bluuebunny/crossref_metadata_2025 huggingface dataset:
Narrow Leaf21, encoding ribosomal protein RPS3A, controls leaf development in rice
Authors: Uzair Muhammad , Long Haixin , Zafar Syed Adeel , Patil Suyash B , Chun Yan , Li Lu , Fang Jingjing , Zhao Jinfeng , Peng Lixiang , Yuan Shoujiang , Li Xueyong
Published: February 2021

Leaf morphology influences photosynthesis, transpiration, and ultimately crop yield. However, the molecular mechanism of leaf development is still not fully understood. Here, we identified and characterized the narrow leaf21 (nal21) mutant in rice (Oryza sativa), showing a significant reduction in leaf width, leaf length and plant height, and increased tiller number. Microscopic observation revealed defects in the vascular system and reduced epidermal cell size and number in the nal21 leaf blade. Map-based cloning revealed that NAL21 encodes a ribosomal small subunit protein RPS3A. Ribosome-targeting antibiotics resistance assay and ribosome profiling showed a significant reduction in the free 40S ribosome subunit in the nal21 mutant. The nal21 mutant showed aberrant auxin responses in which multiple auxin response factors (ARFs) harboring upstream open-reading frames (uORFs) in their 5′-untranslated region were repressed at the translational level. The WUSCHEL-related homeobox 3A (OsWOX3A) gene, a key transcription factor involved in leaf blade lateral outgrowth, is also under the translational regulation by RPS3A. Transformation with modified OsARF11, OsARF16, and OsWOX3A genomic DNA (gDNA) lacking uORFs rescued the narrow leaf phenotype of nal21 to a better extent than transformation with their native gDNA, implying that RPS3A could regulate translation of ARFs and WOX3A through uORFs. Our results demonstrate that proper translational regulation of key factors involved in leaf development is essential to maintain normal leaf morphology.
Who Identifies as “Latinx”? The Generational Politics of Ethnoracial Labels
Authors: Mora G Cristina , Perez Reuben , Vargas Nicholas
Published: February 2021

Over the past 5 years, the “Latinx” label has become increasingly popular within academia, politics, and social media. Yet, little is known about who has adopted the term at this relatively early stage and how it might be interpreted. Drawing on a unique data set of US-born Californians, as well as Latina/o/x Studies insight, this paper provides the first academic survey results on “Latinx” identification. We find that close to 25 percent of respondents identify with the term regularly, and that its early adoption varies across groups. Specifically, political ideology, especially progressive politics, is strongly correlated with use of the label. We also find that both immigrant generation and birth cohort matter considerably, with second generation immigrants and people born in Generation Z (since 1995) most likely to identify with the term. Finally, our findings show that “Latinx” is largely understood as complementary to, not mutually exclusive of, other panethnic labels like “Hispanic” and “Latino.” Taken together, our results suggest that generational politics matter for understanding early label diffusion and that Latinos adopt a variety of panethnic labels that they likely use in different contexts. We discuss these findings in terms of our broader understanding of Latinidad, racialization, and the symbolic power of ethnoracial labels.
No evidence for intra-individual correlations between sleep-mediated declarative memory consolidation and slow-wave sleep
Authors: Cordi Maren Jasmin , Rasch Björn
Published: February 2021

Study Objectives

Memory consolidation benefits from a retention period filled with sleep. Several theoretical accounts assume that slow-wave sleep (SWS) contributes functionally to processes underlying the stabilization of declarative memories during sleep. However, reports on correlations between memory retention and the amount of SWS are mixed and typically rely on between-subject correlations and small sample sizes. Here we tested for the first time whether the amount of SWS during sleep predicts the effect of sleep on memory consolidation on an intra-individual level in a large sample.

Methods

One hundred and fifty-nine healthy participants came to the lab twice and took a 90 min nap in both sessions. Sleep-mediated memory benefits were tested using the paired associates word-learning task in both sessions.

Results

In contrast to the theoretical prediction, intra-individual differences in sleep-mediated memory benefits did not significantly correlate with differences in SWS or SWA between the two naps. Also between subjects, the amount of SWS did not correlate with memory retention across the nap. However, subjective ratings of sleep quality were significantly associated with the amount of SWS.

Conclusion

Our results question the notion that the amount of SWS per se is functionally related to processes of memory consolidation during sleep. While our results do not exclude an important role of SWS for memory, they suggest that “more SWS” does not necessarily imply better memory consolidation.
Characterization of Virulence Phenotypes of Heterodera glycines in Heilongjiang, Northeast China
Authors: Chen Jingsheng , Zhou Yuanyuan , Wang Yuanyuan , Fan Haiyan , Liu Xiaoyu , Wang Dong , Zhao Di , Duan Yuxi , Zhu Xiaofeng , Chen Lijie
Published: February 2021

Knowledge about virulent phenotypes of Heterodera glycines Ichinohe, 1952 (soybean cyst nematode, SCN) is essential for breeding resistant cultivars and managing this nematode. Heilongjiang Province is the major soybean-producing region in China. SCN has been reported in 63 regions in Heilongjiang Province. To determine the prevalence and virulence of phenotypes of SCN, 112 soil samples were collected from soybean fields throughout the province in 2015. SCN was detected in 62 (55.4%) of these samples, with population densities ranging from 150 to 41,750 eggs and juveniles per 100 cm3 of soil. Eleven HG types, namely HG 0, 1.2.3.5.7, 1.2.3.7, 1.3.4.7, 1.3.7, 2, 2.5.7, 2.7, 6, 6.7, and 7, were detected. The percentages of SCN populations with female indices greater than 10 ranged from 4.8% for PI 437654 to 64.5% for PI 548316. This is the first report of seven of the HG types from Heilongjiang. These results provide guidance for breeding efforts and control strategies to combat SCN.
Influence of the Environment and Vegetable Cropping Systems on Plant-Parasitic Nematode Communities in Southern Georgia
Authors: Marquez Josiah , Severns Paul M. , Hajihassani Abolfazl
Published: February 2021

Plant-parasitic nematodes (PPN) limit yields of vegetable production in the United States. During the spring and fall cropping seasons of 2018, 436 fields in bare ground and plastic bed cropping systems were randomly sampled from 29 counties in southern Georgia. The incidence (%), mean relative abundance, and maximum relative abundance (nematodes per 100 cm3 of soil) of the 10 different PPN genera detected in 32 vegetable crops in bare ground and plastic bed cropping systems include Meloidogyne spp. (67.3%; mean, 292; maximum, 14,144), Nanidorus spp. (49.4%; mean, 6; maximum, 136), Mesocriconema spp. (39.6%; mean, 17; maximum, 340), Helicotylenchus spp. (31.6%; mean, 20; maximum, 1152), Pratylenchus spp. (20.1%; mean, 2; maximum, 398), Rotylenchulus spp. (5.9%; mean, 1; maximum, 116), Hoplolaimus spp. (12.6%; mean, 1; maximum, 78), Heterodera spp. (2.3%; mean, <1; maximum, 60), Tylenchorhynchus spp. (0.9%; mean, <1; maximum, 12), and Xiphinema spp. (0.2%; mean, <1; maximum, 2). A nonmetric multidimensional scaling analysis indicated that most environmental and geological factors (i.e., longitude, precipitation, soil moisture, sand and silt content, and soil electrical conductivity) had no apparent relationship with nematode counts, except for latitude, soil pH, and temperature. The multirank permutation procedure followed by indicator species analysis and nonparametric Kruskal–Wallis analysis of variance indicated that Meloidogyne spp. are the predominant PPN associated with plastic beds in the south region sampled. The south region consisted mainly of commercial fields that rotated multiple vegetables crops through the same plastic beds. All other PPNs were associated with bare ground beds in the north region that are commonly rotated with row crops. This study validates that Meloidogyne spp. are the most important PPN in vegetable fields of southern Georgia and suggests that cropping systems have a greater effect on PPN population dynamics than the environment.
Opportunities and challenges for machine learning in weather and climate modelling: hard, medium and soft AI
Authors: Chantry Matthew , Christensen Hannah , Dueben Peter , Palmer Tim
Published: February 2021

In September 2019, a workshop was held to highlight the growing area of applying machine learning techniques to improve weather and climate prediction. In this introductory piece, we outline the motivations, opportunities and challenges ahead in this exciting avenue of research.

This article is part of the theme issue ‘Machine learning for weather and climate modelling’.
Climbing down Charney’s ladder: machine learning and the post-Dennard era of computational climate science
Authors: Balaji V.
Published: February 2021

The advent of digital computing in the 1950s sparked a revolution in the science of weather and climate. Meteorology, long based on extrapolating patterns in space and time, gave way to computational methods in a decade of advances in numerical weather forecasting. Those same methods also gave rise to computational climate science, studying the behaviour of those same numerical equations over intervals much longer than weather events, and changes in external boundary conditions. Several subsequent decades of exponential growth in computational power have brought us to the present day, where models ever grow in resolution and complexity, capable of mastery of many small-scale phenomena with global repercussions, and ever more intricate feedbacks in the Earth system. The current juncture in computing, seven decades later, heralds an end to what is called Dennard scaling, the physics behind ever smaller computational units and ever faster arithmetic. This is prompting a fundamental change in our approach to the simulation of weather and climate, potentially as revolutionary as that wrought by John von Neumann in the 1950s. One approach could return us to an earlier era of pattern recognition and extrapolation, this time aided by computational power. Another approach could lead us to insights that continue to be expressed in mathematical equations. In either approach, or any synthesis of those, it is clearly no longer the steady march of the last few decades, continuing to add detail to ever more elaborate models. In this prospectus, we attempt to show the outlines of how this may unfold in the coming decades, a new harnessing of physical knowledge, computation and data.

This article is part of the theme issue ‘Machine learning for weather and climate modelling’.
Towards implementing artificial intelligence post-processing in weather and climate: proposed actions from the Oxford 2019 workshop
Authors: Haupt Sue Ellen , Chapman William , Adams Samantha V. , Kirkwood Charlie , Hosking J. Scott , Robinson Niall H. , Lerch Sebastian , Subramanian Aneesh C.
Published: February 2021

The most mature aspect of applying artificial intelligence (AI)/machine learning (ML) to problems in the atmospheric sciences is likely post-processing of model output. This article provides some history and current state of the science of post-processing with AI for weather and climate models. Deriving from the discussion at the 2019 Oxford workshop on Machine Learning for Weather and Climate, this paper also presents thoughts on medium-term goals to advance such use of AI, which include assuring that algorithms are trustworthy and interpretable, adherence to FAIR data practices to promote usability, and development of techniques that leverage our physical knowledge of the atmosphere. The coauthors propose several actionable items and have initiated one of those: a repository for datasets from various real weather and climate problems that can be addressed using AI. Five such datasets are presented and permanently archived, together with Jupyter notebooks to process them and assess the results in comparison with a baseline technique. The coauthors invite the readers to test their own algorithms in comparison with the baseline and to archive their results.

This article is part of the theme issue ‘Machine learning for weather and climate modelling’.
Domain-driven models yield better predictions at lower cost than reservoir computers in Lorenz systems
Authors: Pyle Ryan , Jovanovic Nikola , Subramanian Devika , Palem Krishna V. , Patel Ankit B.
Published: February 2021

Recent advances in computing algorithms and hardware have rekindled interest in developing high-accuracy, low-costsurrogatemodels for simulating physical systems. The idea is to replace expensive numerical integration of complex coupled partial differential equations at fine time scales performed on supercomputers, with machine-learned surrogates that efficiently and accurately forecast future system states using data sampled from the underlying system. One particularly popular technique being explored within the weather and climate modelling community is theecho state network(ESN), an attractive alternative to other well-known deep learning architectures. Using the classical Lorenz 63 system, and the three tier multi-scale Lorenz 96 system (Thornes T, Duben P, Palmer T. 2017Q. J. R. Meteorol. Soc.143, 897–908. (doi:10.1002/qj.2974)) as benchmarks, we realize that previously studied state-of-the-art ESNs operate in two distinct regimes, corresponding to low and high spectral radius (LSR/HSR) for the sparse, randomly generated, reservoir recurrence matrix. Using knowledge of the mathematical structure of the Lorenz systems along with systematic ablation and hyperparameter sensitivity analyses, we show that state-of-the-art LSR-ESNs reduce to a polynomial regression model which we call Domain-Driven Regularized Regression (D2R2). Interestingly, D2R2 is a generalization of the well-known SINDy algorithm (Brunton SL, Proctor JL, Kutz JN. 2016Proc. Natl Acad. Sci. USA113, 3932–3937. (doi:10.1073/pnas.1517384113)). We also show experimentally that LSR-ESNs (Chattopadhyay A, Hassanzadeh P, Subramanian D. 2019 (http://arxiv.org/abs/1906.08829)) outperform HSR ESNs (Pathak J, Hunt B, Girvan M, Lu Z, Ott E. 2018Phys. Rev. Lett.120, 024102. (doi:10.1103/PhysRevLett.120.024102)) while D2R2 dominates both approaches. A significant goal in constructing surrogates is to cope with barriers to scaling in weather prediction and simulation of dynamical systems that are imposed by time and energy consumption in supercomputers.Inexact computinghas emerged as a novel approach to helping with scaling. In this paper, we evaluate the performance of three models (LSR-ESN, HSR-ESN and D2R2) by varying the precision or word size of the computation as our inexactness-controlling parameter. For precisions of 64, 32 and 16 bits, we show that, surprisingly, the least expensive D2R2 method yields the most robust results and the greatest savings compared to ESNs. Specifically, D2R2 achieves 68 × in computational savings, with an additional 2 × if precision reductions are also employed, outperforming ESN variants by a large margin.

This article is part of the theme issue ‘Machine learning for weather and climate modelling’.
The genetic code is not optimized for resource conservation
Authors: Xu Haiqing , Zhang Jianzhi
Published: February 2021

Shenhav and Zeevi conclude in a recent article (Science370:683-687) that the universal genetic code (UGC) is optimized for resource conservation because mutations are less likely to increase proteomic nitrogen and carbon uses under the UGC than under random genetic codes (RGCs). Their finding results from miscalculating mutational effects and benchmarking against biased RGCs. Our reanalysis refutes their conclusion.
Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19
Authors: Feyaerts Dorien , Hédou Julien , Gillard Joshua , Chen Han , Tsai Eileen S. , Peterson Laura S. , Ando Kazuo , Manohar Monali , Do Evan , Dhondalay Gopal K.R. , Fitzpatrick Jessica , Artandi Maja , Chang Iris , Snow Theo T. , Chinthrajah R. Sharon , Warren Christopher M. , Wittman Rich , Meyerowitz Justin G. , Ganio Edward A. , Stelzer Ina A. , Han Xiaoyuan , Verdonk Franck , Gaudillière Dyani K. , Mukherjee Nilanjan , Tsai Amy S. , Rumer Kristen K. , Jiang Sizun , Ferrer Sergio Iván Valdés , Kelly J. Daniel , Furman David , Aghaeepour Nima , Angst Martin S. , Boyd Scott D. , Pinsky Benjamin A. , Nolan Garry P. , Nadeau Kari C. , Gaudillière Brice , McIlwain David R.
Published: February 2021

The biological determinants of the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, basal signaling activity, and signaling responses to inflammatory ligands were assessed in peripheral blood from patients with mild, moderate, and severe COVID-19, at the time of diagnosis. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identified and independently validated a multivariate model classifying COVID-19 severity (multi-class AUCtraining= 0.799, p-value = 4.2e-6; multi-class AUCvalidation= 0.773, p-value = 7.7e-6). Features of this high-dimensional model recapitulated recent COVID-19 related observations of immune perturbations, and revealed novel biological signatures of severity, including the mobilization of elements of the renin-angiotensin system and primary hemostasis, as well as dysregulation of JAK/STAT, MAPK/mTOR, and NF-κB immune signaling networks. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for the prevention of COVID-19 progression.

Feyaerts et al. demonstrate that an integrated analysis of plasma and single-cell proteomics differentiates COVID-19 severity and reveals severity-specific biological signatures associated with the dysregulation of the JAK/STAT, MAPK/mTOR, and NF-κB immune signaling networks and the mobilization of the renin-angiotensin and hemostasis systems.
An analysis of school absences in England during the Covid-19 pandemic
Authors: Southall Emma , Holmes Alex , Hill Edward M. , Atkins Benjamin D. , Leng Trystan , Thompson Robin N. , Dyson Louise , Keeling Matt J. , Tildesley Michael J.
Published: February 2021

The introduction of SARS-CoV-2, the virus that causes COVID-19 infection, in the UK in early 2020, resulted in the UK government introducing several control policies in order to reduce the spread of disease. As part of these restrictions, schools were closed to all pupils in March (except for vulnerable and key worker children), before re-opening to certain year groups in June. Finally all school children returned to the classroom in September. In this paper, we analyse the data on school absences from September 2020 to December 2020 as a result of COVID-19 infection and how that varied through time as other measures in the community were introduced. We utilise data from the Educational Settings database compiled by the Department for Education and examine how pupil and teacher absences change in both primary and secondary schools.

Our results show that absences as a result of COVID-19 infection rose steadily following the re-opening of schools in September. Cases in teachers were seen to decline during the November lockdown, particularly in those regions that had previously been in tier 3, the highest level of control at the time. Cases in secondary school pupils increased for the first two weeks of the November lockdown, before decreasing. Since the introduction of the tier system, the number of absences owing to confirmed infection in primary schools was observed to be significantly lower than in secondary schools across all regions and tiers.

In December, we observed a large rise in the number of absences per school in secondary school settings in the South East and Greater London, but such rises were not observed in other regions or in primary school settings. We conjecture that the increased transmissibility of the new variant in these regions may have contributed to this rise in cases in secondary schools. Finally, we observe a positive correlation between cases in the community and cases in schools in most regions, with weak evidence suggesting that cases in schools lag behind cases in the surrounding community. We conclude that there is not significant evidence to suggest that schools are playing a significant role in driving spread in the community and that careful monitoring may be required as schools re-open to determine the effect associated with open schools upon community incidence.
Cytokine response following perturbation of the cervicovaginal milieu during HPV genital infection
Authors: Selinger Christian , Rahmoun Massilva , Murall Carmen Lia , Bernat Claire , Boué Vanina , Bonneau Marine , Graf Christelle , Grasset Sophie , Groc Soraya , Reynes Jacques , Hirtz Christophe , Jacobs Nathalie , Alizon Samuel
Published: February 2021

Human papillomaviruses (HPVs) are the most oncogenic viruses known to human, causing nearly all cervical cancers worldwide. Highly prevalent in young, sexually active women, most HPV infections are cleared within 3 years, and only a minority of those infections persist and lead to cancer later in life. To better characterize the immuno-modulatory impact of early HPV infection and more generally perturbations of the cervicovaginal milieu, we measured changes in a panel of 20 cytokines, known as highly dynamic effector molecules implicated in cell signaling. We analyzed 92 cervicovaginal samples collected from young, sexually active women who were tested for or diagnosed with HPV, chlamydia, and bacterial vaginosis. Also, symptoms associated with genital inflammation and infection were collected through self-reporting.

Following a parsimonious multi-factor modeling approach, our statistical analyses revealed that increased IL-1Alpha and IL-12/IL-23p40 concentrations were associated with HPV infection. Cytokine network analysis further highlighted the role of IL-1Alpha and macrophage inflammatory proteins (MIP-3Alpha) in HPV-associated immuno-modulation.
Exposure to per- and polyfluoroalkyl substances associates with altered lipid profile of breast milk
Authors: Lamichhane Santosh , Siljander Heli , Duberg Daniel , Honkanen Jarno , Virtanen Suvi M. , Orešič Matej , Knip Mikael , Hyötyläinen Tuulia
Published: February 2021

Background

Chemical composition of human breast milk is highly variable inter- and intra-individually. Environmental factors are suspected to partly explain the compositional variation, however, their impact on breast milk composition is currently poorly understood.

Objectives

We sought (1) to define the impact of maternal exposure to per- and polyfluoroalkyl substances (PFAS) on lipid composition of human breast milk, and (2) to study the combined impact of maternal PFAS exposure and breast milk lipid composition on the growth of the infants.

Methods

In a mother-infant study (n=44) we measured the levels of PFAS and lipids in maternal serum and conducted lipidomics analysis of breast milk at birth and at 3 months of infant age, by using ultra high performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry. Maternal diet was studied by a validated food frequency questionnaire.

Results

PFAS levels were inversely associated with total lipid levels in the breast milk collected at birth. In the high exposure group, the ratio of acylated saturated and polyunsaturated fatty acids in triacylglycerols was increased. Moreover, high exposure to PFAS associated with the altered phospholipid composition, which was indicative of unfavorable increase in the size of milk fat globules. These changes in the milk lipid composition were further associated with slower infant growth and with elevated intestinal inflammatory markers.

Discussion

Our data suggest that the maternal exposure to PFAS impacts the nutritional quality of the breast milk, which, in turn, may have detrimental impact on the health and growth of the children later in life.
A multi-phase multi-objective genome-scale model shows diverse redox balance strategies in yeasts
Authors: Henriques David , Minebois Romain , Mendoza Sebastian , Macías Laura G. , Pérez-Torrado Roberto , Barrio Eladio , Teusink Bas , Querol Amparo , Balsa-Canto Eva
Published: February 2021

Yeasts constitute over 1500 species with great potential for biotechnology. Still, the yeastSaccharomyces cerevisiaedominates industrial applications and many alternative physiological capabilities of lesser-known yeasts are not being fully exploited. While comparative genomics receives substantial attention, little is known about yeasts’ metabolic specificity in batch cultures. Here we propose a multi-phase multi-objective dynamic genome-scale model of yeast batch cultures that describes the uptake of carbon and nitrogen sources and the production of primary and secondary metabolites. The model integrates a specific metabolic reconstruction, based on the consensus Yeast8, and a kinetic model describing the time-varying culture environment. Besides, we proposed a multi-phase multi-objective flux balance analysis to compute the dynamics of intracellular fluxes. We then compared the metabolism ofS. cerevisiaeandS. uvarumstrains in wine fermentation. The model successfully explained the experimental data and brought novel insights into how cryotolerant strains achieve redox balance. The proposed modeling captures the dynamics of metabolism throughout the batch and offers a systematic approach to prospect or engineer novel yeast cell factories.
Treatment of irritant contact dermatitis in healthcare settings during the COVID19 pandemic: The emollient Dermol 500 exhibits virucidal activity against influenza A virus and SARS-CoV-2
Authors: Styles Christine T. , Oever Michael Vanden , Brown Jonathan , Rai Sweta , Walsh Sarah , Ryan Finola M. , Barclay Wendy S. , Edgar Rachel S.
Published: February 2021

Objectives

To investigate whether the antimicrobial emollient Dermol 500 and its active components, benzalkonium chloride (BAK) and chlorhexidine dihydrochloride (CD), exhibit virucidal activity thus informing whether Dermol 500 is a suitable soap substitute for use during the COVID19 pandemic, to combat the increased incidence of work-related contact dermatitis in clinical settings that we report here.

Methods

Inactivation of influenza A virus and SARS-CoV-2 by Dermol 500 and the independent and combined virucidal activity of the Dermol 500 components BAK and CD was assessed by influenza A virus and SARS-CoV-2 infectivity assays. Viruses were treated with concentrations of BAK and CD comparable to Dermol 500, and lower, and infectivity of the viruses assessed by titration.

Results

Dermol 500 exhibits comparable virucidal activity to alcohol-based sanitisers against influenza A virus and SARS-CoV-2. In addition, the Dermol 500 components BAK and CD exhibit independent and synergistic virucidal activity against influenza A virus and SARS-CoV-2, the causative agent of COVID19.

Conclusions

The synergistic virucidal activity of the Dermol 500 components BAK and CD makes Dermol 500 suitable as a soap substitute to treat and prevent work-related contact dermatitis in healthcare settings.

KEY MESSAGES

What is already known about this subject?

Work-related contact dermatitis is a prominent issue among healthcare workers, and likely exacerbated by the enhanced hand hygiene and personal protective equipment required to control infection during the COVID19 pandemic.

The antimicrobial lotion Dermol 500 is frequently prescribed as an emollient and soap substitute to help prevent and treat dermatitis, but its use during the COVID19 pandemic was not advised as its capacity to inactivate viruses was unknown.

What are the new findings?

Increased incidence of irritant contact dermatitis was recorded amongst healthcare workers at King’s College Hospital NHS Foundation Trust in 2020 compared to 2019.

Dermol 500 lotion and its antimicrobial components, benzalkonium chloride (BAK) and chlorhexidine dihydrochloride (CD), exhibit virucidal activity against influenza A virus and SARS-CoV-2, the virus responsible for COVID19 pandemic.

How might this impact policy or clinical practice in the foreseeable future?

Our results demonstrate that Dermol 500 can be safely used as a soap substitute to treat work-related contact dermatitis in clinical care settings during the COVID19 pandemic.

Employers can meet their obligations under COSHH to eliminate workplace exposure to a harmful substance and substitute with an alternative product for hand hygiene.
Severe COVID-19 pneumonia and barotrauma: From the frying pan into the fire
Authors: Kalpakam Hariprasad , Bansal Sameer , Suresh Nithya , Kade Samson , Thorbole Anmol , Mehta Ravindra M
Published: February 2021

Aim

COVID-19 pneumonia with ARDS (C-ARDS) has a high mortality. Preliminary reports indicate a higher incidence of barotrauma in patients with C-ARDS[1] both on invasive mechanical ventilation (iMV) and non-invasive ventilation (NIV) This study examines the incidence and risk factors for barotrauma and change in outcomes after barotrauma in patients with severe C-ARDS on positive pressure respiratory support (PPRS).

Methods and materials

This is a retrospective study of C-ARDS associated barotrauma over 5 months in patients on PPRS in a tertiary COVID care center. The type of barotrauma, intervention, related factors, such as type of respiratory support (iMV vs NIV), airway pressure prior to the occurrence of barotrauma, and post-barotrauma outcomes were analyzed.

Results

A total of 38/410 (9.3%) C-ARDS patients on PPRS [mean age 57.82 ± 13.3 years, 32 males (84.2%)] developed barotrauma. Of these, 20 patients (52.6%) were on NIV and 18 (47.4%) patients were iMV on standard recommended settings. The median P/F ratio of patients on MV at the time of barotrauma was 116.4 (IQR 72.4, 193.25). The details of barotrauma were as follows: 24 patients had pneumothorax (PTX), 2 had pneumo-mediastinum and 12 had subcutaneous emphysema. Overall, 24/38 (63.2%) patients, including 15/18 (83.3%) on MV succumbed to their illness. The barotrauma happened a median of 6.5 days (IQR 4.75,13) after admission and 15 days (IQR 10.25,18.0) from symptom onset. The median duration from barotrauma to death was 7 days (IQR 2.25, 8.0) and barotrauma to discharge (for survivors) was 12.5 days (IQR 8.0, 21.25). All patients received steroids and 11/38 (28.9%) received additional immunosuppression with tocilizumab.

Conclusion

A high incidence of barotrauma was seen in this large series of severe C-ARDS patients on PPRS. Barotrauma led to further deterioration in the clinical status leading to a fatal outcome in the majority of the MV patients, despite prompt treatment.
Patient and physician shared decision making behaviors in oncology: Evidence on adequate measurement properties of the iSHARE questionnaires
Authors: Bomhof-Roordink Hanna , Stiggelbout Anne M. , Gärtner Fania R. , Portielje Johanneke E.A. , de Kroon Cor D. , Peeters Koen C.M.J. , Neelis Karen J. , Dekker Jan Willem T. , van der Weijden Trudy , Pieterse Arwen H. ,   for the iSHARE study group
Published: February 2021

Objectives

We have developed two questionnaires to assess the shared decision making (SDM) process in oncology; the iSHAREpatient and iSHAREphysician. In this study, we aimed to determine: scores, construct validity, test-retest agreement (iSHAREpatient), and inter-rater (iSHAREpatient-iSHAREphysician) agreement.

Methods

Physicians from seven Dutch hospitals recruited cancer patients, and completed the iSHAREphysician and SDM-Questionnaire–physician version. Their patients completed the: iSHAREpatient, 9-item SDM-Questionnaire, Decisional Conflict Scale, Combined Outcome Measure for Risk communication And treatment Decision making Effectiveness, and Perceived Efficacy in Patient-Physician Interactions. We formulated, respectively, one (iSHAREphysician) and 10 (iSHAREpatient) a priori hypotheses regarding correlations between the iSHARE questionnaires and questionnaires assessing related constructs. To assess test-retest agreement patients completed the iSHAREpatient again 1-2 weeks later.

Results

In total, 151 treatment decision making processes with unique patients were rated. Dimension and total iSHARE scores were high both in patients and physicians. The hypothesis on the iSHAREphysician and 9/10 hypotheses on the iSHAREpatient were confirmed. Test-retest and inter-rater agreement were >.60 for most items.

Conclusions

The iSHARE questionnaires show high scores, have good construct validity, substantial test-retest agreement, and moderate inter-rater agreement.

Practice implications

Results from the iSHARE questionnaires can inform both physician- and patient-directed efforts to improve SDM in clinical practice.
SARS-CoV-2 incidence and risk factors in a national, community-based prospective cohort of U.S. adults
Authors: Nash Denis , Rane Madhura S. , Chang Mindy , Kulkarni Sarah Gorrell , Zimba Rebecca , You William , Berry Amanda , Mirzayi Chloe , Kochhar Shivani , Maroko Andrew , Robertson McKaylee M. , Westmoreland Drew A. , Parcesepe Angela M. , Waldron Levi , Grov Christian
Published: February 2021

Background

Epidemiologic risk factors for incident SARS-CoV-2 infection as determined via prospective cohort studies greatly augment and complement information from case-based surveillance and cross-sectional seroprevalence surveys.

Methods

We estimated the incidence of SARS-CoV-2 infection and risk factors in a well-characterized, national prospective cohort of 6,738 U.S. adults, enrolled March-August 2020, a subset of whom (n=4,510) underwent repeat serologic testing between May 2020 and January 2021. We examined the crude associations of sociodemographic factors, epidemiologic risk factors, and county-level community transmission with the incidence of seroconversion. In multivariable Poisson models we examined the association of social distancing and a composite score of several epidemiologic risk factors with the rate of seroconversion.

Findings

Among the 4,510 individuals with at least one serologic test, 323 (7.3%, 95% confidence interval [CI] 6.5%-8.1%) seroconverted by January 2021. Among 3,422 participants seronegative in May-September 2020 and tested during November 2020-January 2021, we observed 161 seroconversions over 1,646 person-years of follow-up (incidence rate of 9.8 per 100 person-years [95%CI 8.3-11.5]). In adjusted models, participants who reported always or sometimes social distancing with people they knew (IRRalways vs. never0.43, 95%CI 0.21-1.0; IRRsometimes vs. never0.47, 95%CI 0.22-1.2) and people they did not know (IRRalways vs. never0.64, 95%CI 0.39-1.1; IRRsometimes vs. never0.60, 95%CI 0.38-0.97) had lower rates of seroconversion. The rate of seroconversion increased across tertiles of the composite score of epidemiologic risk (IRRmedium vs. low1.5, 95%CI 0.92-2.4; IRRhigh vs. low3.0, 95%CI 2.0-4.6). Among the 161 observed seroconversions, 28% reported no symptoms of COVID-like illness (i.e., were asymptomatic), and 27% reported a positive SARS-CoV-2 diagnostic test. Ultimately, only 29% reported isolating and 19% were asked about contacts.

Interpretation

Modifiable epidemiologic risk factors and poor reach of public health strategies drove SARS-CoV-2 transmission across the U.S during May 2020-January 2021.

Funding

U.S. National Institutes of Allergy and Infectious Diseases (NIAID).
Differentially accessible Cdc4 phospho-degrons regulate Ctf19CCANkinetochore subunit stability in mitosis
Authors: Böhm Miriam , Killinger Kerstin , Dudziak Alexander , Pant Pradeep , Jänen Karolin , Hohoff Simone , Mechtler Karl , Örd Mihkel , Loog Mart , Sanchez-Garcia Elsa , Westermann Stefan
Published: February 2021

Kinetochores are multi-subunit protein assemblies that link chromosomes to microtubules of the mitotic and meiotic spindle. How effective, yet strictly centromere-dependent kinetochore assembly is coupled to cell cycle progression is incompletely understood. Here, by combining comprehensive phosphorylation analysis of native Ctf19CCANsubunits with biochemical and functional assays in the model system budding yeast, we demonstrate that Cdk1 phosphorylation activates phospho-degrons on the essential subunit Ame1CENP-Uwhich are recognized by the E3 ubiquitin ligase complex SCF-Cdc4. Gradual phosphorylation of degron motifs culminates in M-Phase and targets the protein for degradation. Binding of the Mtw1 complex shields the proximal phospho-degron, protecting kinetochore-bound Ame1 from the degradation machinery. Artificially increasing degron strength partially suppresses the temperature-sensitivity of acdc4mutant, while overexpression of Ame1-Okp1 is toxic to cells, demonstrating the physiological importance of this mechanism. We propose that phospho-regulated clearance of excess CCAN subunits protects against ectopic kinetochore assembly and contributes to mitotic checkpoint silencing. Our results suggest a novel strategy for how phospho-degrons can be used to regulate the assembly of multi-subunit complexes.
Transcriptional and translational responsiveness of theNeisseria gonorrhoeaetype IV secretion system to conditions of host infections
Authors: Callaghan Melanie M. , Klimowicz Amy K. , Shockey Abigail C. , Kane John , Pepperell Caitlin S. , Dillard Joseph P.
Published: February 2021

The type IV secretion system ofNeisseria gonorrhoeaetranslocates single-stranded DNA into the extracellular space, facilitating horizontal gene transfer and initiating biofilm formation. Expression of this system has been observed to be low under laboratory conditions, and multiple levels of regulation have been identified. We used a translational fusion oflacZtotraD, the gene for the type IV secretion system coupling protein, to screen for increased type IV secretion system expression. We identified several physiologically relevant conditions, including surface adherence, decreased manganese or iron, and increased zinc or copper, which increase gonococcal type IV secretion system protein levels through transcriptional and/or translational mechanisms. These metal treatments are reminiscent of the conditions in the macrophage phagosome. The ferric uptake regulator, Fur, was found to represstraDtranscript levels, but to also have a second role, acting to allow TraD protein levels to increase only in the absence of iron. To better understand type IV secretion system regulation during infection, we examined transcriptomic data from active urethral infection samples from five men. These data demonstrated differential expression of 20 of 21 type IV secretion system genes during infection, indicating upregulation of genes necessary for DNA secretion during host infection.
Cerebrospinal fluid hemoglobin drives subarachnoid hemorrhage-related secondary brain injury
Authors: Akeret Kevin , Buzzi Raphael M. , Schaer Christian A. , Thomson Bart R. , Vallelian Florence , Wang Sophie , Willms Jan , Sebök Martina , Held Ulrike , Deuel Jeremy W. , Humar Rok , Regli Luca , Keller Emanuela , Hugelshofer Michael , Schaer Dominik J.
Published: February 2021

Secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH-SBI) is a significant contributor to poor outcomes in patients after rupture of an intracranial aneurysm. The lack of diagnostic biomarkers and novel drug targets represent an unmet need. Prior experimental evidence has suggested cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) as a pathophysiological driver of SAH-SBI. The aim of this study was to investigate the clinical and pathophysiological association between CSF-Hb and SAH-SBI. We prospectively enrolled 47 consecutive patients and collected daily CSF samples within 14 days after aneurysm rupture. There was very strong evidence for a positive association between CSF-Hb and SAH-SBI. The diagnostic accuracy of CSF-Hb for SAH-SBI markedly exceeded that of established methods (area under the curve: 0.89 [0.85-0.92]). Temporal LC-MS/MS CSF proteomics demonstrated that erythrolysis accompanied by an adaptive macrophage response are the two dominant biological processes occurring in the CSF space after aneurysm rupture. To further investigate the pathophysiology between CSF-Hb and SAH-SBI, we explored the vasoconstrictive and lipid peroxidation activities of Hb ex-vivo. These experiments revealed critical inflection points overlapping CSF-Hb concentration thresholds in patients with SAH-SBI. Selective Hb depletion and in-solution neutralization by the Hb-scavenger haptoglobin or the heme-scavenger hemopexin efficiently attenuated the vasoconstrictive and lipid peroxidation activities of CSF-Hb in patient CSF. Collectively, the clinical association between high CSF-Hb levels and SAH-SBI, the underlying pathophysiological rationale, and the favorable effects of haptoglobin and hemopexin in ex-vivo experiments position CSF-Hb as a highly attractive biomarker and potential drug target.
Biological attributes of age and gender variations in Indian COVID-19 cases: A retrospective data analysis
Authors: Kushwaha Savitesh , Khanna Poonam , Rajagopal Vineeth , Kiran Tanvi
Published: February 2021

Background

The associated risk factors, co-morbid conditions and biological variations varying with gender and age might be the cause of higher COVID-19 infection and deaths among males and older persons. The objective of this study was to predict and specify the biological attributes of variation in age and gender-based on COVID-19 status (deceased/recovered).

Methods

In this retrospective study, the data was extracted from a recognised web-based portal. A total of 112,860 patients’ record was filtered out and an additional 9,131 records were separately analyzed to examine age and gender relationship with patient’s COVID-19 status (recovered/deceased). Chi-square, t-test, binary logistic regression, and longitudinal regression analysis were conducted.

Results

The male COVID-19 cases (65.39%) were more than females (34.61%) and mean age of infected and recovered patients was 39.47±17.59 years and 36.85±18.51 years respectively. The odds for infection was significantly higher among females for lower age categories, which declines with age. The age-adjusted odds for recovery were significantly higher among females (O.R.=1.779) and odds for recovery was highest in 5-17 years age category (O.R.=88.286) independent of gender.

Conclusion

The chances of being COVID-19 infected was higher for females of lower age categories (<35 years) which decreases with age. The odds for recovery among females was significantly higher than males. The chances of recovery declines with increasing age and the variation could be attributed to the biological differences between age categories and gender.
Mortality from injury, overdose and suicide during the 2020 COVID-19
pandemic, March-July, 2020
Authors: Faust Jeremy S. , Du Chengan , Mayes Katherine Dickerson , Li Shu-Xia , Lin Zhenqiu , Barnett Michael L. , Krumholz Harlan M.
Published: February 2021

Introduction

The COVID-19 pandemic has been associated with substantial rates of
all-cause excess mortality. The contribution of external causes of death to
excess mortality including drug overdose, homicide, suicide, and
unintentional injuries during the initial outbreak in the United States is
less well documented.

Methods

Using public data published by the National Center for Health Statistics
on February 10, 2021, we measured monthly excess mortality (the gap between
observed and expected deaths) from five external causes using national-level
data published by National Center for Health Statistics; assault (homicide);
intentional self-harm (suicide); accidents (unintentional injuries); and
motor vehicle accidents. We used seasonal autoregressive integrated moving
average (sARIMA) models developed with cause-specific monthly mortality
counts and US population data from 2015-2019 and estimated the contribution
of individual cause-specific mortality to all-cause excess mortality from
March-July 2020.

Results

From March-July, 2020, 212,825 (95% CI 136,236-290,776) all-cause excess
deaths occurred in the US). There were 8,540 excess drug overdoses (all
intents) (95% CI 5,106 to 11,975), accounting for 4% of all excess
mortality; 1,455 excess homicide deaths (95% CI 708 to 2202, accounting for
0.7% of excess mortality; 5,492 excess deaths due to unintentional accidents
occurred (95% CI 85 to 10,899, accounting for 2.6% of excess mortality.
Though a non-significantly 135 (95% CI -1361 to 1,630) more MVA deaths were
recorded during the study period, a significant decrease in April (525; 95%
CI -817 to -233) and significant increases in June-July (965; 95% CI 348 to
1,587) were observed. Suicide deaths were statistically lower than projected
by 2,067 (95% CI 941-3,193 fewer deaths).

Meaning

Excess deaths from drug overdoses, homicide, and addicents occurred
during the pandemic but represented a small fraction of all-cause excess
mortality. The excess external causes of death, however, still represent
thousands of lives lost. Notably, deaths from suicide were lower than
expected and therefore did not contribute to excess mortality.
Digital technologies for monitoring and improving treatment adherence in children and adolescents with asthma: A scoping review of randomised controlled trials
Authors: Milne-Ives Madison , Meinert Edward
Published: February 2021

Background

Inadequate paediatric asthma care has resulted in potentially avoidable unplanned hospital admissions and morbidity. A wide variety of digital technologies have been developed to help monitor and support treatment adherence for children and adolescents with asthma. However, existing reviews need to be updated and expanded to provide an overview of the current state of research around these technologies and how they are being integrated into existing healthcare services and care pathways.

Objective

The purpose of this scoping review is to provide an overview of the current research landscape and knowledge gaps regarding the use of digital technologies to support the care of children and adolescents with asthma.

Methods

The review was structured according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and Population, Intervention, Comparator, Outcome, and Study (PICOS) frameworks. Five databases (PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, EMBASE, and PsycINFO) were systematically searched for studies published in English from 2014 on. One reviewer screened references, selected studies for inclusion based on the eligibility criteria, and extracted the data, which were synthesised in a descriptive analysis.

Results

A wide variety in study characteristics - including the number and age of participants, study duration, and type of digital intervention - was identified. There was mixed evidence for the effectiveness of the interventions; 6 of the 9 studies that evaluated treatment adherence found improvements, but the evidence was inconsistent for asthma control (4/9 found no evidence of effectiveness, and only one found significant evidence) and health outcome variables (4/7 found no evidence of effectiveness). The 5 studies that examined patient perceptions and assessments of acceptability and usability had generally positive findings.

Conclusions

Despite the range of different digital interventions being developed to support the monitoring and treatment adherence of children and adolescents with asthma, there is limited evidence to suggest that they achieve their range of intended outcomes. Stronger evidence of their effectiveness at achieving their specific aims is needed, as this will support decisions and research about their cost-effectiveness and how these technologies can best integrate with existing clinical care pathways. This research is necessary to determine which interventions are worth supporting and adopting in the clinical care pathways.