bluuebunny/crossref_metadata_2025 huggingface dataset:
Preventing Falls Among Behavioral Health Patients
Authors: Ocker Stephanie Ann , Barton Sandra A. , Bollinger Norma , Leaver Cynthia A. , Harne-Britner Sarah , Heuston Melanie M.
Published: June 2020

Background:

Inpatient falls are among the most common hospital incidents reported. Fall-related injuries have significant implications for patients, staff, and organizations. Adult behavioral health inpatients are responsible for higher rates of injurious falls and challenge traditional fall prevention methods. An inpatient behavioral health unit in an acute care hospital identified an increased rate of injury from falls per 1,000 patient-days in three months; three falls resulted in major injury.

Purpose:

The purpose of this quality improvement (QI) report is to describe the redesign of a fall prevention program for adult behavioral health inpatients using evidence-based practice (EBP) and QI methods.

Methods:

Root cause analyses (RCAs) were conducted on all three fall-related major injuries. Concurrently, a literature review identified EBP recommendations for fall prevention on behavioral health units. A fall prevention action program was developed consisting of four elements: RN education to improve Morse Fall Scale scoring, individualized fall prevention patient plans, revised staff workflow, and improved fall prevention communication.

Results:

There were no fall-related injuries for six months and no fall-related major injuries for 12 months following implementation of the fall prevention program. Overall, this reduction in fall-related major injuries was sustained over a 21-month period.

Conclusion:

An interprofessional team approach using EBP and RCA is effective in redesigning and implementing a fall prevention program for the adult inpatient behavioral health population.
Acceptance Was the Key
Authors: Marmion Andy
Published: June 2020

A psychiatric nurse confronts the stigma of his own depression.
Matrix Metalloproteinase 11 as a Novel Tumor Promoter and Diagnostic and Prognostic Biomarker for Pancreatic Ductal Adenocarcinoma
Authors: Zhang Xu , Lu Jun , Zhou Li , You Lei , Liang Zhiyong , Guo Junchao , Zhao Yupei
Published: June 2020

Objectives

Matrix metalloproteinase 11 (MMP-11) was found to be implicated in tumorigenesis in cancers. However, the significance of MMP-11 in pancreatic ductal adenocarcinoma (PDAC) is unclear.

Methods

In the study, we detected malignant biological behaviors of pancreatic cancer after downregulation of MMP-11. Furthermore, we explored the possible mechanism, and the diagnostic value of serum MMP-11 level was analyzed in 116 patients with pathologically confirmed PDAC. In addition, we explored their prognostic value in PDAC.

Results

We observed that MMP-11 could be expressed and activated in the cytoplasm of PDAC cells. Immunohistochemistry staining of PDAC tissues showed that MMP-11 was highly expressed in cancerous ductal epithelium instead of cancer stroma. We found that downregulation of MMP-11 inhibited proliferation of PDAC cell lines. The expression levels of cyclin-dependent kinase 4 and cyclin D1 were downregulated after MMP-11 knockdown. As for its clinical value, the serum level of MMP-11 was shown to be a potent promising diagnostic marker for PDAC.

Conclusions

Matrix metalloproteinase 11 may act as a tumor promoter, playing a positive role in PDAC development. Serum MMP-11 also has great potential to be a promising diagnostic marker for PDAC.
Professional Development Associate
Authors: Russell Jillian A. , Dickerson Pamela S.
Published: June 2020

Data from a 2017 survey of the Association for Nursing Professional Development members informed the development of resources to support the role of the professional development associate. Competency-based educational programming, a position description and evaluation templates, and other professional development resources were developed in response to this need. A follow-up survey in 2019 validated the need for continued support of this vital role in professional development departments.
Reinvigorating Evidence-Based Practice
Authors: Ydrogo Cynthia , Magnan Morris , Fedoronko Kathleen
Published: June 2020

Nurses’ capabilities for evidence-based practice (EBP) cannot be presumed. Even in institutions with longstanding commitment to promoting the use of EBP, nurses may not have the EBP knowledge and skills needed to support clinical decision-making. This article describes a multifaceted approach to (a) renewing a spirit of inquiry about EBP and research and (b) strengthening nurses’ EBP capabilities at a comprehensive cancer center.
Hydrogen Gas Alleviates Sepsis-Induced Brain Injury by Improving Mitochondrial Biogenesis Through the Activation of PGC-α in Mice
Authors: Xie Keliang , Wang Yaoqi , Yin Lijun , Wang Yuzun , Chen Hongguang , Mao Xing , Wang Guolin
Published: June 2020

Sepsis-associated encephalopathy (SAE) affects approximately one-third of septic patients, and there is a lack of effective therapeutics for SAE. Hydrogen gas is a new medical gas that exerts anti-inflammation, antioxidation, and anti-apoptotic effects and can effectively protect septic mice. Mitochondrial dysfunction, which can be improved by mitochondrial biogenesis, is a type of molecular pathology in sepsis. Peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α), which can be inhibited by SR-18292, is the key regulatory factor of mitochondrial biogenesis. Therefore, we investigated the effects of hydrogen gas on mitochondrial function and mitochondrial biogenesis in mice with SAE and the related regulatory mechanisms. Cecal ligation and puncture was used to induce sepsis in mice. The mice with hydrogen gas therapy were exposed to 2% H2 inhalation for 1 h beginning at both 1 and 6 h after operation, and mice were also injected with a PGC-1α inhibitor, SR-18292. We recorded the 7-day survival rates of the mice and detected their cognitive function using a Y-maze test. The Nissl bodies in the CA1 region of hippocampus were observed by Nissl staining, and the apoptotic cells were observed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay staining. The mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) level, and mitochondrial respiratory chain complexes I and II were analyzed using commercial kits. The mitochondrial morphology was observed by transmission electron microscopy. The expression levels of PGC-1α, nuclear respiratory factor 2 (NRF2), and mitochondrial transcription factor A (Tfam) were detected by Western blot analysis. The present study showed that hydrogen gas therapy increased the 7-day survival rate, improved cognitive function, increased the mitochondrial function (MMP, ATP level, complex I activity) and expression of mitochondrial biogenesis parameters (PGC-1α, NRF2, Tfam). However, the injection of SR-18292 (a PGC-1α inhibitor) decreased mitochondrial function, PGC-1α activation, and expression of NRF2 and Tfam. Therefore, these results indicate that hydrogen gas alleviates sepsis-induced brain injury in mice by improving mitochondrial biogenesis through the activation of PGC-1α.
Temporal Dysregulation of the Angiopoietin-2/-1 Ratio After Trauma and Associations With Injury Characteristics and Outcomes
Authors: Uhlich Rindi M. , Richter Robert P. , Hu Parker J. , Kirkman Alyssa A. , Ashtekar Amit R. , Zheng Lei , Walker Shannon C. , Reynolds Lindy M. , Griffin Russell L. , Jansen Jan O. , Kerby Jeffrey D. , Richter Jillian R.
Published: June 2020

Traumatic injury and hemorrhagic shock result in endothelial cell activation and vascular dysfunction that, if not corrected, can propagate multiorgan failure. Angiopoietin-1 and angiopoietin-2 are important regulators of endothelial cell function, and the ratio of plasma angiopoietin-2-to-1 is a useful indicator of overall vascular health. We therefore characterized plasma angiopoietin-2/-1 ratios over time after trauma in adults in an effort to gain insight into the pathophysiology that may drive post-traumatic vasculopathy and organ injury. We performed a single-center prospective observational study to measure plasma angiopoietin-1 and -2 levels and determine angiopoietin-2/-1 ratios in adult trauma patients upon hospital arrival and after 12, 24, and 48 h. Compared with levels in healthy adults, angiopoietin-1 levels were significantly elevated at hospital arrival, and angiopoietin-2 levels were significantly elevated at 12, 24, and 48 h. These kinetics translated in angiopoietin-2/-1 ratios that were significantly greater than controls at 24 and 48 h. After regression analysis, elevated angiopoietin-2 levels were independently associated with blunt injuries at admission, with coagulopathy at admission and 12 h, and with hemorrhagic shock at 24 and 48 h. Significant correlations were observed between both angiopoietins and 24-h transfusion requirements. Angiopoietin-2/-1 ratios correlated with mechanical ventilation duration and intensive care unit and hospital lengths of stay. In this study, we demonstrate novel temporal associations between angiopoietin dysregulation and blunt injuries, acute coagulopathy, and hemorrhagic shock. Moreover, our findings highlight the presence of endothelial activation following traumatic insults in adults that may contribute to worse clinical outcomes.
Human Lungs Airway Epithelium Upregulate MicroRNA-17 and MicroRNA-548b in Response to Cold Ischemia and Ex Vivo Reperfusion
Authors: Elgharably Haytham , Okamoto Toshihiro , Ayyat Kamal S. , Niikawa Hiromichi , Meade Sirena , Farver Carol , Chan E. Ricky , Aldred Micheala A. , McCurry Kenneth R.
Published: June 2020

Background.

Lung ischemia-reperfusion injury after transplantation is associated with worse clinical outcomes. MicroRNA (miR) are critical regulators of gene expression that could provide potential targets for novel gene therapy. Herein, we aim to examine the feasibility of using the ex vivo lung perfusion (EVLP) platform to examine the changes in miR expression in human lungs in response to cold ischemia and ex vivo reperfusion (CI/EVR).

Methods.

Twenty-four human lungs were perfused in cellular EVLP system for 2 h, and tissue samples were obtained before and after EVLP as well as from control donors. MicroRNA expression profiling of the lung tissue was performed using next-generation sequencing and downstream predicted target genes were examined. In situ hybridization assay of the validated miR was used to identify the expressing cell type.

Results.

After 2 h of EVLP, cytokines production was significantly increased (IL-1β, IL-6, IL-8, IL-10, and TNF-α). MicroRNA sequencing identified a significant change in the expression of a total of 21 miR after CI and 47 miR after EVR. Validation using quantitative polymerase chain reaction showed significant upregulation of miR-17 and miR548b after CI/EVR. Downstream analysis identified abundant inflammatory and immunologic targets for miR-17 and miR-548b that are known mediators of lung injury. In situ hybridization assays detected positive signals of the 2 miR expression in alveolar epithelial cells.

Conclusions.

This study demonstrates the feasibility of using the EVLP platform to study miR signature in human lungs in response to CI/EVR. We found that miR-17 and miR-548b were upregulated in alveolar epithelial cells after CI/EVR, which merit further exploration.
The Knowledge, attitude and practices about bio-medical waste management system in a tertiary care 60 bedded hospital in Rajasthan, India
Authors: Verma Virender , Soni Priya , Kalhan Meenakshi , Nanda Sanjiv , Kumar Anjani , Nandan Vivek
Published: June 2020

Background and Purpose

From antiquity, the healthcare facilities have treated sick people but there was little awareness about the fact that hospitals generate a lot of hazardous bio-medical waste, which had been disposed without proper guidelines. Lately, it has been a proven thing that bio-medical-waste is a potential hazard for heath-personals, and environment. Therefore, it must be disposed in a proper manner.

Objectives

This was an observational study carried out at one of the tertiary care hospitals in Rajgarh city about the knowledge, attitude and practices of the hospital staff about the bio-medical waste management.

Material and method

An observational (cross-sectional) study using questionnaires was carried out at one of the non-NABH accredited tertiary care hospitals of Rajgarh City in Rajasthan (India).

Results

More than 70% staff (except housekeeping) had good ideas about waste categories, segregation and color coding except in radioactive waste. The house keeping staff did well in 3 categories (Linen, sharps and glasses). Most of the employees has clarity about BMW except the housekeeping staff which did well on most of parameters except barcoding, pretreatment of anatomical/ biotechnology waste, knowledge about STP plant (Sewage treatment plant), Hazmat and signage. On actual hospital rounds we found that the hazmat practices were in a poor shape. Most of staff was aware occupational hazards except housekeeping staff.

Conclusion

A written policy, induction training of healthcare workers, constant and repetitive workshops, and motivation are important human factors to implement the biomedical waste practices in a small-scale healthcare organization. Risk-stratification, understanding of health hazards and how to activate hazmat protocols are important things which are to be brought into practice.
Innocent until proven guilty: Privacy-preserving search over a central CODIS criminal database from the field
Authors: Blindenbach Jacob A. , Jagadeesh Karthik A. , Bejerano Gill , Wu David J.
Published: June 2020

The presumption of innocence (i.e., the principle that one is considered innocent until proven guilty) is a cornerstone of the criminal justice system in many countries, including the United States. DNA analysis is an important tool for criminal investigations1. In the U.S. alone, it has already aided in over half a million investigations using the Combined DNA Index System (CODIS) and associated DNA databases2. CODIS includes DNA profiles of crime scene forensic samples, convicted offenders, missing persons and more. The CODIS framework is currently used by over 50 other countries3including much of Europe, Canada, China and more. During investigations, DNA samples can be collected from multiple individuals who may have had access to, or were found near a crime scene, in the hope of finding a single criminal match4. Controversially, CODIS samples are sometimes retained from adults and juveniles despitenotyielding any database match4–6. Here we introduce a cryptographic algorithm that finds any and all matches of a person’s DNA profile against a CODIS databasewithoutrevealing anything about the person’s profile to the database provider. With our protocol, matches are immediately identified as before; however, individuals who donotmatch anything in the database retain their full privacy. Our novel algorithm runs in 40 seconds on a CODIS database of 1,000,000 entries, enabling its use to privately screen potentially-innocent suspects even in the field.
Mass-spectrometry-based near-complete draft of theSaccharomyces cerevisiae proteome
Authors: Gao Yuan , Ping Lingyan , Duong Duc , Zhang Chengpu , Dammer Eric B. , Li Yanchang , Chen Peiru , Chang Lei , Gao Huiying , Wu Junzhu , Xu Ping
Published: June 2020

Proteomics approaches designed to catalogue all open reading frames (ORFs) under a defined set of growth conditions of an organism have flourished in recent years. However, no proteome has been sequenced completely so far. Here we generate the largest yeast proteome dataset, including 5610 identified proteins using a strategy based on optimized sample preparation and high-resolution mass spectrometry. Among the 5610 identified proteins, 94.1% are core proteins, which achieves near complete coverage of the yeast ORFs. Comprehensive analysis of missing proteins in our dataset indicate that the MS-based proteome coverage has reached the ceiling. A review of protein abundance shows that our proteome encompasses a uniquely broad dynamic range. Additionally, these values highly correlate with mRNA abundance, implying a high level of accuracy, sensitivity and precision. We present examples of how the data could be used, including re-annotating gene localization, providing expression evidence of pseudogenes. Our near complete yeast proteome dataset will be a useful and important resource for further systematic studies.
3D Visualization of Macromolecule Synthesis
Authors: Duerr Timothy J. , Comellas Ester , Jeon Eun Kyung , Farkas Johanna E. , Joetzjer Marylou , Garnier Julien , Shefelbine Sandra J. , Monaghan James R.
Published: June 2020

Measuring nascent macromolecular synthesisin vivois key to understanding how cells and tissues progress through development and respond to external cues. Here, we performin vivoinjection of alkyne- or azide-modified analogs of thymidine, uridine, methionine, and glucosamine to label nascent synthesis of DNA, RNA, protein, and glycosylation. Three-dimensional volumetric imaging of nascent macromolecule synthesis was performed in axolotl salamander tissue using whole mount click chemistry-based fluorescent staining followed by light sheet fluorescent microscopy. We also developed an image processing pipeline for segmentation and classification of morphological regions of interest and individual cells, and we apply this pipeline to the regenerating humerus. We demonstrate our approach is sensitive to biological perturbations by measuring changes in DNA synthesis after limb denervation. This method provides a powerful means to quantitatively interrogate macromolecule synthesis in heterogenous tissues at the organ, cellular, and molecular levels of organization.
Distributions of LRS in varying environments
Authors: Tuljapurkar Shripad , Zuo Wenyun , Coulson Tim , Horvitz Carol , Gaillard Jean-Michel
Published: June 2020

Studies of lifetime reproductive success (LRS) have shown that important random events can be in ecology and evolution. Randomness should be amplified in stochastic environments, and here we show here we show this to be the case by computing the complete distribution of LRS when vital rates are Markovian can be readily computed by building on our recent paper (Tuljapurkar et al. 2020). These results complement the work of van Daalen and Caswell (2020) on moments of LRS. We use empirical studies of Roe deer,Capreolus capreolus, to show that environments at birth have strong effects on future performance, and that analyses of the LRS in stochastic environments are a valuable element of studies of the consequences of climate change.
Positive interactions are common among culturable bacteria
Authors: Kehe Jared , Ortiz Anthony , Kulesa Anthony , Gore Jeff , Blainey Paul C. , Friedman Jonathan
Published: June 2020

Interspecies interactions shape the structure and function of microbial communities. In particular, positive, growth-promoting interactions can significantly affect the diversity and productivity of natural and engineered communities. However, the prevalence of positive interactions and the conditions in which they occur are not well understood. To address this knowledge gap, we used kChip, an ultra-high throughput coculture platform, to measure 180,408 interactions among 20 soil bacteria across 40 carbon environments. We find that positive interactions, often described to be rare, occur commonly, primarily as parasitisms between strains that differ in their carbon consumption profiles. Notably, non-growing strains are almost always promoted by strongly growing strains (85%), suggesting a simple positive interaction-mediated approach for cultivation, microbiome engineering, and microbial consortium design.

One Sentence Summary

Experimental measurement of >150,000 bacterial cocultures reveals that growth-promoting interactions occur commonly and depend on differences in nutrient consumption preferences.
Early cardiac inflammation as a driver of murine model of Arrhythmogenic Cardiomyopathy
Authors: Ng K.E. , Delaney P.J. , Thenet D. , Murtough S. , Webb C.M. , Tsisanova E. , Walker S.L.M , Westaby J.D. , Pennington D.J , Pink R. , Kelsell D.P. , Tinker A.
Published: June 2020

The study of a desmoglein 2 murine model of arrhythmogenic cardiomyopathy revealed cardiac inflammation as a key early event leading to fibrosis. Arrhythmogenic Cardiomyopathy (AC) is an inherited heart muscle disorder leading to ventricular arrhythmias and heart failure due to abnormalities in the cardiac desmosome. We examined how loss of desmoglein 2 (Dsg2) in the young murine heart leads to development of AC. Cardiomyocyte apoptosis was an early cellular phenotype and RNA-Seq analysis revealed early activation of inflammatory-associated pathways inDsg2null (Dsg2−/−) hearts at postnatal day 14 (Two weeks) that were absent in the fibrotic heart of adult mice (Ten weeks). This included upregulation of iRhom2/ADAM17 and its associated pro-inflammatory cytokines and receptors such as TNFα, IL6R and IL-6. Furthermore, genes linked to specific macrophage populations were upregulated. This suggests cardiomyocyte stress triggers an early immune response to clear apoptotic cells allowing tissue remodelling later on in the fibrotic heart. Our analysis at different disease stages implicate inflammation related to loss of desmoglein 2 as a major mechanism for disease progression.
Influenza Vaccination and COVID19 Mortality in the USA
Authors: Zanettini Claudio , Omar Mohamed , Dinalankara Wikum , Imada Eddie Luidy , Colantuoni Elizabeth , Parmigiani Giovanni , Marchionni Luigi
Published: June 2020

COVID-19 mortality rate is higher in the elderly and in those with preexisting chronic medical conditions. The elderly also suffer from increased morbidity and mortality from seasonal influenza infection, and thus annual influenza vaccination is recommended for them.

In this study, we explore a possible area-level association between influenza vaccination coverage in people aged 65 years and older and the number of deaths from COVID-19. To this end, we used COVID-19 data until June 10, 2020 together with population health data for the United States at the county level. We fit quasi-Poisson regression models using influenza vaccination coverage in the elderly population as the independent variable and the number of deaths from COVID-19 as the outcome variable. We adjusted for a wide array of potential confounding variables using both county-level generalized propensity scores for influenza vaccination rates, as well as direct adjustment.

Our results suggest that influenza vaccination coverage in the elderly population is negatively associated with mortality from COVID-19. This finding is robust to using different analysis periods, different thresholds for inclusion of counties, and a variety of methodologies for confounding adjustment.

In conclusion, our results suggest a potential protective effect of the influenza vaccine on COVID-19 mortality in the elderly population. The significant public health implications of this possibility point to an urgent need for studying the relationship between influenza vaccination and COVID-19 mortality at the individual level, to investigate both the epidemiology and any underlying biological mechanism.
Elevated levels of PM2.5 in crowded Subways of Cities with High COVID-19 related Mortality
Authors: Baron Yves Muscat
Published: June 2020

BACKGROUND

Recent literature indicates that the pollutant, particulate matter PM2.5, may have an impact on COVID-19 related mortality. COVID-19 has been found adherent to PM2.5 and may be involved in the transmission and the exacerbation of COVID-19 infection, possibly due to PM2.5’s adverse influence on respiratory immunity. The PM2.5 levels in underground subways have been found up to 90 times higher than the surface levels. Moreover, the commuter congestion in the presence of such high levels of PM2.5 further encouraged COVID-19 human to human transmission.

METHOD

The levels of PM2.5 were retrieved from literature assessing particulate matter PM2.5 measured on subway platforms in two groups of cities. These cities were differentiated by the COVID-19 population percentage mortality rate (0.007% vs 0.09% (p<0.0004) the city’s population, more than a 10-fold difference. Data regarding the number of stations, length of the networks (km) and the annual ridership were also obtained from literature related to underground commuting.

RESULTS

The population percentage mortality related to COVID-19 infection correlated significantly for both minimum (p<0.01) and maximum (p<0.00001) levels of PM2.5. The cities’ subways with low COVID-19 mortality had minimum platform PM2.5 levels of 27.4 (SD+/-17.2µg/m3) compared to 63.4µg/m3 (SD+/-10.8µg/m3) in cities with high COVID-19 associated mortality (p<0.01). Subway maximum levels of PM2.5 in cities with low COVID-19 mortality was 53.4µg/m3 (SD+/- 21.8µg/m3) while that of underground networks with high COVID-19 mortality had maximum platform PM2.5 levels of 172.1µg/m3 (SD+/-98µg/m3) (p<0.001). The cities with higher COVID-19 mortality had longer networks 230km (SD+/-111km) versus 119km (SD+/-99km) (p<0.03) and more stations 191 (SD+/-109) versus 102 (SD+/-94) (p<0.047). Although the annual ridership in the cities with the high COVID-19 mortality was higher (1034×106 vs 751×106) this did not achieve statistical significance. The maximum PM2.5 correlated with the number of stations (p<0.045) and the length of the networks (p< 0.044). The minimum PM2.5 did not achieve similar significant correlations to subway variables. Ridership significantly correlated with number of stations (p<0.01) and the length of the network (p<0.02).

CONCLUSION

Underground networks may have inherent characteristics accelerating spread of COVID-19 infection and consequent mortality. The highly elevated levels of PM2.5 in overcrowded subways with extensive reach may have acted as a co-factor to disseminate the pandemic.
A Multi-Task Pipeline with Specialized Streams for Classification and Segmentation of Infection Manifestations in COVID-19 Scans
Authors: EL-Bana Shimaa , Al-Kabbany Ahmad , Sharkas Maha
Published: June 2020

We are concerned with the challenge of coronavirus disease (COVID-19) detection in chest X-ray and Computed Tomography (CT) scans, and the classification and segmentation of related infection manifestations. Even though it is arguably not an established diagnostic tool, using machine learning-based analysis of COVID-19 medical scans has shown the potential to provide a preliminary digital second opinion. This can help in managing the current pandemic, and thus has been attracting significant research attention. In this research, we propose a multi-task pipeline that takes advantage of the growing advances in deep neural network models. In the first stage, we fine-tuned an Inception-v3 deep model for COVID-19 recognition using multi-modal learning, i.e., using X-ray and CT scans. In addition to outperforming other deep models on the same task in the recent literature, with an attained accuracy of 99.4%, we also present comparative analysis for multi-modal learning against learning from X-ray scans alone. The second and the third stages of the proposed pipeline complement one another in dealing with different types of infection manifestations. The former features a convolutional neural network architecture for recognizing three types of manifestations, while the latter transfers learning from another knowledge domain, namely, pulmonary nodule segmentation in CT scans, to produce binary masks for segmenting the regions corresponding to these manifestations. Our proposed pipeline also features specialized streams in which multiple deep models are trained separately to segment specific types of infection manifestations, and we show the significant impact that this framework has on various performance metrics. We evaluate the proposed models on widely adopted datasets, and we demonstrate an increase of approximately 4% and 7% for dice coefficient and mean intersection-over-union (mIoU), respectively, while achieving 60% reduction in computational time, compared to the recent literature.
Determination of Robust Regional CT Radiomics Features for COVID-19
Authors: Tamal Mahbubunnabi
Published: June 2020

Background

The lung CT images of COVID-19 patients can be characterized by three different regions – Ground Glass Opacity (GGO), consolidation and pleural effusion. GCOs have been shown to precede consolidations. Quantitative characterization of these regions using radiomics can facilitate accurate diagnosis, disease progression and response to treatment. However, according to the knowledge of the author, regional CT radiomics analysis of COVID-19 patients has not been carried out. This study aims to address these by determining the radiomics features that can characterize each of the regions separately and can distinguish the regions from each other.

Methods

44 radiomics features were generated with four quantization levels for 23 CT slice of 17 patients. Two approaches were the implemented to determine the features that can differentiate between lung regions – 1) Z-score and correlation heatmaps and 2) one way ANOVA for finding statistically significantly difference (p<0.05) between the regions. Radiomics features that show agreement for all cases (Z-score, correlation and statistical significant test) were selected as suitable features. The features were then tested on 52 CT images.

Results

10 radiomics features were found to be the most suitable among 44 features. When applied on the test images, they can differentiate between GCO, consolidation and pleural effusion successfully and the difference provided by these 10 features between three lung regions are statistically significant.

Conclusion

The ten robust radiomics features can be useful in extracting quantitative data from CT lung images to characterize the disease in the patient, which in turn can help in more accurate diagnosis, staging the severity of the disease and allow the clinician to plan for more successful personalized treatment for COVID-19 patients. They can also be used for monitoring the progression of COVID-19 and response to therapy for clinical trials.
Modelling lockdown-induced 2ndCOVID waves in France
Authors: Daunizeau Jean , Moran Rosalyn , Brochard Jules , Mattout Jérémie , Frackowiak Richard , Friston Karl
Published: June 2020

As with the Spanish Flu a century ago, authorities have responded to the current COVID-19 pandemic with extraordinary public health measures. In particular, lockdown and related social distancing policies are motivated in some countries by the need to slow virus propagation—so that the primary wave of patients suffering from severe forms of COVID infection do not exceed the capacity of intensive care units. But unlocking poses a critical issue because relaxing social distancing may, in principle, generate secondary waves. Ironically however, the dynamic repertoire of established epidemiological models that support this kind of reasoning is limited to single epidemic outbreaks. In turn, predictions regarding secondary waves are tautologically derived from imposing assumptions about changes in the so-called “effective reproduction number”. In this work, we depart from this approach and extend the LIST (Location-Infection-Symptom-Testing) model of the COVID pandemic with realistic nonlinear feedback mechanisms that under certain conditions, cause lockdown-induced secondary outbreaks. The original LIST model captures adaptive social distancing,i.e. the transient reduction of the number of person-to-person contacts (and hence the rate of virus transmission), as a societal response to salient public health risks. Here, we consider the possibility that such pruning of socio-geographical networks may also temporarily isolate subsets of local populations from the virus. Crucially however, such unreachable people will become susceptible again when adaptive social distancing relaxes and the density of contacts within socio-geographical networks increases again. Taken together, adaptive social distancing and networkunreachabilitythus close a nonlinear feedback loop that endows the LIST model with a mechanism that can generate autonomous (lockdown-induced) secondary waves. However, whether and how secondary waves arise depend upon the interaction with other nonlinear mechanisms that capture other forms of transmission heterogeneity. We apply the ensuing LIST model to numerical simulations and exhaustive analyses of regional French epidemiological data. In brief, we find evidence for this kind of nonlinear feedback mechanism in the empirical dynamics of the pandemic in France. However, rather than generating catastrophic secondary outbreaks (as is typically assumed), the model predicts that the impact of lockdown-induced variations in population susceptibility and transmission may eventually reduce to a steady-state endemic equilibrium with a low but stable infection rate.
Estimating COVID-19 under-reporting across 86 nations: implications for projections and control
Authors: Rahmandad Hazhir , Lim Tse Yang , Sterman John
Published: June 2020

COVID-19 prevalence and mortality remain uncertain. For all 86 countries with reliable testing data we estimate how asymptomatic transmission, disease acuity, hospitalization, and behavioral responses to risk shape pandemic dynamics. Estimated cumulative cases and deaths through 10 July 2020 are 10.5 and 1.47 times official reports, yielding an infection fatality rate (IFR) of 0.65%, with wide variation across nations. Despite underestimation, herd immunity remains distant. Sufficient early testing could have averted 39.7 (35.3-45.3) million cases and 218 (191-257) thousand deaths. Responses to perceived risk cause the reproduction number to settle near 1, but with very different steady-state incidence, while some nations experience endogenous rebounds. Scenarios through March 2021 show modest enhancements in responsiveness could reduce cumulative cases ≈80%, to 271 (254-412) million across these nations.

One Sentence Summary

COVID-19 under-reporting is large, varies widely across nations, and strongly conditions projected outbreak dynamics.
Characterization of a novel, low-cost, scalable ozone gas system for sterilization of N95 respirators and other COVID-19 related use cases.
Authors: Dave Nikhil , Pascavis Katie Sue , Patterson John , Kozicki Michael , Wallace David , Chowdhury Abhik , Abbaszadegan Morteza , Alum Absar , Herckes Pierre , Zhang Zhaobo , Chang Josh , Ewell Clinton , Smith Tyler , Naufel Mark
Published: June 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an elusive and highly pathogenic agent, has resulted in the ongoing COVID-19 pandemic affecting numerous populations worldwide. New studies investigating the tenacity of SARS-CoV-2 have highlighted its ability to persist on a myriad of surfaces for several days, including gowns and shoes. As a result, there is a global need for sterilization of a variety of potentially-contaminated items, ranging from clothing to personal protective equipment like face coverings. To this end, we have designed and constructed a cost-effective, scalable, and sustainable sterilization system that uses ozone gas to inactivate viral particles. We sought to determine the efficacy of the system in the sterilization of viral particles as well as its ability to sterilize N95 respirators for reuse. N95 respirators inoculated with P22 bacteriophage and sterilized in the ozone system showed a 6-log10 reduction in viral load when treated at 25 ppm for 150 minutes. Further, N95 respirators treated with five 150-minute cycles at 35 ppm for a total concentration-time product (CT) of 26,250 ppm min in the ozone system showed comparable filtration efficiency to untreated N95 respirators in a 50 to 200 nmr particulate challenge filtration test. Interestingly, the surgical N95 respirators tested showed complete inactivation of fluid resistance and degradation of the elasticity of polyisoprene straps after five cycles in the sterilization system. Taken together, these data suggest that while our ozone system may negatively affect certain protective aspects of surgical N95 respirators, it does effectively sterilize viral particles and can be utilized for a multitude of other use cases, including sterilizing polypropylene face coverings after potential SARS-CoV-2 contamination. In addition to providing long-term environmental benefits, deployment of this system during the ongoing pandemic reduces the risk of COVID-19 community transmission while conserving monetary resources otherwise spent on the continuous purchase of disposable face coverings.
Shut and re-open: the role of schools in the spread of COVID-19 in Europe
Authors: Stage Helena B. , Shingleton Joseph , Ghosh Sanmitra , Scarabel Francesca , Pellis Lorenzo , Finnie Thomas
Published: June 2020

We investigate the effect of school closure and subsequent reopening on the transmission of COVID-19, by considering Denmark, Norway, Sweden, and German states as case studies. By comparing the growth rates in daily hospitalisations or confirmed cases under different interventions, we provide evidence that school closures contribute to a reduction in the growth rate approximately 7 days after implementation. Limited school attendance, such as older students sitting exams or the partial return of younger year groups, does not appear to significantly affect community transmission. In countries where community transmission is generally low, such as Denmark or Norway, a large-scale reopening of schools while controlling or suppressing the epidemic appears feasible. However, school reopening can contribute to statistically significant increases in the growth rate in countries like Germany, where community transmission is relatively high. In all regions, a combination of low classroom occupancy and robust test-and-trace measures were in place. Our findings underscore the need for a cautious evaluation of reopening strategies.
Evaluating aerosol and splatter following dental procedures: addressing new challenges for oral healthcare and rehabilitation
Authors: Allison James R , Currie Charlotte C , Edwards David C , Bowes Charlotte , Coulter Jamie , Pickering Kimberley , Kozhevnikova Ekaterina , Durham Justin , Nile Christopher J , Jakubovics Nicholas , Rostami Nadia , Holliday Richard
Published: June 2020

Background

Dental procedures often produce aerosol and splatter which are potentially high risk for spreading pathogens such as SARS-CoV-2. The existing literature is limited.

Objective(s)

To develop a robust, reliable and valid methodology to evaluate distribution and persistence of dental aerosol and splatter, including the evaluation of clinical procedures.

Methods

Fluorescein was introduced into the irrigation reservoirs of a high-speed air-turbine, ultrasonic scaler and 3-in-1 spray and procedures performed on a mannequin in triplicate. Filter papers were placed in the immediate environment. The impact of dental suction and assistant presence were also evaluated. Samples were analysed using photographic image analysis, and spectrofluorometric analysis. Descriptive statistics were calculated and Pearson’s correlation for comparison of analytic methods.

Results

All procedures were aerosol and splatter generating. Contamination was highest closest to the source, remaining high to 1-1.5 m. Contamination was detectable at the maximum distance measured (4 m) for high-speed air-turbine with maximum relative fluorescence units (RFU) being: 46,091 at 0.5 m, 3,541 at 1.0 m, and 1,695 at 4 m. There was uneven spatial distribution with highest levels of contamination opposite the operator. Very low levels of contamination (≤0.1% of original) were detected at 30 and 60 minutes post procedure. Suction reduced contamination by 67-75% at 0.5-1.5 m. Mannequin and operator were heavily contaminated. The two analytic methods showed good correlation (r=0.930, n=244, p<0.001).

Conclusion

Dental procedures have potential to deposit aerosol and splatter at some distance from the source, being effectively cleared by 30 minutes in our setting.
High-Throughput Kinase Inhibitor Screening Reveals Roles for Aurora and Nuak Kinases in Neurite Initiation and Dendritic Branching
Authors: Blazejewski Sara M. , Bennison Sarah A. , Liu Xiaonan , Toyo-oka Kazuhito
Published: June 2020

Kinases are essential regulators of a variety of cellular signaling processes, including neurite formation – a foundational step in neurodevelopment. Aberrant axonal sprouting and failed regeneration of injured axons are associated with conditions like traumatic injury, neurodegenerative disease, and seizures. Investigating the mechanisms underlying neurite formation will allow for identification of potential therapeutics. We used a kinase inhibitor library to screen 493 kinase inhibitors and observed that 45% impacted neuritogenesis in Neuro2a (N-2a) cells. Based on the screening, we further investigated the roles of Aurora kinases A, B, and C and Nuak kinases 1 and 2. The roles of Aurora and Nuak kinases have not been thoroughly studied in the nervous system. Inhibition or overexpression of Aurora and Nuak kinases in primary cortical neurons resulted in various neuromorphological defects, with Aurora A regulating neurite initiation, Aurora B and C regulating neurite initiation and elongation, all Aurora kinases regulating arborization, and all Nuak kinases regulating neurite initiation and elongation and arborization. Our high-throughput screening and analysis of Aurora and Nuak kinases revealed their functions and may contribute to the identification of therapeutics.
A new experimental system to study meiotic recurrent non-allelic homologous recombination in budding yeast
Authors: Sedam Hailey N. C. , Argueso Juan Lucas
Published: June 2020

In humans,de novorecurrent copy number variations (CNVs) often arise during meiosis from non-allelic homologous recombination (NAHR) between low copy repeat elements (LCRs). These chromosomal rearrangements are responsible for a wide variety of genomic disorders involving duplication or deletion of dose-sensitive genes. The precise factors that steer meiotic cells toward this detrimental recombination pathway are not fully understood. To create a model for the investigation of LCR-mediated CNV mechanisms, we developed a diploid experimental system inSaccharomyces cerevisiae. We modified the right arm of chromosome V through the introduction of engineered LCRs: duplicated 5 to 35 kb segments of yeast DNA flanking single copy interstitial spacers, analogously to the meiotic NAHR substrates that exist in humans. Phenotypic markers, including a copy number reporter, were inserted within the interstitial spacer. Their segregation in the haploid meiotic progeny was used to phenotypically identity and classify recurrent CNV events. This system allowed us to measure the effects of LCR size on the frequency of meioticde novorecurrent CNV formation, and to determine the relative proportions of each of the three main NAHR classes: interhomolog, intersister, and intrachromatid. The frequency of CNV increased as the LCRs became larger, and interhomolog NAHR was overrepresented relative to the two other classes. We showed that this experimental system directly mimics the features ofde novorecurrent CNVs reported in human disease, thus it represents a promising tool for the discovery and characterization of conserved cellular factors and environmental exposures that can modulate meiotic NAHR.
Pupil dilation and the slow wave ERP reflect surprise about choice outcome resulting from intrinsic variability in decision confidence
Authors: de Gee Jan Willem , Correa Camile M.C. , Weaver Matthew , Donner Tobias H. , van Gaal Simon
Published: June 2020

Central to human and animal cognition is the ability to learn from feedback in order to optimize future rewards. Such a learning signal might be encoded and broadcasted by the brain’s arousal systems, including the noradrenergic locus coeruleus. Pupil responses and the positive slow wave component of event-related potentials reflect rapid changes in the arousal level of the brain. Here we ask whether and how these variables may reflect surprise: the mismatch between one’s expectation about being correct and the outcome of a decision, when expectations fluctuate due to internal factors (e.g., engagement). We show that during an elementary decision-task in the face of uncertainty both physiological markers of phasic arousal reflect surprise. We further show that pupil responses and slow wave ERP are unrelated to each other, and that prediction error computations depend on feedback awareness. These results further advance our understanding of the role of central arousal systems in decision-making under uncertainty.
Custom-designed, degradation-resistant messenger RNAs in yeast
Authors: Franklin Ana L. , Macfadden Andrea , Kieft Jeffrey S. , Hesselberth Jay R. , Chapman Erich G.
Published: June 2020

Structured RNA elements that protect RNA transcripts from 5’→3’ degradation are becoming useful research tools. Here we show that exonuclease-resistant RNA structures (xrRNAs) from Flaviviruses can be used to protect heterologous messenger RNAs (mRNAs) from 5’→3’ degradation in budding yeast. Installation of xrRNAs ahead of a downstream internal ribosome entry site (IRES) leads to the accumulation of partially-degraded mRNAs that are substrates for cap-independent translation of a LacZ reporter, yielding a 30-fold increase in measured β-galactosidase activity. Additionally, by monitoring the translation of dual-luciferase reporters we show that xrRNA sequences do not interfere with the progression of an elongating ribosome. Combined these data indicate that xrRNA elements can be used in creative ways to stabilize RNAs with potentially useful applications.
Significant non-existence of sequences in genomes and proteomes
Authors: Koulouras Grigorios , Frith Martin C.
Published: June 2020

Nullomers are minimal-length oligomers absent from a genome or proteome. Although research has shown that artificially synthesized nullomers have deleterious effects, there is still a lack of a strategy for the prioritisation and classification of non-occurring sequences as potentially malicious or benign. In this work, by using Markovian models with multiple-testing correction, we reveal significant absent oligomers which are statistically expected to exist. This strongly suggests that their absence is due to negative selection. We survey genomes and proteomes covering the diversity of life, and find thousands of significant absent sequences. Common significant nullomers are often mono- or dinucleotide tracts, or palindromic. Significant viral nullomers are often restriction sites, and may indicate unknown restriction motifs. Surprisingly, significant mammal genome nullomers are often present, but rare, in other mammals, suggesting that they are suppressed but not completely forbidden. Significant human nullomers are rarely present in human viruses, indicating viral mimicry of the host. More than 1/4 of human proteins are one substitution away from containing a significant nullomer. We provide a web-based, interactive database of significant nullomers across genomes and proteomes.