bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcription factor BZR2 activates chitinase Cht20.2 transcription to confer resistance to wheat stripe rust
Authors: Bai Xingxuan , Zhan Gangming , Tian Shuxin , Peng Huan , Cui Xiaoyu , Islam Md Ashraful , Goher Farhan , Ma Youzhi , Kang Zhensheng , Xu Zhao-Shi , Guo Jun
Published: August 2021

The brassinosteroid pathway promotes a variety of physiological processes in plants and the brassinosteroid insensitive1-ethylmethane sulfonate suppressor (BES)/brassinazole-resistant (BZR) functions as one of its key regulators. We previously showed that the BES/BZR-type transcription factor TaBZR2 mediates the drought stress response in wheat (Triticum aestivum) by directly upregulating the transcriptional activity of glutathione S-transferase 1. However, the function of TaBZR2 in plants under biotic stresses is unknown. In this study, we found that transcript levels of TaBZR2 were upregulated in response to inoculation with wheat stripe rust fungus (Puccinia striiformis f. sp. tritici, Pst) and treatment with flg22 or an elicitor-like protein of Pst, Pst322. Wheat lines overexpressing TaBZR2 conferred increased resistance, whereas TaBZR2-RNAi lines exhibited decreased resistance to multiple races of Pst. TaBZR2 targeted the promoter of the chitinase gene TaCht20.2, activating its transcription. Knockdown of TaCht20.2 in wheat resulted in enhanced susceptibility to Pst, indicating the positive role of TaCht20.2 in wheat resistance. Upon Pst infection in vivo, the overexpression of TaBZR2 increased total chitinase activity, whereas RNAi-mediated silencing of TaBZR2 reduced total chitinase activity. Taken together, our results suggest that TaBZR2 confers broad-spectrum resistance to the stripe rust fungus by increasing total chitinase activity in wheat.
NATIONAL DIAGNOSTIC REFERENCE LEVELS AND ACHIEVABLE DOSES FOR STANDARD CT EXAMINATIONS IN SUDAN
Authors: Suliman I I , Bashier Einas H , Awad Mustafa , Ahmed Ibrahim , Mohamed Suhair , Ahmed Nada A
Published: August 2021

Radiation doses were determined to propose national diagnostic reference levels (NDRLs) and achievable doses (ADs) for computed tomography (CT) examinations in Sudan. Doses were estimated from retrospectively collected scan parameters for 1336 CT examinations of adult patients from 14 Sudanese hospitals using CT Expo 2.5 software. ADs and NDRLs were set at the 50th and 75th percentile of the hospital median dose distribution, respectively. The proposed CTDIvol (mGy) ADs ranged from: 10 (chest) to 64 (head), and that of the dose-length product (DLP; mGy.cm) ranged from 366 (chest) to 1225 (head). The proposed CTDIvol (mGy) NDRLs ranged from 15 kidney–ureter–bladder (KUB) to 79 (head), whereas that of the DLP (mGy.cm) ranged from 690 (chest) to 1490 (head). Current doses fell within the upper range of the doses presented in the literature emphasizing the need for implementation of the current ADs and NDRLs for CT to enhance patient protection and dose optimization in Sudan.
Mathematics and statistics distance learning: more than just online teaching
Authors: Hilliam Rachel , Goldrei Derek , Arrowsmith Gaynor , Siddons Alexander , Brown Cath
Published: August 2021

At the Open University, where students learn online and at a distance, the School of Mathematics and Statistics has for many years provided innovative ways of supporting students outside the ‘classroom’ environment so was well prepared to support students during the COVID-19 pandemic. These forms of support include online forums to help students with module choice and taster resources including diagnostic quizzes for students to self-assess their readiness to study individual modules and receive targeted support. Since 2017, these resources, and more, have been incorporated into a multi-functional student-facing website. The website enables all units, both academic and non-academic, to provide consistent academic, pastoral and social support to students studying mathematics and statistics modules online. By focusing on the different stages of a student’s journey, the website provides a one-stop shop for students to self-serve and obtain appropriate support at each point in their own student lifecycle. Data gathered on the frequency of use of the website, together with the results from staff and student questionnaires, have provided insight into how students and staff use the website. The evaluation highlights the need for clear signposting to such resources. In addition, the wide range of resources which enable students to make informed module choices is shown to be particularly important for staff who provide pastoral and academic support to students.
Unique protein features of SARS-CoV-2 relative to other Sarbecoviruses
Authors: Cotten Matthew , Robertson David L , Phan My V T
Published: August 2021

Defining the unique properties of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein sequences has potential to explain the range of Coronavirus Disease 2019 severity. To achieve this we compared proteins encoded by all Sarbecoviruses using profile Hidden Markov Model similarities to identify protein features unique to SARS-CoV-2. Consistent with previous reports, a small set of bat- and pangolin-derived Sarbecoviruses show the greatest similarity to SARS-CoV-2 but are unlikely to be the direct source of SARS-CoV-2. Three proteins (nsp3, spike, and orf9) showed regions differing between the bat Sarbecoviruses and SARS-CoV-2 and indicate virus protein features that might have evolved to support human infection and/or transmission. Spike analysis identified all regions of the protein that have tolerated change and revealed that the current SARS-CoV-2 variants of concern have sampled only a fraction (∼31 per cent) of the possible spike domain changes which have occurred historically in Sarbecovirus evolution. This result emphasises the evolvability of these coronaviruses and the potential for further change in virus replication and transmission properties over the coming years.
Taxonomic challenges posed by discordant evolutionary scenarios supported by molecular and morphological data in the Amazonian Synallaxis rutilans group (Aves: Furnariidae)
Authors: Stopiglia Renata , Barbosa Waleska , Ferreira Mateus , Raposo Marcos A , Dubois Alain , Harvey Michael G , Kirwan Guy M , Forcato Giovanna , Bockmann Flavio A , Ribas Camila C
Published: August 2021

Alpha taxonomy endeavours to propose a coherent vision of existing species and, simultaneously, to individualize the natural entities useful to understand evolutionary processes. This ideal is especially difficult when available data lack congruence. Here we address the polytypic species Synallaxis rutilans (ruddy spinetail), a suboscine passerine widely distributed in the Amazon Basin and whose taxonomy could, potentially, aid our understanding of processes shaping its biodiversity. Combining genetic [genomic ultraconserved elements (UCE) and mtDNA] and morphological data, we demonstrate that while delimitation of genetic lineages and their phylogenetic relationships are strongly associated with classic Amazonian geographic barriers, such as rivers, different coloration patterns appear to be more associated with local selection processes for phenotype. Employing an evolutionary approach, whereby the species is considered a taxonomic category, rather than a nomenclatural rank, we propose to recognize five species: S. amazonica, S. caquetensis, S. dissors, S. omissa and S. rutilans. The taxonomic arrangement proposed here permits better understanding of the similarities and differences among taxa from different areas of endemism, and represents patterns of genetic and morphological diversity resulting from distinct processes acting across certain time frames. This arrangement draws attention to the importance of understanding the evolutionary processes operating in the complex and constantly changing Amazonian landscape.
The role of soils in regulation of freshwater and coastal water quality
Authors: Cheng Kun , Xu Xiangrui , Cui Liqiang , Li Yunpeng , Zheng Jufeng , Wu Wenao , Sun Jianfei , Pan Genxing
Published: August 2021

Water quality regulation is an important ecosystem service function of soil. In this study, the mechanism by which soil regulates water quality was reviewed, and the effects of soil management on water quality were explored. A scientometrics analysis was also conducted to explore the research fields and hotspots of water quality regulation of soil in the past 5 years. This review found that the pollutants entering the soil can be mitigated by precipitation, adsorption and desorption, ion exchange, redox and metabolic decomposition. As an optimal substrate, soil in constructed wetlands has perfect performance in the adsorption and passivation of pollutants such as nitrogen, phosphorus and heavy metals in water, and degradation of pesticides and emerging contaminants. Mangrove wetlands play an important role in coastal zone protection and coastal water quality restoration. However, the excessive application of agricultural chemicals causes soil overload, which leads to the occurrence of agricultural non-point source pollution. Under the dual pressures of climate change and food insecurity in the future, developing environmentally friendly and economically feasible sustainable soil management measures is crucial for maintaining the water purification function of soil by relying on the accurate quantification of soil function based on big data and modelling.

This article is part of the theme issue ‘The role of soils in delivering Nature's Contributions to People’.
The role of soil in the contribution of food and feed
Authors: Silver W. L. , Perez T. , Mayer A. , Jones A. R.
Published: August 2021

Soils play a critical role in the production of food and feed for a growing global population. Here, we review global patterns in soil characteristics, agricultural production and the fate of embedded soil nutrients. Nitrogen- and organic-rich soils supported the highest crop yields, yet the efficiency of nutrient utilization was concentrated in regions with lower crop productivity and lower rates of chemical fertilizer inputs. Globally, soil resources were concentrated in animal feed, resulting in large inefficiencies in nutrient utilization and losses from the food system. Intercontinental transport of soil-derived nutrients displaced millions of tonnes of nitrogen and phosphorus annually, much of which was ultimately concentrated in urban waste streams. Approximately 40% of the global agricultural land area was in small farms providing over 50% of the world's food and feed needs but yield gaps and economic constraints limit the ability to intensify production on these lands. To better use and protect soil resources in the global food system, policies and actions should encourage shifts to more nutrient-efficient diets, strategic intensification and technological improvement, restoration and maintenance of soil fertility and stability, and enhanced resilience in the face of global change.

This article is part of the theme issue ‘The role of soils in delivering Nature's Contributions to People’.
Earth as construction material in the circular economy context: practitioner perspectives on barriers to overcome
Authors: Morel Jean-Claude , Charef Rabia , Hamard Erwan , Fabbri Antonin , Beckett Chris , Bui Quoc-Bao
Published: August 2021

The need for a vast quantity of new buildings to address the increase in population and living standards is opposed to the need for tackling global warming and the decline in biodiversity. To overcome this twofold challenge, there is a need to move towards a more circular economy by widely using a combination of alternative low-carbon construction materials, alternative technologies and practices. Soils or earth were widely used by builders before World War II, as a primary resource to manufacture materials and structures of vernacular architecture. Centuries of empirical practices have led to a variety of techniques to implement earth, known as rammed earth, cob and adobe masonry among others. Earth refers to local soil with a variable composition but at least containing a small percentage of clay that would simply solidify by drying without any baking. This paper discusses why and how earth naturally embeds high-tech properties for sustainable construction. Then the potential of earth to contribute to addressing the global challenge of modern architecture and the need to re-think building practices is also explored. The current obstacles against the development of earthen architecture are examined through a survey of current earth building practitioners in Western Europe. A literature review revealed that, surprisingly, only technical barriers are being addressed by the scientific community; two-thirds of the actual barriers identified by the interviewees are not within the technical field and are almost entirely neglected in the scientific literature, which may explain why earthen architecture is still a niche market despite embodying all the attributes of the best construction material to tackle the current climate and economic crisis.

This article is part of the theme issue ‘The role of soils in delivering Nature's Contributions to People’.
The role of soils in learning and inspiration, physical and psychological experiences, and in supporting identities
Authors: McElwee Pamela
Published: August 2021

This paper reviews the literature on soil and nature's contributions to people (NCP) around learning and inspiration, physical and psychological experiences, and supporting identities, revealing a range of relationships to imagining, understanding and experiencing soil. Often labelled elsewhere as ‘cultural ecosystem services’, these NCP provide a range of benefits that are mostly non-material, non-consumptive and intangible. The review finds that NCP framings help to highlight how soils have contributed to inspiring learning and creative works, like art; to mental and physical health benefits, such as through recreation and gardening; and to cultural identities and practices, including religious practices and efforts for social justice. Overall, soils have played a large role in human creative endeavours, are the root of significant relationships to the environment and can be conceptualized through key metaphors, ideas and theory as a bridge linking culture and nature together. Yet despite the wide-ranging contributions of soils to these NCP, the literature remains uneven and much more remains to be understood, including how relational values of care and stewardship with soils can be fostered and how attention to the co-produced ‘biosocial’ nature of soil can help improve practices for soil health.

This article is part of the theme issue ‘The role of soils in delivering Nature's Contributions to People’.
Soil-derived Nature's Contributions to People and their contribution to the UN Sustainable Development Goals
Authors: Smith Pete , Keesstra Saskia D. , Silver Whendee L. , Adhya Tapan K. , De Deyn Gerlinde B. , Carvalheiro Luísa G. , Giltrap Donna L. , Renforth Phil , Cheng Kun , Sarkar Binoy , Saco Patricia M. , Scow Kate , Smith Jo , Morel Jean-Claude , Thiele-Bruhn Sören , Lal Rattan , McElwee Pam
Published: August 2021

This special issue provides an assessment of the contribution of soils to Nature's Contributions to People (NCP). Here, we combine this assessment and previously published relationships between NCP and delivery on the UN Sustainable Development Goals (SDGs) to infer contributions of soils to the SDGs. We show that in addition to contributing positively to the delivery of all NCP, soils also have a role in underpinning all SDGs. While highlighting the great potential of soils to contribute to sustainable development, it is recognized that poorly managed, degraded or polluted soils may contribute negatively to both NCP and SDGs. The positive contribution, however, cannot be taken for granted, and soils must be managed carefully to keep them healthy and capable of playing this vital role. A priority for soil management must include: (i) for healthy soils in natural ecosystems,protectthem from conversion and degradation; (ii) for managed soils,managein a way to protect and enhance soil biodiversity, health and sustainability and to prevent degradation; and (iii) for degraded soils, restore to full soil health. We have enough knowledge now to move forward with the implementation of best management practices to maintain and improve soil health. This analysis shows that this is not just desirable, it is essential if we are to meet the SDG targets by 2030 and achieve sustainable development more broadly in the decades to come.

This article is part of the theme issue ‘The role of soils in delivering Nature's Contributions to People’.
Removal of the race coefficient and adjustment to individual BSA provide the most accurate estimation for GFR in Black adolescents
Authors: Bielopolski D , Bentur O , Singh N , Vaughan R , Charytan DM , Kost RG , Tobin JN
Published: August 2021

Introduction

Obesity is more prevalent among minorities, increasing the risk for cardio-renal morbidity. We explored interactions between race, body mass index (BMI), and the risk of hyperfiltration associated with Obesity Related Glomerulopathy (ORG).

Methods

We created a cohort of women and girls ages 12-21 from the New York Metropolitan area using electronic health records. Glomerular filtration rate (GFR) was estimated in three ways: I) using the standard age recommended formulae, II) eGFRr – without a race-specific coefficient, and III) Absolute eGFRr – combing removal of the race coefficient and adjusting to individual body surface area. Multivariate logistic regression was used to analyze the relative contribution of risk factors for ORG associated hyperfiltration, defined by a threshold of ≥135ml/min/1.73m2. Bland Altman analysis and Pearson’s coefficient assessed the correlation of each formula with creatinine clearance (CrCl).

Results

7315 Black and 15,102 non-Black women and girls had simultaneous evaluation of kidney function and body measures. CrCl was available in 207 non-Black and 107 Black individuals as an internal validation. Simultaneous removal of the race coefficient and adjustment to individual BSA estimated GFR most accurately compared to CrCl, across BMI groups and between races. Hyperfiltration was more frequent in obese Black compared to non-Black individuals when using standard eGFR (20% vs. 6.5% respectively) but had a lower frequency after eliminating the race-specific coefficient (4.5% vs. 6.5%). Black race was independently associated with a higher risk of hyperfiltration with standard eGFR calculations (OR=3.43, 95% CI 2.95-3.99) and with lower risk when estimated by eGFRr (OR=0.56, 95% CI 0.45-0.70). Simultaneous removal of the race coefficient from GFR calculation and adjustment to individual BSA attenuated the difference in risk between races (OR=0.8, 95% CI 0.68-0.94). The combined correction agreed well with creatinine clearance (Pearson’s correlation coefficient r=0.64, 0.52 and 0.52 for absolute eGFRr, eGFR and eGFRr respectively.

Conclusions

Removal of the race coefficient from GFR estimating equations obscures obesity associated hyperfiltration among Black adolescents. This correction should be accompanied by adjustment to individual BSA to improve estimation of GFR to avoid misclassification of obesity related hyperfiltration.
CandyCodes: Simple universally unique edible identifiers for confirming the authenticity of pharmaceuticals
Authors: Grover William H.
Published: August 2021

Counterfeit or substandard medicines adversely affect the health of millions of people and cost an estimated $200 billion USD annually. Their burden is greatest in developing countries, where the World Health Organization estimates that one in ten medical products are fake. In this work, I describe a simple addition to the existing drug manufacturing process that imparts an edible universally unique physical identifier to each pill, tablet, capsule, caplet, etc. This technique uses nonpareils (also called sprinkles and “hundreds and thousands”), tiny inexpensive multicolor candy spheres that are normally added to other candies or desserts as decorations. If nonpareils are applied at random to a pill immediately after manufacture, the specific pattern they form is unlikely to ever be repeated by random chance; this means that the pattern (or “CandyCode”) can be used to uniquely identify the pill and distinguish it from all other pills. By taking a photograph of each CandyCoded pill after manufacture and recording the location and color of each nonpareil, a manufacturer can construct a database containing the CandyCodes of all known-authentic pills they produce. A consumer can then simply use a cellphone to photograph a pill and transfer its image to the manufacturer’s server, which determines whether the pill’s CandyCode matches a known-good CandyCode in their database (meaning that the pill is authentic) or does not have a match in the database (in which case the consumer is warned that the pill may be counterfeit and should not be consumed). To demonstrate the feasibility of using random particles as universal identifiers, I performed a series of experiments using both real CandyCodes (on commercially produced chocolate candies) and simulated CandyCodes (generated by software). I also developed a simple method for converting a CandyCode photo to a set of strings for convenient storage and retrieval in a database. Even after subjecting CandyCodes to rough handling to simulate shipping conditions, the CandyCodes were still easily verifiable using a cellphone camera. A manufacturer could produce at least 1017CandyCoded pills—41 million for each person on Earth—and still be able to uniquely identify each CandyCode. By providing universally-unique IDs that are easy to manufacture but hard to counterfeit, require no alteration of the existing drug formation and minimal alteration of the manufacturing process, and need only a cameraphone for verification, CandyCodes could play an important role in the fight against fraud in pharmaceuticals and many other products.
Finding effective therapeutic approaches for motor rehabilitation after stroke: Insights from a thematic analysis
Authors: Ranganathan Rajiv , Doherty Carson , Gussert Michael , Kaplinski Eva , Koje Mary , Krishnan Chandramouli
Published: August 2021

Despite tremendous advances in the treatment and management of stroke, restoring motor and functional outcomes after stroke continues to be a major clinical challenge. Given the wide range of approaches used in motor rehabilitation, several commentaries have highlighted the lack of a clear scientific premise for different interventions as one critical factor that has led to suboptimal study outcomes. To examine this issue in greater detail, we conducted a thematic analysis of randomized controlled trials in stroke rehabilitation over a 2-year period from 2019-2020. Our results revealed three primary findings: (i) most studies did not provide an explicit rationale for why the treatment would be expected to work, (ii) there was not a close correspondence between the active ingredients mentioned versus the active ingredients measured in the study, and (iii) multimodal approaches that involved more than one therapeutic approach tended to be combined in an ad-hoc fashion, indicating the lack of a targeted approach. These results highlight the need for strengthening cross-disciplinary connections between basic science and clinical studies, and the need for structured development and testing of therapeutic approaches to find more effective treatment interventions.
Playing the Harmonica with Chronic Obstructive Pulmonary Disease. A qualitative study
Authors: Lewis A , Conway J , Middleton J , Startup C , Wyatt J
Published: August 2021

Introduction

Pulmonary Rehabilitation (PR) is the gold standard, group-based intervention for individuals with Chronic Obstructive Pulmonary Disease (COPD). However, accessibility and adherence to PR is sub-optimal. Arts in Health interventions also improve health outcomes for people living with long term conditions. Playing the harmonica with COPD could be clinically beneficial. However, little is known about the patient experiences of playing the harmonica.

Methods

A qualitative, interpretivist, phenomenological study was undertaken, exploring COPD patient experiences of harmonica playing with a group of others living with chronic respiratory disease. Semi-structured interviews were completed, transcribed, and reflexive inductive thematic analysis performed.

Results

Eight people with COPD were interviewed. Thematic analysis generated five themes. Themes included “Hard in the beginning”, “Holding the condition”, “Breathing control”, “Gives you a high” and “Needing the Zoom class”. Playing the harmonica with COPD is difficult at first, particularly drawing a breath through the harmonica. With practice, experience in a fun activity, and quality teaching, individuals were able to become more attuned and embodied with their breathing. As breathing became easier the songs, rather than breathing, became the focus, and participants were able to escape living with respiratory disease when playing. The group was a priority in the weekly lives of participants, even though the buzz of being part of a group was lost.

Discussion

Playing the harmonica requires a different way of breathing and offers a breathing control strategy. Participants also reported the harmonica helped airway clearance and enabled a continued, regular social interaction through COVID-19. The results of this study compliment previous quantitative results and are relevant to physiotherapy. Further mechanistic studies and randomised controlled trials are needed to investigate the biopsychosocial benefits of playing the harmonica with COPD.
Booster and anergic effects of the Covishield vaccine among healthcare workers in South India
Authors: Kannian Priya , Mahanathi Pasuvaraj , Ashwini Veeraraghavan , Kumarasamy Nagalingeswaran
Published: August 2021

Covishield (same as ChAdOx1) vaccine was rolled out in January 2021 against SARS-CoV2 in India. Although studies show good efficacy after two doses, there is limited data on the fate of the elicited antibody responses over time in groups with or without prior exposure to SARS-CoV2. Therefore, in this study we proposed to test naïve or previously exposed healthcare workers (HCWs) longitudinally after both doses for anti-SARS-CoV2 spike antibody (ASSA) levels. Serum samples were collected from 205 HCWs at days 14 and 28 after first dose, and at days 14, 28 and 3-months after second dose. ASSA levels were quantitated by ECLIA method. Non-responder rate was 17% (35/205) on day 14 and 2% (5/205) on day 28 after the first dose. After the second dose, the responder rate was 100%. Non-responder rate was significantly higher among males (p<0.00001) and senior citizens (p=0.008). The second dose boosted a 27-fold increase in the COVID-19 naïve (CN) group, but caused a 1.5-fold decline in the previously exposed groups. By three months, the antibody levels declined 3-4-folds in all the groups. In spite of high antibody levels (GM-1007 U/ml) after the second dose, 14% developed mild breakthrough infections (BTI). The booster effect was significantly higher when given 10-14 weeks later. The responder rate for Covishield was 98% after first dose and 100% after second dose. The vaccine elicited a prime-boost effect in CN HCWs and a boost-anergy effect in the previously exposed HCWs. ASSA levels began to decline proportionately by three months.
HIF1alpha Cardioprotection in COVID-19 Patients
Authors: Wang Bingyan J. , Vadakke-Madathil Sangeetha , Croft Lori B. , Brody Rachel I. , Chaudhry Hina W.
Published: August 2021

Importance

SARS-CoV-2 infection directly causes severe acute respiratory illness, leading to systemic tissue hypoxia and ischemia including the heart. Myocardial cytopathy associated with hypoxic response has been largely overlooked in COVID-19 patients. Additionally, histology analysis and cardiac function of COVID-19 cases are often reported separately, rendering an incomplete understanding of COVID-19 cardiac symptoms.

Objective

To examine the relationship between myocardial cellular responses to hypoxic stress versus cardiac functional alterations within the same COVID-19 patients.

Design, Setting, and Participants

Cellular hypoxia Inducible Factor 1 alpha (HIF1α) expression was analyzed by immunohistochemistry using post-mortem COVID-19 heart and lung tissues with known cardiac echocardiography records from a total of 8 patients. Clinical echocardiography data were obtained from Mount Sinai Heart between March to December, 2020. All gender and age groups were considered as long as cardiac involvement meets the preserved (EF > 50%) or moderate to severe (EF < 45%) criteria with confirmed SARS-CoV-2 infection. Cell-type specific subcellular localization of HIF1α expression and nuclear stability was examined by immunohistochemistry and transmission electronic microscopy (TEM). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to quantify apoptosis.

Main Outcomes and Measures

No planned outcomes of this study as this is a retrospective analysis based on post-mortem specimens exclusively.

Results

Cardiac HIF1α expression was found to be significantly higher in patients with preserved EF levels than it was in the low EF group. In the preserved EF group, HIF1α is protective against apoptosis predominantly in endothelial cells and cardiac fibroblasts. In the low EF group, HIF1α protects cardiomyocyte nuclear integrity as evident by its nuclear accumulation with nuclear envelope preservation.

Conclusions and Relevance

This study establishes a direct link of cardiac cellular responses to hypoxic stress with matching functional and histological data, serving as one of the first studies to bridge previous stand-alone clinical data and cellular data. The protective role of HIF1α in hearts may help predict cardiac involvement in not only COVID-19 patients, but also decipher the underlying mechanisms in other forms of viral cardiomyopathy.

KEY POINTS

Question

Are hypoxic signaling pathways associated with cardiac functional alterations in COVID-19 patients?

Findings

Cardiac HIF1α expression of COVID-19 patients with EF>50% or EF<45% was analyzed and quantified. Increased cardiac HIF1α+ cells were found in patients with higher EF. HIF1α+ endothelial cells are resistant to apoptosis, and HIF1α+ cardiomyocytes are able to retain nuclear envelope under hypoxic stress.

Meaning

HIF1α is cardioprotective in hearts of COVID-19 patients.
COVID-19 mortality prediction model, 3C-M, built for use in resource limited settings - understanding the relevance of neutrophilic leukocytosis in predicting disease severity and mortality
Authors: Agarwal Niharika , Dua Devika , Sud Ritika , Yadav Madhur , Agarwal Aparna , Vijayan Vijesh
Published: August 2021

In this study, a combination of clinical and hematological information, collected on day of presentation to the hospital with pneumonia, was evaluated for its ability to predict severity and mortality outcomes in COVID-19. Ours is a retrospective, observational study of 203 hospitalized COVID-19 patients. All of them were confirmed RT-PCR positive cases. We used simple hematological parameters (total leukocyte count, absolute neutrophil count, absolute lymphocyte count, neutrophil to lymphocyte ration and platelet to lymphocyte ratio); and a severity classification of pneumonia (mild, moderate and severe) based on a single clinical parameter, the percentage saturation of oxygen at room air, to predict the outcome in these cases. The results show that a high absolute neutrophil count on day of onset of pneumonia symptoms correlated strongly with both severity and survival in COVID-19. In addition, it was the primary driver of an initial high neutrophil-to-lymphocyte ratio (NLR) observed in patients with severe disease. The effect of low lymphocyte count was not found to be very significant in our cohort. Multivariate logistic regression was done using Python 3.7 to assess whether these parameters can adequately predict survival. We found that clinical severity and a high neutrophil count on day of presentation of pneumonia symptoms could predict the outcome with 86% precision. This model is undergoing further evaluation at our centre for validation using data collected during the second wave of COVID-19. We present the relevance of an elevated neutrophil count in COVID-19 pneumonia and review the advances in research which focus on neutrophils as an important effector cell of COVID-19 inflammation.
Rapid antigen testing for SARS-CoV-2 infection in a university setting in Ireland: learning from a 6-week pilot study
Authors: Barry Gerald , McCarney Catherine , Farrelly Marc , Breathnach Rory , Mooney Carmel , More Simon J.
Published: August 2021

Objectives

With the ongoing circulation of SARS-CoV-2 in countries across the world it is essential to identify effective ways to reduce the risk of infection while allowing society to function as close to ‘normal’ as possible. Serial testing using rapid lateral flow antigen tests is a possible way to do this by screening populations in a targeted way, identifying infectious (both symptomatic and asymptomatic) people and removing them from circulation while infectious. To make rapid antigen testing effective, high levels of participation are important. This study was designed to evaluate the establishment of a testing programme in a university setting and assess some of the factors that impact participation in such a study among both staff and students.

Study Design

Observational, survey

Methods

A trial period of SARS-CoV-2 rapid testing using the Abbott Panbio rapid antigen test was set up and staff and students based in the University College Dublin Veterinary Hospital were asked to take part voluntarily for 6 weeks. Following the trial period, we used a questionnaire to evaluate satisfaction and to understand some reasons behind participation or lack thereof.

Results

Overall, almost all respondents to the survey stated that they were happy with having a testing programme present in the workplace and it helped to reduce anxiety associated with COVID-19. Findings indicated that staff and students did not participate equally in the voluntary testing programme. The findings also highlighted that intrinsic motivations and extrinsic motivations for participation differ. For example, participation among staff was much higher than among students, motivational messaging focused on protecting others did not resonate with students as much as staff, convenience was a key factor driving participation in both cohorts and the pressure of being forced to miss class (if positive) close to exam time provided motivation to students to avoid testing.

Conclusions

Introducing antigen testing into a workplace helped to reduce overall anxiety associated with the potential impact of COVID-19, but achieving good participation was challenging. Participation is key to a successful, campus wide antigen testing programme but reaching high levels of participation is not straightforward and can not be taken for granted. Different motivations drive participation in different cohorts and different messaging/incentivisation is needed to encourage participation in those different cohorts. The findings reported here should inform any SARS-CoV-2 testing programme that will run in these types of settings in the future.
Rapid transmission of coronavirus disease 2019 within a religious sect in South Korea: a mathematical modeling study
Authors: Kim Jong-Hoon , Lee Hyojung , Won Yong Sul , Son Woo-Sik , Im Justin
Published: August 2021

Rapid transmission of coronavirus disease 2019 (COVID-19) was observed in the Shincheonji Church of Jesus, a religious sect in South Korea. The index case was confirmed on February 18, 2020 in Daegu City, and within two weeks, 3,081 connected cases were identified. Doubling times during these initial stages (i.e., February 18 – March 2) of the outbreak were less than 2 days. A stochastic model fitted to the time series of confirmed cases suggests that the basic reproduction number (R0) of COVID-19 was 8.5 [95% credible interval (CrI): 6.3, 10.9] among the church members, whereas (R0 = 1.9 [95% CrI: 0.4, 4.4]) in the rest of the population of Daegu City. The model also suggests that there were already 4 [95% CrI: 2, 11] undetected cases of COVID-19 on February 7 when the index case reportedly presented symptoms. The Shincheonji Church cluster is likely to be emblematic of other outbreak-prone populations where R0 of COVID-19 is higher. Understanding and subsequently limiting the risk of transmission in such high-risk places is key to effective control.

Highlights

Basic reproduction number (R0) of COVID-19 in a religious community of Shincheonji Church of Jesus was estimated to be 8.5 [95% credible interval (CrI): 6.3, 10.9], which is more than 4 times larger than the general population (R0 = 1.9 [95% CrI: 0.4, 4.4])

There were estimated 4 [95% CrI: 2, 11] undetected cases when the index case from the religious community reported symptom on February 7.

The Shincheonji Church cluster is likely to be emblematic of other outbreak-prone populations where R0 of COVID-19 is higher. Understanding and subsequently limiting the risk of transmission in such high-risk places is key to effective control.
Fear memory-associated synaptic and mitochondrial changes revealed by deep learning-based processing of electron microscopy data
Authors: Liu Jing , Qi Junqian , Chen Xi , Li Zhenchen , Hong Bei , Ma Hongtu , Li Guoqing , Shen Lijun , Liu Danqian , Kong Yu , Xie Qiwei , Han Hua , Yang Yang
Published: August 2021

Serial section electron microscopy (ssEM) can provide comprehensive 3D ultrastructural information of the brain with exceptional computational cost. Targeted reconstruction of subcellular structures from ssEM datasets is less computationally demanding but still highly informative. We thus developed a Region-CNN-based deep learning method to identify, segment, and reconstruct synapses and mitochondria to explore the structural plasticity of synapses and mitochondria in the auditory cortex of mice subjected to fear conditioning. Upon reconstructing over 135,000 mitochondria and 160,000 synapses, we found that fear conditioning significantly increases the number of mitochondria but decreases their size, and promotes the formation of multi-contact synapses comprising a single axonal bouton and multiple postsynaptic sites from different dendrites. Modeling indicates that such multi-contact configuration increases the information storage capacity of new synapses by over 50%. With high accuracy and speed in reconstruction, our method yields structural and functional insight into cellular plasticity associated with fear learning.
The impact of obesity; key features of raised intracranial pressure and clinical sequalae in rodents
Authors: Westgate Connar Stanley James , Hagen Snorre Malm , Israelsen Ida Marchen Egerod , Hamann Steffen , Jensen Rigmor Højland , Eftekhari Sajedeh
Published: August 2021

Elevated intracranial pressure (ICP) is observed in many brain disorders. Obesity has been linked to ICP pathogenesis in disorders such as idiopathic intracranial pressure (IIH). We investigated the effect of diet induced obesity (DIO) on ICP and clinically relevant sequelae.

Rats were fed either a control or high fat diet. Following weight gain long term ICP, headache behavior, body composition and retinal outcome were examined. Post-hoc analysis of retinal histology and molecular analysis of choroid plexus and trigeminal ganglion (TG) were performed.

DIO rats demonstrated raised ICP by 55% which correlated with the abdominal fat percentage and increased non-respiratory slow waves, suggestive of altered cerebral compliance. Concurrently, DIO rats demonstrated a specific cephalic cutaneous allodynia which negatively correlated with the abdominal fat percentage. This sensitivity was associated with increased expression of headache markers in TG. Additionally, DIO rats had an in vivo increased retinal nerve fiber layer thickness associated with raised ICP with a subsequent post-hoc demonstration of neuroretinal degeneration.

This study demonstrates for the first time that DIO leads to raised ICP and subsequent clinically relevant symptom development. This novel model of non-traumatic raised ICP could expand the knowledge regarding disorders with elevated ICP such as IIH.
Large field-of-view incoherent volumetric imaging in living human retina by confocal oblique scanning laser ophthalmoscopy
Authors: Shao Wenjun , Yi Ji
Published: August 2021

Three-dimensional (3D) volumetric imaging of the human retina is instrumental to monitor and diagnose blinding conditions. Although coherent retinal imaging is well established by optical coherence tomography, it is still a large void for incoherent volumetric imaging in the human retina. Here, we report confocal oblique scanning laser ophthalmoscopy (CoSLO), to fill that void and harness incoherent optical contrast in 3D. CoSLO uses oblique scanning laser and remote focusing to acquire depth signal in parallel, avoid the lengthy z-stacking, and image a large field of view (FOV). In addition, confocal gating is introduced by a linear sensor array to improve the contrast and resolution. For the first time, we achieved incoherent 3D human retinal imaging with >20° viewing angle within only 5 seconds. The depth resolution is ∼45 micronsin vivo. We demonstrated label-free incoherent contrast by CoSLO, revealing unique features in the retina. CoSLO will be an important technique for clinical care of retinal conditions and fundamental vision science, by offering unique volumetric incoherent contrasts.
Evidence Accumulates for Individual Attributes during Value-Based Decisions
Authors: Lee Douglas G. , Hare Todd A.
Published: August 2021

When choosing between different options, we tend to consider specific attribute qualities rather than deliberating over some general sense of the options’ overall values. The importance of each attribute together with its quality will determine our preference rankings over the available alternatives. Here, we test the hypothesis that the most prominent class of model for simple decisions – sequential sampling or evidence accumulation to bound – can be bolstered by explicitly incorporating variables related to individual attributes in addition to the standard usage of overall value estimates. We examine six datasets in which participants evaluated snack foods both in terms of overall value and individual attributes, then chose between pairs of the same snacks, and show that only models that explicitly incorporate information about the individual attributes are able to reproduce fundamental patterns in the choice data, such as the influence of attribute disparity on decisions, and such models provide quantitatively better fits to the choice outcomes, response times, and confidence ratings compared to models based on overall value alone. Our results provide important evidence that incorporating attribute-level information into computational models helps us to better understand the cognitive processes involved in value-based decision- making.
Transduction mechanisms for cold temperature in mouse trigeminal and vagal ganglion neurons innervating different peripheral organs
Authors: Gers-Barlag Katharina , Hernández-Ortego Pablo , Quintero Eva , Viana Félix
Published: August 2021

Thermal signals are critical elements in the operation of interoceptive and exteroceptive neural circuits, essential for triggering thermally-driven reflexes and conscious behaviors. A fraction of cutaneous and visceral sensory endings are activated by cold temperatures. Compared to somatic (DRG and TG) neurons, little is known about the mechanisms underlying cold sensitivity of visceral vagal neurons. We used molecular, pharmacological and genetic tools for a side-by-side characterization of cold-sensitive (CS) neurons in adult mouse trigeminal (TG) and vagal ganglia (VG).

We found that CS neurons are larger in size and more abundant in VG than in TG. In VG, the majority of CS neurons co-express TRPA1 markers and cold-evoked responses are severely blunted inTrpa1KO mice. Cold sensitivity was evident in neurons with the highest TRPA1 expression. In contrast, TRPM8 deletion or pharmacological TRPM8 blockade had little impact on VG cold sensitivity. Consistent with these findings, inTrpm8eYFPreporter mice we found limited expression of TRPM8 in VG and restricted to the rostral jugular ganglion.In vivoretrograde labelling of airway-innervating vagal neurons demonstrated their enhanced cold sensitivity and a higher expression of TRPA1 compared to neurons innervating the stomach wall.

In contrast, the majority of CS TG neurons co-express TRPM8 markers and their cold sensitivity is reduced after TRPM8 deletion or blockade. However, pharmacological or genetic reduction of TRPA1 showed that these channels contribute significantly to high-threshold cold sensitivity in TG, suggestive of a role in noxious cold sensing. In both ganglia, a fraction of CS neurons responded to cooling by a mechanism independent of TRPA1 or TRPM8 yet to be characterized.

Finally, in both ganglia, sensitivity to cold varied widely and was enhanced by the potassium channel blocker 4-AP. This effect was independent of the cold sensor expressed by the neuron, suggestive of a common excitability brake mechanism.

Significance statement

Temperature sensing and its regulation is a critical homeostatic function. Little is known about the molecular mechanism of cold sensing by visceral sensory endings and their relative weight in different visceral organs. This study highlights important differences in thermotransduction mechanisms between somatic (trigeminal) and visceral (vagal) primary sensory neurons, establishing a critical role of TRPA1 channels in visceral cold transduction. The study describes quantitative differences in cold sensitivity of visceral neurons innervating the stomach and the lower airways, suggesting that cold transduction mechanisms may be fine-tuned to the specific needs of different organs. This study significantly advances our understanding of cold sensing in trigeminal and vagal neurons and reveals distinct drug targets for the pharmacological modulation of these thermoreceptors.