysis can detect aquatic organisms, including rare and endangered species, in a variety of habitats. The degradation of eDNA concentration is important to investigate their distribution and has also been experimentally evaluated. It is important to integrate these data to synthesize eDNA degradation in various environments. We collected the eDNA degradation rates and related factors, especially water temperature and fragment lengths of the measured DNA from 28 studies. Our results suggest that water temperature and fragment length are significantly related to the eDNA degradation rate. From the 95% quantile model simulation, we predicted the maximum eDNA degradation rate in various combinations of water temperature and fragment length. Predicting eDNA degradation could be important for evaluating species distribution and inducing innovation of eDNA methods, especially for rare and endangered species with lower DNA concentrations.
Reproductive history determinesErbB2locus amplification, WNT signalling and tumour phenotype in a murine breast cancer model
Authors: Ordonez Liliana D , Melchor Lorenzo , Greenow Kirsty R. , Kendrick Howard , Tornillo Giusy , Bradford James , Giles Peter , Smalley Matthew J.
Published: October 2020

Understanding the mechanisms underlying tumour heterogeneity is key to development of treatments that can target specific tumour subtypes. We have previously targeted CRE recombinase-dependent conditional deletion of the tumour suppressor genesBrca1,Brca2,p53and/orPtento basal or luminal ER− cells of the mouse mammary epithelium. We demonstrated that both the cell-of-origin and the tumour-initiating genetic lesions co-operate to influence mammary tumour phenotype. Here, we use a CRE-activated HER2 orthologue to specifically target HER2/ERBB2 oncogenic activity to basal or luminal ER− mammary epithelial cells and carry out a detailed analysis of the tumours which develop. We find that in contrast to our previous studies, basal epithelial cells are refractory to transformation by the activatedNeuKIallele, with mammary epithelial tumour formation largely confined to luminal ER− cells. Histologically, the majority of tumours that developed were classified as either adenocarcinomas of no special type or metaplastic adenosquamous tumours. Remarkably, the former were more strongly associated with virgin animals and were typically characterised by amplification of theNeuNT/ErbB2locus and activation of non-canonical WNT signalling. In contrast, tumours characterised by squamous metaplasia were associated with animals that had been through at least one pregnancy and typically had lower levels ofNeuNT/ErbB2locus amplification but had activated canonical WNT signalling. Squamous changes in these tumours were associated with activation of the Epidermal Differentiation Cluster. Thus, in this model of HER2 breast cancer, cell-of-origin, reproductive history,NeuNT/ErbB2locus amplification, and the activation of specific branches of the WNT signalling pathway all interact to drive inter-tumour heterogeneity.
Optimization of combustion and performance parameters by intake-charge conditions in a small-scale air-cooled hydrogen fuelled SI engine suitable for use in piston-prop aircraft
Authors: Gürbüz Habib
Published: October 2020

Purpose

Spark ignition (SI) engines are used in a wide area in the transportation industry, from road vehicles to piston-prop aircraft. On the other hand, the decrease in reserves of fossil fuels used in SI engines and the increase in greenhouse gas emissions makes the use of alternative fuels inevitable. In this paper, optimization of in-cylinder combustion and engine performance parameters by intake-charge conditions [i.e. intake-air temperature, injection timing and exhaust gas recirculation (EGR)] in a hydrogen (H2)-fueled small SI engine is performed.

Design/methodology/approach

Experimental studies were performed at a 1,600 rpm engine speed of a single-cylinder, air-cooled engine having a stroke volume of 476.5 cm3, maximum output power of 13 HP and torque of 25 Nm. The hydrogen-fueled SI engine was operated by a lean air-fuel mixture (ϕ = 0.6) under wide-open throttle (WOT) conditions.

Findings

The findings of the paper show that improvements can be achieved in in-cylinder combustion, indicated engine performance, exhaust NOx emissions with optimum intake-air temperature, the start of H2 injection and the ERG rate.

Practical Implications

It has been determined that a 32°C intake-air temperature, 395°C (bTDC) start of H2 injection, and 5%–10% EGR rates are the most suitable values for the examined hydrogen fueled SI engine.

Originality Value

Hydrogen is a usable alternative fuel for SI engines used in a wide area from road vehicles to piston-prop aircraft engines. However, a number of problems remain that limit hydrogen fueled SI engines to some extent, such as backfire, a decrease of engine power, and high NOx emissions. Therefore, it is appropriate to examine the effects of intake-charge conditions on in-cylinder combustion, engine performance, and NOx emissions parameters in a hydrogen fuelled SI engine.