bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Dietary Antioxidant Quality Score and Anthropometric Measurements in Children and Adolescents: The Weight Disorders Survey of the CASPIAN-IV Study
Authors: Azizi-Soleiman Fatemeh , Khoshhali Mehri , Heidari-Beni Motahar , Qorbani Mostafa , Kelishadi Roya
Published: July 2020

Background

Limited experience exists on the relationship between anthropometric measures and dietary antioxidant intake in the pediatric age group. We aimed to investigate the association of dietary antioxidants intake and anthropometric measurement in children and adolescents.

Methods

This nationwide study was conducted in 4270 children and adolescents, aged 6–18 years. Demographic and anthropometric data were assessed. Children and adolescents were classified as underweight, healthy weight or overweight/obese based on body mass index percentiles. Dietary intake was obtained by a 168-item semi-quantitative validated food frequency questionnaire. Energy and nutrients intake was estimated using the Nutritionist IV software. Dietary antioxidant quality score (DAQS) was calculated based on the daily dietary intake of selenium, zinc, vitamin A, vitamin C and vitamin E compared with daily recommended intake.

Results

After adjustment for age, gender, living area (rural or urban), energy intake and physical activity level, DAQS was positively associated with waist circumference (WC), hip circumference and waist-to-height ratio (WHtR) in under-weight children and adolescents (B = 1.614, 1.634 and 0.01, respectively; all ps < 0.05). Increased DAQS was significantly associated with higher WC and WHtR in normal–weight children and adolescents (B = 0.536 and 0.003, respectively; all ps <0.05).

Conclusion

Dietary intakes of some antioxidants were higher in children and adolescents with excess weight. DAQS was correlated with some anthropometric measurements in under-weight and normal-weight subjects. It can provide a novel approach to assess the role of antioxidant intake on health promotion and diet-based therapies in under-weight and normal-weight children and adolescents
VII Shakespeare
Authors: Young Jennifer , Smith Peter J , Parsons Elinor , Tarantino Elisabetta , Stelzer Emanuel , Bell Shirley , Haworth Ben , Lim Vanessa , O’Brien Sheilagh Ilona , Wilkinson Kate
Published: July 2020

This chapter has four sections: 1. Editions and Textual Studies; 2. Shakespeare in the Theatre; 3. Shakespeare on Screen; 4. Criticism. Section 1 is by Jennifer Young; section 2 is by Peter J. Smith; section 3 is by Elinor Parsons; section 4(a) is by Elisabetta Tarantino; section 4(b) is by Emanuel Stelzer; section 4(c) is by Shirley Bell; section 4(d) is by Ben Haworth; section 4(e) is by Vanessa Lim; section 4(f) is by Sheilagh Ilona O’Brien; section 4(g) is by Kate Wilkinson.
Passing the Chief Nursing Officer Baton: The Importance of Succession Planning and Transformational Leadership
Authors: Burke Debra , Erickson Jeanette Ives
Published: July 2020

In today's dynamic healthcare environment, it is more important than ever that the chief nursing officer (CNO) possesses transformational leadership skills. This includes the cultivation of leaders whom the CNO can partner with to advance strategic priorities that benefit patients, families, clinical nurses, and others within a strong, supportive practice environment. A collaborative partnership not only ensures the advancement of an agenda for change but also enhances communication and visibility and provides an opportunity for development of key individuals on the executive team. By supporting partnerships, the CNO has the opportunity to keep talented leaders in the pipeline and to identify those who should be a part of the succession planning process. This is a critically important concept that can lead to a smooth leadership transition.
Building Teams and Trust
Authors: Thrall Terese Hudson
Published: July 2020

This year, Ann Marie T. Brooks, PhD, MBA, RN, FAAN, FACHE, FNAP, President at Mount Carmel College of Nursing, Columbus, Ohio, received the American Organization for Nursing Leadership's (AONL's) prestigious Lifetime Achievement Award, which honors an AONL member recognized by the nursing community as a significant leader in the nursing profession and who has served AONL in an important leadership capacity. Brooks served as president of the AONL board of directors and previously received AONL's Mentor Award. In her career, she held a series of executive nurse positions at universities, academic health centers, and community hospitals, such as dean at the Catholic University of America and chief nurse executive at Strong Memorial Hospital, Rochester, New York.

Dr Brooks has extensive global nursing leadership experience including serving as chief nursing officer at King Faisal Hospital & Research Centre in Riyadh, Saudi Arabia. Her experience as a Magnet® appraiser for the past 18 years keeps her current with how nurse leaders and clinical nurses develop and embed leading practices in nursing and healthcare. To learn more about her insights and hopes for nurse leaders, AONL Managing Editor Terese Hudson Thrall posed these questions.
Creating Microclimates of Change
Authors: Werlau Timothy , Soares-Sardinha Sharmila , Overman Angela S. , Chutz Jennifer , Emory Jennifer , Jones Carla M. , Lee Gretchen , Smith-Miller Cheryl A.
Published: July 2020

OBJECTIVES

Study objectives were to: 1) explore how nursing care quality data (NCQD) was understood and interpreted; and 2) identify, compare, and contrast individual and group responses.

BACKGROUND

Little evidence exists on how to best disseminate NCQD information. This study explores the outcomes of implementing an NCQD and human-interest information slide show across an inpatient surgery nursing service line using electronic screens.

METHODS

Methods included semistructured interviews, qualitative analysis, and diagramming.

RESULTS

The human-interest content most often attracted viewers' attention, but they were also exposed to NCQD. Interpretations and understandings differed among groups and between individuals. Among staff members, the human-interest content facilitated team-building, whereas NCQD provided meaningful recognition. Nursing care quality data evidenced the efforts that were being made to improve and provide excellent patient care.

CONCLUSIONS

Using innovative dissemination methods can enhance understanding of NCQD among clinical providers. Creating microclimates of change and innovation within complex healthcare environments can benefit staff members and patients.
Empowering Nurses
Authors: Card Elizabeth B. , Wells Nancy , Abbu Stephanie N. , Myers Janet M. , Denton Traci D. , Dubree Marilyn
Published: July 2020

An internal peer-reviewed journal was created to promote high-quality nursing practice, improve patient outcomes, and inspire nurses at an academic medical center. The goal of the journal was to increase nurses' utilization of evidence-based practice (EBP). The publication provides a platform that facilitates the dissemination of nursing research and supports the implementation of EBP across the organization.
Confirmed central olfactory system lesions on brain MRI in COVID-19 patients with anosmia: a case-series
Authors: Girardeau Yannick , Gallois Yoan , De Bonnecaze Guillaume , Escudé Bernard , Lafont Clarisse , Chattelier Gilles , Marx Mathieu
Published: July 2020

Objective

Anosmia has been listed as a key-symptom associated with the COVID-19 infection. Because it often occurs without any sign of rhinitis, lesions of the central olfactory system have been suspected. To date, however, there is no evidence that anosmia caused by SARS-CoV2 could be the result of brain damage.

Methods

We conducted a case-series on 10 consecutive COVID-19 patients who reported anosmia. Each patient prospectively underwent a validated olfactory test (Sniffin’ Sticks test) and a brain MRI. Results Hypersignal intensity lesions of the central olfactory system were found in 3 subjects on 3D T2 FLAIR and 2D T2 High Resolution images with a lesion involving the olfactory bulbs and/or the orbitofrontal cortex. These 3 subjects showed a severe and persistent loss of smell on the olfactory test. Mucosal hyperplasia of the upper nasal cavities was found in two other subjects with significant smell disorders. There was no MRI anomaly in two subjects with good smell restoration.

Conclusions

Anomalies of the central olfactory system could be responsible for anosmia in patients with COVID-19 infection. Further studies are needed to assess the impact on long-term functional prognosis of these lesions.

Key Result

Central anomalies of the olfactory bulb and cortex could be responsible for anosmia in COVID-19 infection
The risk of severe COVID-19: hospital and ICU admission rates in Norway
Authors: Munkvik Morten , Alsnes Ingvild Vatten , Vatten Lars
Published: July 2020

Background

Epidemiological studies of COVID-19 with population based information may add to the knowledge needed to prioritise resources and advice on how restrictive measures should be targeted. This study provides admission rates to hospitals and intensive care units (ICU) in Norway, aiming to better understand the risk of severe COVID-19 infection.

Methods

Data from official reports from The Norwegian Institute of Public Health (NIPH) and the Norwegian Directorate of Health were used to calculate admission rates to hospitals and to ICU per 100 000 inhabitants. We compared rates of hospitalisation between the four health regions and provide separate rates for Oslo. We also assessed national admissions to ICU stratified by age.

Results

The admission rate in the south-eastern region was 3.1 per 100 000, and the rate for Oslo was 5.8. Compared to the western region (reference), the Oslo rate was 4.0 times (confidence interval (CI) 3.0-5.5) higher. In Norway as a whole, the rate of ICU admissions was 3.9 per 100 000, and in the age groups 60-69 and 70-79, ICU rates were 10.3 and 11.5, respectively. These rates were 9.5 (CI 6.3-14.3) and 10.6 (CI 6.9-16.2) times higher compared to people younger than 50 years.

Conclusion

Hospital admissions due to Covid-19 are much higher in Oslo than anywhere else in Norway, and in the country as a whole, ICU admissions are highest among people 60-79 years of age. These results and more detailed data could provide better advice on how restrictions can be safely lessened.
Outcomes of Advanced Malignant Melanoma in a South African Public Health Sector Cohort: The Urgent Need for Effective Therapy
Authors: Molefi Thulo , Med Cert
Published: July 2020

Background

Immunotherapy and molecularly targeted therapy have revolutionised the treatment of malignant melanoma, however for South Africa’s public health sector patient population, these treatment modalities are far out of reach and chemotherapy remains the only treatment option.

Aim

To evaluate the outcomes of advanced melanoma and determine the need for therapies other than conventional chemotherapy in South Africa’s public health sector.

Setting

The Department of Medical Oncology, Steve Biko Academic hospital (SBAH), Pretoria, South Africa.

Methods

Files of patients with advanced malignant melanoma managed at SBAH, from 01 January 2009 to 31 December 2019 were retrospectively reviewed.

Results

One hundred files meeting the inclusion criteria were analysed, 24 with regional (stage III) and 76 with metastatic (stage IV) disease. 23 (96%) patients with regional disease didn’t receive adjuvant therapy and had a median time to progression (mTTP) of 12 months (95%CI; 8.9-15.0). Within the metastatic melanoma cohort, 34 (79.1%) patients received chemotherapy and had a median overall survival (mOS) of 5 months (95% CI; 4.3-5.6), while patients that didn’t receive chemotherapy had a mOS of 2 months (95% CI; 0.8-3.1) (p=0.213).

Conclusion

These results reaffirm the impotent effects of chemotherapy in treating malignant melanoma and it is imperative that South Africa’s public health sector expands its armamentarium against this lethal disease.
Using Machine-Learning for Prediction of the Response to Cardiac Resynchronization Therapy: the SMART-AV Study
Authors: Howell Stacey J. , Stivland Tim , Stein Kenneth , Ellenbogen Kenneth A. , Tereshchenko Larisa G.
Published: July 2020

Background

There is a controversy whether the response of both sexes to cardiac resynchronization therapy (CRT) is similar. Optimal CRT delivery requires procedure planning.

Objective

To apply machine learning (ML) to develop a prediction model for CRT response.

Methods

Participants from the SmartDelay Determined AV Optimization (SMART-AV) trial (n=741; age, 66 ±11 yrs; 33% female; 100% NYHA III-IV; 100% EF≤35%) were randomly split into training & testing (80%; n=593), and validation (20%; n=148) samples. The entropy balancing procedure was used to match for the means of 30 covariates in male and female groups. Baseline clinical, ECG, echocardiographic and biomarker characteristics, and left ventricular (LV) lead position (43 variables) were included in 6 ML models (random forests, convolutional neural network, lasso, adaptive lasso, plugin lasso, elastic net, ridge, and logistic regression). A composite of freedom from death and heart failure hospitalization and a >15% reduction in LV end-systolic volume index at 6-months post-CRT was the endpoint.

Results

The primary endpoint was met by 337 patients (45.5%). Weighting resulted in a perfect balance of means of covariates in men and women. After reweighting, CRT response for women versus men was similar (OR 1.53; 95%CI 0.88-2.65; P=0.131). The adaptive lasso model was more accurate than class I ACC/AHA guidelines criteria (AUC 0.759; 95%CI 0.678-0.840 versus 0.639; 95%CI 0.554-0.722;P<0.0001), well-calibrated, and parsimonious (19 predictors; nearly half are potentially modifiable).

Conclusions

After balancing for covariates, both sexes similarly benefit from CRT. ML predicts short-term CRT response and thus may help with CRT procedure planning.
The impact of climate temperature on counts, recovery, and death rates due to SARS-CoV-2 in South Africa
Authors: Chetty Naven , Adeleye Bamise , Ilori Abiola Olawale
Published: July 2020

The impact of climate temperature on the counts (number of positive COVID-19 cases reported), recovery, and death rates of COVID-19 cases in South Africa’s nine provinces was investigated. The data for confirmed cases of COVID-19 were collected for March 25 and June 30, 2020 (14 weeks) from South Africa’s Government COVID-19 online resource, while the daily provincial climate temperatures were collected from the website of the South African Weather Service. Our result indicates that a higher or lower climate temperature does not prevent or delay the spread and death rates but shows significant positive impacts on the recovery rates of COVID-19 patients. Thus, it indicates that the climate temperature is unlikely to impose a strict limit on the spread of COVID-19. There is no correlation between the cases and death rates, an indicator that no particular temperature range is closely associated with a faster or slower death rate of COVID-19 patients. As evidence from our study, a warm climate temperature can only increase the recovery rate of COVID-19 patients, ultimately impacting the death and active case rates and freeing up resources quicker to enable health facilities to deal with those patients’ climbing rates who need treatment.
Probability of aerosol transmission of SARS-CoV-2
Authors: Smith Scott H. , Somsen G. Aernout , van Rijn Cees , Kooij Stefan , van der Hoek Lia , Bem Reinout A. , Bonn Daniel
Published: July 2020

Transmission of SARS-CoV-2 leading to COVID-19 occurs through exhaled respiratory droplets from infected humans. Currently, however, there is much controversy over whether respiratory aerosol microdroplets play an important role as a route of transmission. By measuring and modeling the dynamics of exhaled respiratory droplets we can assess the relative contribution of aerosols in the spreading of SARS-CoV-2. We measure size distribution, total numbers and volumes of respiratory droplets, including aerosols, by speaking and coughing from healthy subjects. Dynamic modelling of exhaled respiratory droplets allows to account for aerosol persistence times in confined public spaces. The probability of infection by inhalation of aerosols when breathing in the same space can then be estimated using current estimates of viral load and infectivity of SARS-CoV-2. In line with the current known reproduction numbers, our study of transmission of SARS-CoV-2 suggests that aerosol transmission is an inefficient route, in particular from non or mildly symptomatic individuals.
Fully Automated Delineation of the Optic Radiation for Surgical Planning using Clinically Accessible Sequences
Authors: Reid Lee B , Martínez-Heras Eloy , Manjón Jose V , Jeffree Rosalind L. , Alexander Hamish , Trinder Julie , Solana Elisabeth , Llufriu Sara , Rose Stephen , Prior Marita , Fripp Jurgen
Published: July 2020

1

Quadrantanopia caused by inadvertent severing of Meyer’s Loop of the optic radiation is a well-recognised complication of temporal lobectomy for conditions such as epilepsy. Dissection studies indicate that the anterior extent of Meyer’s Loop varies considerably between individuals. Quantifying this for individual patients is thus an important step to improve the safety profile of temporal lobectomies. Previous attempts to delineate Meyer’s Loop using diffusion MRI tractography have had difficulty estimating its full anterior extent, required manual ROI placement, and/or relied on advanced diffusion sequences that cannot be acquired routinely in most clinics. Here we present CONSULT – a pipeline that can delineate the optic radiation from raw DICOM data in a completely automated way via a combination of robust preprocessing, segmentation, and alignment stages, plus simple improvements that bolster the efficiency and reliability of standard tractography. We tested CONSULT on 694 scans of predominantly healthy participants (538 unique brains), including both advanced acquisitions and simpler acquisitions that could be acquired in clinically acceptable timeframes. Delineations completed without error in 99.4% of the scans. The distance between Meyer’s Loop and the temporal pole closely matched both averages and ranges reported in dissection studies for all tested sequences. Median scan-rescan error of this distance was 1mm. When tested on two participants with considerable pathology, delineations were successful and realistic. Through this, we demonstrate not only how to identify Meyer’s Loop with clinically accessible sequences, but also that this can be achieved without fundamental changes to tractography algorithms or complex post-processing methods.

Highlights

We propose a fully automated means of delineating the optic radiation using diffusion MRI from DICOM data

Anatomical measurements from tractography of over 500 brains align well with previous dissection studies

The proposed pipeline works well with clinically accessible and advanced acquisitions

Median scan-rescan error was 1mm

Plausible tractography was generated when pathology was present
Is it safe to lift COVID-19 travel bans? The Newfoundland story
Authors: Linka Kevin , Rahman Proton , Goriely Alain , Kuhl Ellen
Published: July 2020

A key strategy to prevent a local outbreak during the COVID-19 pandemic is to restrict incoming travel. Once a region has successfully contained the disease, it becomes critical to decide when and how to reopen the borders. Here we explore the impact of border reopening for the example of Newfoundland and Labrador, a Canadian province that has enjoyed no new cases since late April, 2020. We combine a network epidemiology model with machine learning to infer parameters and predict the COVID-19 dynamics upon partial and total airport reopening, with perfect and imperfect quarantine conditions. Our study suggests that upon full reopening, every other day, a new COVID-19 case would enter the province. Under the current conditions, banning air travel from outside Canada is more efficient in managing the pandemic than fully reopening and quarantining 95% of the incoming population. Our study provides quantitative insights of the efficacy of travel restrictions and can inform political decision making in the controversy of reopening.

“There is one and only one way to absolutely prevent it and that is by establishing absolute isolation. It is necessary to shut off those who are capable of giving off the virus from those who are capable of being infected, or vice versa.” The Lessons Of The Pandemic, Science 1919.
Determinants of Burnout and Other Aspects of Psychological Well-Being in Healthcare Workers During the COVID-19 Pandemic: A Multinational Cross-Sectional Study
Authors: Scott Alasdair , Tan Benjamin YQ , Huak Chan Yiong , Sia Ching-Hui , Xian Chua Ying , Goh Ee Teng , Zbikowska Gabriela , Dykowska Grazyna , Martin Guy , Kinross James , Przybylowicz Jan , Fedorowski Jaroslaw , Beatty Jasmine Winter , Clarke Jonathan , Sim Kang , Abhiram Kanneganti , Flott Kelsey , Lim Lucas JH , Wells Mary , Denning Max , Almonte Melanie T , Tan Melanie , Mason Sam , Purkayastha Sanjay , Yalamanchili Seema , Markar Sheraz , Ooi Shirley BS , Chidambaran Swathikan , Lifeng Tan , Sharma Vijay K , Sounderajah Viknesh
Published: July 2020

Background

The Covid-19 pandemic has placed unprecedented pressure on healthcare systems and workers around the world. Such pressures may impact on working conditions, psychological wellbeing and perception of safety. In spite of this, no study has assessed the relationship between safety attitudes and psychological outcomes. Moreover, only limited studies have examined the relationship between personal characteristics and psychological outcomes during Covid-19.

Methods

From 22nd March 2020 to 18th June 2020, healthcare workers from the United Kingdom, Poland, and Singapore were invited to participate using a self-administered questionnaire comprising the Safety Attitudes Questionnaire (SAQ), Oldenburg Burnout Inventory (OLBI) and Hospital Anxiety and Depression Scale (HADS) to evaluate safety culture, burnout and anxiety/depression. Multivariate logistic regression was used to determine predictors of burnout, anxiety and depression.

Results

Of 3,537 healthcare workers who participated in the study, 2,364 (67%) screened positive for burnout, 701 (20%) for anxiety, and 389 (11%) for depression. Significant predictors of burnout included patient-facing roles: doctor (OR 2.10; 95% CI 1.49-2.95), nurse (OR 1.38; 95% CI 1.04-1.84), and ‘other clinical’ (OR 2.02; 95% CI 1.45-2.82); being redeployed (OR 1.27; 95% CI 1.02-1.58), bottom quartile SAQ score (OR 2.43; 95% CI 1.98-2.99), anxiety (OR 4.87; 95% CI 3.92-6.06) and depression (OR 4.06; 95% CI 3.04-5.42). Factors significantly protective for burnout included being tested for SARS-CoV-2 (OR 0.64; 95% CI 0.51-0.82) and top quartile SAQ score (OR 0.30; 95% CI 0.22-0.40). Significant factors associated with anxiety and depression, included burnout, gender, safety attitudes and job role.

Conclusion

Our findings demonstrate a significant burden of burnout, anxiety, and depression amongst healthcare workers. A strong association was seen between SARS-CoV-2 testing, safety attitudes, gender, job role, redeployment and psychological state. These findings highlight the importance of targeted support services for at risk groups and proactive SARS-CoV-2 testing of healthcare workers.
Forecasting hospital demand in metropolitan areas during the current COVID-19 pandemic and estimates of lockdown-induced 2nd waves
Authors: Capistrán Marcos A. , Capella Antonio , Andrés Christen J.
Published: July 2020

We present a forecasting model aim to predict hospital occupancy in metropolitan areas during the current COVID-19 pandemic. Our SEIRD type model features asymptomatic and symptomatic infections with detailed hospital dynamics. We model explicitly branching probabilities and non-exponential residence times in each latent and infected compartments. Using both hospital admittance confirmed cases and deaths, we infer the contact rate and the initial conditions of the dynamical system, considering breakpoints to model lockdown interventions and the increase in effective population size due to lockdown relaxation. The latter features let us model lockdown-induced 2nd waves. Our Bayesian approach allows us to produce timely probabilistic forecasts of hospital demand. We have applied the model to analyze more than 70 metropolitan areas and 32 states in Mexico.
An overview of current mental health in the general population of Australia during the COVID-19 pandemic: Results from the COLLATE project
Authors: Rossell Susan L , Neill Erica , Phillipou Andrea , Tan Eric J , Toh Wei Lin , Van Rheenen Tamsyn E , Meyer Denny
Published: July 2020

The novel coronavirus disease (COVID-19) poses significant mental health challenges globally; however, to date, there is limited community level data. This study reports on the first wave of data from the COLLATE project (COvid-19 and you: mentaL heaLth in AusTralia now survEy), an ongoing study aimed at understanding the impact of the COVID-19 pandemic on the mental health and well-being of Australians. This paper addresses prevailing primary concerns related to the COVID-19 pandemic, current levels of negative emotions and risk factors predicting these negative emotions. On April 1st to 4th 2020, 5158 adult members of the Australian general public completed an online survey. Participants ranked their top ten current primary concerns about COVID-19, and completed standardized measures to ascertain levels of negative emotions (specifically, depression, anxiety and stress). Socio-demographic information was also collected and used in the assessment of risk factors. The top three primary concerns were all related to the health and well-being of family and loved ones. As expected, levels of negative emotion were exceptionally high. Modelling of predictors of negative emotions established several risk factors related to demographic variables, personal vulnerabilities, financial stresses, and social distancing experiences; particularly being young, being female, or having a mental illness diagnosis. The data provides important characterization of the current mental health of Australians during the COVID-19 pandemic. Critically, it appears that specific groups in the Australian community may need special attention to ensure their mental health is protected during these difficult times. The data further suggests the need for immediate action to combat high levels of psychological distress, along with the exacerbation of mental health conditions, in relation to the COVID-19 pandemic in Australia. These results may provide some direction for international researchers hoping to characterize similar issues in other countries.
Regeneration of Functional Retinal Ganglion Cells by Neuronal Identity Reprogramming
Authors: Wei Xiaohu , Zhang Zhenhao , Zeng Huan-huan , Wang Xue-Feng , Zhan Wenrong , Qiao Na , Chang Zhen , Liu Lu , Fan Chengyu , Yang Ziwei , Li Xiaoming , Yang Yang , Liu Hongjun
Published: July 2020

Degeneration of retinal ganglion cells (RGCs) and their axons underlies vision loss in glaucoma and various optic neuropathies. There are currently no treatments available to restore lost vision in patients affected by these diseases. Regenerating RGCs and reconnecting the retina to the brain represent an ideal therapeutic strategy; however, mammals do not have a reservoir of retinal stem/progenitor cells poised to produce new neurons in adulthood. Here, we regenerated RGCs in adult mice by direct lineage reprogramming of retinal interneurons. We successfully converted amacrine and displaced amacrine interneurons into RGCs, and observed that regenerated RGCs projected axons into brain retinorecipient areas. They convey visual information to the brain in response to visual stimulation, and are able to transmit electrical signals to postsynaptic neurons, in both normal animals and in a diseased model. The generation of functional RGCs in adult mammals points to a therapeutic strategy for vision restoration in patients.
SARS-CoV-2 structural coverage map reveals state changes that disrupt host immunity
Authors: O’Donoghue Seán I. , Schafferhans Andrea , Sikta Neblina , Stolte Christian , Kaur Sandeep , Ho Bosco K. , Anderson Stuart , Procter James , Dallago Christian , Bordin Nicola , Adcock Matt , Rost Burkhard
Published: July 2020

In response to the COVID-19 pandemic, many life scientists are focused on SARS-CoV-2. To help them use available structural data, we systematically modeled all viral proteins using all related 3D structures, generating 872 models that provide detail not available elsewhere. To organise these models, we created a structural coverage map: a novel, one-stop visualization summarizing what is — and is not — known about the 3D structure of the viral proteome. The map highlights structural evidence for viral protein interactions, mimicry, and hijacking; it also helps researchers find 3D models of interest, which can then be mapped with UniProt, PredictProtein, or CATH features. The resulting Aquaria-COVID resource (https://aquaria.ws/covid) helps scientists understand molecular mechanisms underlying coronavirus infection. Based on insights gained using our resource, we propose mechanisms by which the virus may enter immune cells, sense the cell type, then switch focus from viral reproduction to disrupting host immune responses.

Significance

Currently, much of the COVID-19 viral proteome has unknown molecular structure. To improve this, we generated ∼1,000 structural models, designed to capture multiple states for each viral protein. To organise these models, we created a structure coverage map: a novel, one-stop visualization summarizing what is — and is not — known about viral protein structure. We used these data to create an online resource, designed to help COVID-19 researchers gain insight into the key molecular processes that drive infection. Based on insights gained using our resource, we speculate that the virus may sense the type of cells it infects and, within certain cells, it may switch from reproduction to disruption of the immune system.
Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle
Authors: Yoshioka Kiyoshi , Nagahisa Hiroshi , Miura Fumihito , Araki Hiromitsu , Kamei Yasutomi , Kitajima Yasuo , Seko Daiki , Nogami Jumpei , Tsuchiya Yoshifumi , Okazaki Narihiro , Yonekura Akihiko , Ohba Seigo , Sumita Yoshinori , Chiba Ko , Ito Kosei , Asahina Izumi , Ogawa Yoshihiro , Ito Takashi , Ohkawa Yasuyuki , Ono Yusuke
Published: July 2020

Skeletal muscle stem cells (satellite cells) are distributed throughout the body with heterogeneous properties that corresponds to region-specific pathophysiology. However, topographical genes that have functions remain unidentified in satellite cells of adult muscle. Here, we showed that expression of Homeobox (Hox)-A cluster genes, key regulators of the embryonic body plan, was robustly maintained in both muscles and satellite cells in adult mice and humans, which recapitulates their embryonic origin. We observed that regionally specific expressed Hox genes were linked to hypermethylation of the Hox-A locus. We examinedHoxa10inactivation in satellite cells and found it led to genomic instability and mitotic catastrophe, which resulted in a decline in the regionally specific regenerative ability of muscles in adult mice. Thus, our results showed that Hox gene expression profiles instill the embryonic history in satellite cells as positional memory, potentially modulating the region-specificity in adult skeletal muscles.
The role of alpha power in the suppression of anticipated distractors during verbal working memory
Authors: Sghirripa Sabrina , Graetz Lynton , Merkin Ashley , Rogasch Nigel C , Ridding Michael C , Semmler John G , Goldsworthy Mitchell R
Published: July 2020

As working memory (WM) is limited in capacity, it is important to direct neural resources towards processing task-relevant information while ignoring distractors. Neural oscillations in the alpha frequency band (8-12 Hz) have been suggested to play a role in the inhibition of task-irrelevant information during WM, although results are mixed, possibly due to differences in the type of WM task employed. Here, we examined the role of alpha power in inhibition of anticipated distractors of varying strength using a modified Sternberg task where the encoding and retention periods were temporally separated. We recorded EEG while 20 young adults completed the task and found: 1) slower reaction times in strong distractor trials compared to weak distractor trials; 2) increased alpha power in posterior regions from baseline prior to presentation of a distractor regardless of condition; and 3) no differences in alpha power between strong and weak distractor conditions. Our results suggest that parieto-occipital alpha power is increased prior to a distractor. However we could not find evidence that alpha power is further modulated by distractor strength.
Spatio-Temporal Correlates of Gene Expression and Cortical Morphology across Life Course and Aging
Authors: Qiu Anqi , Zhang Han , Kennedy Brian K. , Lee Annie
Published: July 2020

Evidence from independent neuroimaging and genetic studies supports the concept that brain aging mirrors development. However, it is unclear whether mechanisms linking brain development and aging provide new insights to delay aging and potentially reverse it. This study determined biological mechanisms and phenotypic traits underpinning brain alterations across the life course and in aging by examining spatio-temporal correlations between gene expression and cortical volumes (n=3391) derived from the life course dataset (3-82 years) and the aging dataset (55-82 years). We revealed that a large proportion of genes whose expression was associated with cortical volume across the life course were in astrocytes. These genes, which showed up-regulation during development and down-regulation during aging, contributed to fundamental homeostatic functions of astrocytes crucial, in turn, for neuronal functions. Included among these genes were those encoding components of cAMP and Ras signal pathways, as well as retrograde endocannabinoid signaling. Genes associated with cortical volumes in the aging dataset were also enriched for the sphingolipid signaling pathway, renin-angiotensin system (RAS), proteasome, and TGF-beta signaling pathway, which is linked to the senescence-associated secretory phenotype. Neuroticism, drinking, and smoking were the common phenotypic traits in the life course and aging, while memory was the unique phenotype associated with aging. These findings provide biological mechanisms and phenotypic traits mirroring development and aging as well as unique to aging.
Genetic Diversity and Structure ofOryza rufipogonGriff. Populations in the Philippines
Authors: Labarosa Sandy Jan E. , Sevilla Neah Rosandra , Tabanao Dindo Agustin A. , Baldo Nenita B. , Ebuña Helen L.V. , Jamago Joy M.
Published: July 2020

Oryza rufipogonGriff. or ‘Rufi’ is the wild progenitor of the cultivated rice,Oryza sativaL. In the Philippines, Rufi was previously known to be found only in Lake Apo, Bukidnon. However, a new population was identified in Lake Napalit in the same province. Based on previous morphological diversity assessment, both populations are unique for at least three characters, i.e., leaf, culm, and awn lengths. Environmental parameters such as rainfall and air temperature also differed between the two lakes. With these, an assessment of Rufi’s genetic diversity at the molecular level is beneficial to further ascertain its usefulness in rice breeding and gain insights on its conservation status. Thus, this study estimated the degree of genetic diversity and determined the population structure of 41 samples of natural Rufi populations in the Philippines using SSR markers. A total of 98 genome wide polymorphic SSR markers were selected to examine the genetic diversity and structure of Rufi populations, along with seven rice cultivars for comparison. Results showed that Philippine Rufi populations have lower genetic diversity compared to cultivated rice accessions and other Rufi populations in Southeast Asia and China. This low genetic diversity suggested that Rufi populations might be in a genetic bottleneck, perhaps due to observed unsustainable farming practices near their habitat and lack of awareness of their importance. A significant population structure and differentiation were determined using the STRUCTURE and phylogenetic analyses. Population differentiation might be due to geographic isolation which prevented gene flow between the two populations and the unique climatic conditions between the two lakes.
A Correspondence Between Normalization Strategies in Artificial and Biological Neural Networks
Authors: Shen Yang , Wang Julia , Navlakha Saket
Published: July 2020

A fundamental challenge at the interface of machine learning and neuroscience is to uncover computational principles that are shared between artificial and biological neural networks. In deep learning, normalization methods, such as batch normalization, weight normalization, and their many variants, help to stabilize hidden unit activity and accelerate network training, and these methods have been called one of the most important recent innovations for optimizing deep networks. In the brain, homeostatic plasticity represents a set of mechanisms that also stabilize and normalize network activity to lie within certain ranges, and these mechanisms are critical for maintaining normal brain function. In this survey, we discuss parallels between artificial and biological normalization methods at four spatial scales: normalization of a single neuron’s activity, normalization of synaptic weights of a neuron, normalization of a layer of neurons, and normalization of a network of neurons. We argue that both types of methods are functionally equivalent — i.e., they both push activation patterns of hidden units towards a homeostatic state, where all neurons are equally used — and that such representations can increase coding capacity, discrimination, and regularization. As a proof of concept, we develop a neural normalization algorithm, inspired by a phenomena calledsynaptic scaling, and show that this algorithm performs competitively against existing normalization methods on several datasets. Overall, we hope this connection will inspire machine learners in three ways: to uncover new normalization algorithms based on established neurobiological principles; to help quantify the trade-offs of different homeostatic plasticity mechanisms used in the brain; and to offer insights about how stability may not hinder, but may actually promote, plasticity.
Effect of corticosteroid treatment on 1376 hospitalized COVID-19 patients. A cohort study.
Authors: Albani Filippo , Fusina Federica , Granato Enza , Capotosto Cristina , Ceracchi Claudia , Gargaruti Riccardo , Santangelo Giovanni , Schiavone Luca , Taranto Maria Salvatrice , Tosati Cinzia , Vavassori Elena , Natalini Giuseppe
Published: July 2020

Background

Since the start of the novel coronavirus 2019 (COVID-19) pandemic, corticosteroid use has been the subject of debate. The available evidence is uncertain, and knowledge on the subject is evolving. The aim of our cohort study was to evaluate the association between corticosteroid therapy and hospital mortality, in patients hospitalized with COVID-19 after balancing for possible confounders.

Results

One thousand four hundred forty four patients were admitted to our hospital with a positive RT-PCR test for SARS-CoV-2, 559 patients (39%) were exposed to corticosteroids during hospital stay, 844 (61%) were not exposed to corticosteroids.In the cohort of patients exposed to corticosteroids, 171 (30.6%) died. In the cohort of patients not exposed to corticosteroids, 183 (21.7%) died (unadjusted p <0.001). Nonetheless, exposure to corticosteroids was not associated with in-hospital mortality after balancing with overlap weight propensity score (adjusted p = 0.25). Patients in the corticosteroids cohort had reduced risk of ICU admission (adjusted p <0.001).

Conclusions

Treatment with corticosteroids did not affect hospital mortality in patients with COVID-19 after balancing for confounders. A possible advantage of corticosteroid therapy was to reduce Intensive Care Unit admission, which could be useful in reducing pressure on the Intensive Care Units in times of limited resources, as during the COVID-19 pandemic.
HIGH VERSUS STANDARD DOSES OF CORTICOSTEROIDS IN COVID-19 PATIENTS WITH AN ACUTE RESPIRATORY DISTRESS SYNDROME: a controlled observational comparative study
Authors: Monreal Enric , de la Maza Susana Sainz , Natera-Villalba Elena , Beltrán-Corbellini Álvaro , Rodríguez-Jorge Fernando , Fernández-Velasco Jose Ignacio , Walo-Delgado Paulette , Muriel Alfonso , Zamora Javier , Alonso-Canovas Araceli , Fortún Jesús , Manzano Luis , Montero-Errasquín Beatriz , Costa-Frossard Lucienne , Masjuan Jaime , María Villar Luisa ,   for the COVID-HRC group
Published: July 2020

INTRODUCTION

Despite the increasing evidence of the benefit of corticosteroids for the treatment of moderate-severe Coronavirus disease 2019 (COVID-19) patients, no data are available about the potential role of high doses of steroids for these patients.

METHODS

All consecutive confirmed COVID-19 patients admitted to a single center were selected, including those treated with steroids and an acute respiratory distress syndrome (ARDS). Patients were allocated to the high doses (HD, ≥250mg/day of methylprednisolone) of corticosteroids or the standard doses (SD, ≤1.5mg/kg/day of methylprednisolone) at discretion of treating physician. The primary endpoint was the mortality between both cohorts and secondary endpoints were the risk of need for mechanical ventilation (MV) or death and the risk of developing a severe ARDS.

RESULTS

573 patients were included: 428 (74.7%) men, with a median (IQR) age of 64 (54–73) years. In HD cohort, a worse baseline respiratory situation was observed and male sex, older age and comorbidities were significantly more common. After adjusting by baseline characteristics, HD were associated with a higher mortality than SD (adjusted-OR 2.46, 95% CI 1.58 – 3.83, p<0.001) and with an increased risk of needing MV or death (adjusted-OR 2.50, p=0.001). Conversely, the risk of developing a severe ARDS was similar between groups. Interaction analysis showed that HD increased mortality exclusively in elderly patients.

CONCLUSION

Our real-world experience advises against exceeding 1-1.5mg/kg/day of corticosteroids for severe COVID-19 with an ARDS, especially in older subjects. This reinforces the rationale of modulating rather than suppressing immune responses in these patients.

In patients with severe COVID-19, high doses of corticosteroids are associated with a higher mortality and risk of need for mechanical ventilation or death compared to standard doses. This deleterious effect is mainly observed in the elderly.
The regulatory landscape of Arabidopsis thaliana roots at single-cell resolution
Authors: Dorrity Michael W. , Alexandre Cristina M. , Hamm Morgan , Vigil Anna-Lena , Fields Stanley , Queitsch Christine , Cuperus Josh
Published: July 2020

In plants, chromatin accessibility – the primary mark of regulatory DNA – is relatively static across tissues and conditions. This scarcity of accessible sites that are dynamic or tissue-specific may be due in part to tissue heterogeneity in previous bulk studies. To assess the effects of tissue heterogeneity, we apply single-cell ATAC-seq to A. thaliana roots and identify thousands of differentially accessible sites, sufficient to resolve all major cell types of the root. However, even this vast increase relative to bulk studies in the number of dynamic sites does not resolve the poor correlation at individual loci between accessibility and expression. Instead, we find that the entirety of a cell’s regulatory landscape and its transcriptome each capture cell type identity independently. We leverage this shared information on cell identity to integrate accessibility and transcriptome data in order to characterize developmental progression, endoreduplication and cell division in the root. We further use the combined data to characterize cell type-specific motif enrichments of large transcription factor families and to link the expression of individual family members to changing accessibility at specific loci, taking the first steps toward resolving the direct and indirect effects that shape gene expression. Our approach provides an analytical framework to infer the gene regulatory networks that execute plant development.
Conventional NK cells and tissue-resident ILC1s join forces to control liver metastasis
Authors: Ducimetière Laura , Lucchiari Giulia , Litscher Gioana , Nater Marc , Heeb Laura , Nuñez Nicolás Gonzalo , Wyss Laura , Burri Dominik , Vermeer Marijne , Gschwend Julia , Moor Andreas E. , Becher Burkhard , van den Broek Maries , Tugues Sonia
Published: July 2020

The liver is a major metastatic target organ, and little is known about the role of immunity in controlling hepatic metastases. Here, we discovered that the concerted and non-redundant action of two innate lymphocyte subpopulations, conventional NK cells (cNKs) and tissue-resident type I Innate Lymphoid Cells (trILC1s), is essential for anti-metastatic defense. Using different preclinical models for liver metastasis, we found that trILC1 control metastatic seeding, whereas cNKs restrain outgrowth. The antimetastatic activity of cNKs is regulated in a tumor type-specific fashion. Thereby, individual cancer cell lines orchestrate the emergence of cNK subsets with unique phenotypic and functional traits. Understanding cancer-cell- as well as innate-cell-intrinsic factors will allow the exploitation of hepatic innate cells for development of novel cancer therapies.

Significance

Innate lymphoid cells hold great promise for the treatment of metastases. Development of effective therapies based on these versatile immune cells, however, is hampered by our limited knowledge of their behavior in the metastatic niche. Here, we describe that defense against liver metastasis requires the collaboration between two innate lymphocyte subsets, conventional NK cells (cNKs) and tissue-resident type I innate lymphoid cells (trILC1s). We show that different cancers generate their own particular metastatic niche inducing specific changes in cNKs and trILC1s. Further, we uncover specific cNK subsets that can be manipulated to improve their anti-metastatic potential. Our work contributes to understanding how cancer-specific factors and hepatic innate lymphocytes exert mutual influence and how this can be exploited for therapeutic purposes.

Highlights

cNKs and trILC1s collaborate to control hepatic metastasis

trILC1s restrict seeding and cNKs control outgrowth of cancer cells in the liver

Individual cancer cell lines orchestrate a distinct metastatic niche

The metastatic niche dictates the phenotype and function of cNKs