bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel polyadenylylation-dependent neutralization mechanism of the HEPN/MNT toxin/antitoxin system
Authors: Yao Jianyun , Zhen Xiangkai , Tang Kaihao , Liu Tianlang , Xu Xiaolong , Chen Zhe , Guo Yunxue , Liu Xiaoxiao , Wood Thomas K , Ouyang Songying , Wang Xiaoxue
Published: September 2020

The two-gene module HEPN/MNT is predicted to be the most abundant toxin/antitoxin (TA) system in prokaryotes. However, its physiological function and neutralization mechanism remains obscure. Here, we discovered that the MntA antitoxin (MNT-domain protein) acts as an adenylyltransferase and chemically modifies the HepT toxin (HEPN-domain protein) to block its toxicity as an RNase. Biochemical and structural studies revealed that MntA mediates the transfer of three AMPs to a tyrosine residue next to the RNase domain of HepT in Shewanella oneidensis. Furthermore, in vitro enzymatic assays showed that the three AMPs are transferred to HepT by MntA consecutively with ATP serving as the substrate, and this polyadenylylation is crucial for reducing HepT toxicity. Additionally, the GSX10DXD motif, which is conserved among MntA proteins, is the key active motif for polyadenylylating and neutralizing HepT. Thus, HepT/MntA represents a new type of TA system, and the polyadenylylation-dependent TA neutralization mechanism is prevalent in bacteria and archaea.
Associations Between Physical Therapy Visits and Pain and Physical Function After Knee Arthroplasty: A Cross-Lagged Panel Analysis of People Who Catastrophize About Pain Prior to Surgery
Authors: Orndahl Christine M , Perera Robert A , Riddle Daniel L
Published: September 2020

Objective

Physical therapy visit number and timing following knee arthroplasty (KA) are variable in daily practice. The extent to which the number and timing of physical therapy visits are associated with current and future pain and function—and, alternatively, whether pain and function are associated with the number of future physical therapy visits following KA—are unknown. The purpose of this study was to determine temporal and reciprocal associations between the number of physical therapy visits and future pain and function in people with KA.

Methods

A cross-lagged panel design was applied to a secondary analysis of data from a randomized clinical trial of patients with pain catastrophizing. The 326 participants underwent KA and completed at least 7 of 9 health care diaries over the year following surgery. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function subscales were completed preoperatively and multiple times during follow-up. Separate cross-lagged panel analyses were conducted for WOMAC pain and physical function.

Results

From surgery to 2 months postsurgery, reciprocal associations were generally not found between physical therapy visit number and future pain or function. From 2 to 6 months postsurgery, a greater number of physical therapy weekly visits were associated with higher (worse) 6-month pain and function. Higher (worse) WOMAC pain at 2 and 6 months led to more visits from 2 to 6 and 6 to 12 months, respectively.

Conclusions

Higher pain scores 2 months postsurgery were associated with higher physical therapy use in the 2 to 6 months following surgery. However, patients with increased physical therapy use from 2 to 6 months had significantly higher pain scores 6 months postsurgery. Those patients with persistent pain 6 months postsurgery were higher users of physical therapy 6 to 12 months postsurgery. This reciprocal positive association between pain and physical therapy during this time period suggests minimal benefit of physical therapy despite an increased physical therapy use for patients with higher pain.

Impact

This is the first study to determine the association between the number and timing of physical therapy visits and current and future pain and function. Based on the results, physical therapy might not be a cost-effective strategy to treat patients with persistent pain following KA.
Face-to-Face Communication in Organizations
Authors: Battiston Diego , Blanes i Vidal Jordi , Kirchmaier Tom
Published: September 2020

Communication is integral to organizations and yet field evidence on the relation between communication and worker productivity remains scarce. We argue that a core role of communication is to transmit information that helps co-workers do their job better. We build a simple model in which workers choose the amount of communication by trading off this benefit against the time cost incurred by the sender, and use it to derive a set of empirical predictions. We then exploit a natural experiment in an organization where problems arrive and must be sequentially dealt with by two workers. For exogenous reasons, the first worker can sometimes communicate face-to-face with their colleague. Consistently with the predictions of our model, we find that: (1) the second worker works faster (at the cost of the first worker having less time to deal with incoming problems) when face-to-face communication is possible, (2) this effect is stronger when the second worker is busier and for homogenous and closely located teams, and (3) the (career) incentives of workers determine how much they communicate with their colleagues. We also find that workers partially internalise social outcomes in their communication decisions. Our findings illustrate how workers in teams adjust the amount of mutual communication to its costs and benefits.
A chronology of global air quality
Authors: Fowler David , Brimblecombe Peter , Burrows John , Heal Mathew R. , Grennfelt Peringe , Stevenson David S. , Jowett Alan , Nemitz Eiko , Coyle Mhairi , Liu Xuejun , Chang Yunhua , Fuller Gary W. , Sutton Mark A. , Klimont Zbigniew , Unsworth Mike H. , Vieno Massimo
Published: September 2020

Air pollution has been recognized as a threat to human health since the time of Hippocrates,ca400 BC. Successive written accounts of air pollution occur in different countries through the following two millennia until measurements, from the eighteenth century onwards, show the growing scale of poor air quality in urban centres and close to industry, and the chemical characteristics of the gases and particulate matter. The industrial revolution accelerated both the magnitude of emissions of the primary pollutants and the geographical spread of contributing countries as highly polluted cities became the defining issue, culminating with the great smog of London in 1952. Europe and North America dominated emissions and suffered the majority of adverse effects until the latter decades of the twentieth century, by which time the transboundary issues of acid rain, forest decline and ground-level ozone became the main environmental and political air quality issues. As controls on emissions of sulfur and nitrogen oxides (SO2and NOx) began to take effect in Europe and North America, emissions in East and South Asia grew strongly and dominated global emissions by the early years of the twenty-first century. The effects of air quality on human health had also returned to the top of the priorities by 2000 as new epidemiological evidence emerged. By this time, extensive networks of surface measurements and satellite remote sensing provided global measurements of both primary and secondary pollutants. Global emissions of SO2and NOxpeaked, respectively, inca1990 and 2018 and have since declined to 2020 as a result of widespread emission controls. By contrast, with a lack of actions to abate ammonia, global emissions have continued to grow.

This article is part of a discussion meeting issue ‘Air quality, past present and future’.
Alkaline air: changing perspectives on nitrogen and air pollution in an ammonia-rich world
Authors: Sutton Mark A. , van Dijk Netty , Levy Peter E. , Jones Matthew R. , Leith Ian D. , Sheppard Lucy J. , Leeson Sarah , Sim Tang Y. , Stephens Amy , Braban Christine F. , Dragosits Ulrike , Howard Clare M. , Vieno Massimo , Fowler David , Corbett Paul , Naikoo Mohd Irfan , Munzi Silvana , Ellis Christopher J. , Chatterjee Sudipto , Steadman Claudia E. , Móring Andrea , Wolseley Patricia A.
Published: September 2020

Ammonia and ammonium have received less attention than other forms of air pollution, with limited progress in controlling emissions at UK, European and global scales. By contrast, these compounds have been of significant past interest to science and society, the recollection of which can inform future strategies. Sal ammoniac (
nūshādir
,
nao sha
) is found to have been extremely valuable in long-distance trade (
ca
AD 600–1150) from Egypt and China, where 6–8 kg N could purchase a human life, while air pollution associated with
nūshādir
collection was attributed to this nitrogen form. Ammonia was one of the keys to alchemy—seen as an early experimental mesocosm to understand the world—and later became of interest as ‘alkaline air’ within the eighteenth century development of pneumatic chemistry. The same economic, chemical and environmental properties are found to make ammonia and ammonium of huge relevance today. Successful control of acidifying SO
2
and NO

x

emissions leaves atmospheric NH
3
in excess in many areas, contributing to particulate matter (PM
2.5
) formation, while leading to a new significance of alkaline air, with adverse impacts on natural ecosystems. Investigations of epiphytic lichens and bog ecosystems show how the alkalinity effect of NH
3
may explain its having three to five times the adverse effect of ammonium and nitrate, respectively. It is concluded that future air pollution policy should no longer neglect ammonia. Progress is likely to be mobilized by emphasizing the lost economic value of global N emissions ($200 billion yr
−1
), as part of developing the circular economy for sustainable nitrogen management.

This article is part of a discussion meeting issue ‘Air quality, past present and future’.
Airborne particulate matter
Authors: Harrison Roy M.
Published: September 2020

Airborne particulate matter (PM) is a pollutant of concern not only because of its adverse effects on human health but because of its ability to reduce visibility and soil buildings and materials. It can be regarded as a suite of pollutants since PM covers a very wide range of particle sizes and also has a diverse chemical composition. Historically, much of the PM arose from coal burning and was measured as black smoke. However, in the second half of the twentieth century in developed countries, there was a reduction in black smoke emissions from coal burning and PM steadily became dominated by carbonaceous particles from road traffic exhaust and the secondary pollutants, ammonium salts and secondary organic carbon. This is exemplified by the composition of fine particles (referred to as PM
2.5
) as measured in London, Delhi and Beijing. Steadily, as control strategies have addressed the more tractable sources of emissions, so sources previously regarded as unconventional have emerged and have been seen to make a significant contribution to airborne PM concentrations. Among these are non-exhaust particles from road traffic, cooking aerosol and wood smoke. The particle size distribution of airborne PM is hugely diverse, ranging from newly formed particles of a few nanometres in diameter through to particles of tens of micrometres in diameter. There has been a great deal of interest in ultrafine (nano) particles because of suspicions of enhanced toxicity, and as traffic emissions decrease as a source, so regional nucleation processes have become much bigger relative contributors to particle number, but not mass.

This article is part of a discussion meeting issue ‘Air quality, past present and future’.
Potential and limitation of air pollution mitigation by vegetation and uncertainties of deposition-based evaluations
Authors: Nemitz Eiko , Vieno Massimo , Carnell Edward , Fitch Alice , Steadman Claudia , Cryle Philip , Holland Mike , Morton R. Daniel , Hall Jane , Mills Gina , Hayes Felicity , Dickie Ian , Carruthers David , Fowler David , Reis Stefan , Jones Laurence
Published: September 2020

The potential to capture additional air pollutants by introducing more vegetation or changing existing short vegetation to woodland on first sight provides an attractive route for lowering urban pollution. Here, an atmospheric chemistry and transport model was run with a range of landcover scenarios to quantify pollutant removal by the existing total UK vegetation as well as the UK urban vegetation and to quantify the effect of large-scale urban tree planting on urban air pollution. UK vegetation as a whole reduces area (population)-weighted concentrations significantly, by 10% (9%) for PM
2.5
, 30% (22%) for SO
2
, 24% (19%) for NH
3
and 15% (13%) for O
3
, compared with a desert scenario. By contrast, urban vegetation reduces average urban PM
2.5
by only approximately 1%. Even large-scale conversion of half of existing open urban greenspace to forest would lower urban PM
2.5
by only another 1%, suggesting that the effect on air quality needs to be considered in the context of the wider benefits of urban tree planting, e.g. on physical and mental health. The net benefits of UK vegetation for NO
2
are small, and urban tree planting is even forecast to increase urban NO
2
and NO
x
concentrations, due to the chemical interaction with changes in BVOC emissions and O
3
, but the details depend on tree species selection. By extrapolation, green infrastructure projects focusing on non-greenspace (roadside trees, green walls, roof-top gardens) would have to be implemented at very large scales to match this effect. Downscaling of the results to micro-interventions solely aimed at pollutant removal suggests that their impact is too limited for their cost–benefit analysis to compare favourably with emission abatement measures. Urban vegetation planting is less effective for lowering pollution than measures to reduce emissions at source. The results highlight interactions that cannot be captured if benefits are quantified via deposition models using prescribed concentrations, and emission damage costs.

This article is part of a discussion meeting issue ‘Air quality, past present and future’.
Using epidemiology to estimate the impact and burden of exposure to air pollutants
Authors: Gowers Alison M. , Walton Heather , Exley Karen S. , Hurley J. Fintan
Published: September 2020

This paper focuses on the use of results of epidemiological studies to quantify the effects on health, particularly on mortality, of long-term exposure to air pollutants. It introduces health impact assessment methods, used to predict the benefits that can be expected from implementation of interventions to reduce emissions of pollutants. It also explains the estimation of annual mortality burdens attributable to current levels of pollution. Burden estimates are intended to meet the need to communicate the size of the effect of air pollution on public health to policy makers and others. The implications, for the interpretation of the estimates, of the assumptions and approximations underlying the methods are discussed. The paper starts with quantification based on results obtained from studies of the association of mortality risk with long-term average concentrations of particulate air pollution. It then tackles the additional methodological considerations that need to be addressed when also considering the mortality effects of other pollutants such as nitrogen dioxide (NO
2
). Finally, approaches that could be used to integrate morbidity and mortality endpoints in the same assessment are touched upon.

This article is part of a discussion meeting issue ‘Air quality, past present and future’.
Toxicity of airborne particles—established evidence, knowledge gaps and emerging areas of importance
Authors: Kelly Frank J. , Fussell Julia C.
Published: September 2020

Epidemiological research has taught us a great deal about the health effects of airborne particulate matter (PM), particularly cardiorespiratory effects of combustion-related particles. This has been matched by toxicological research to define underlying mechanistic pathways. To keep abreast of the substantial challenges that air pollution continues to throw at us requires yet more strides to be achieved. For example, being aware of the most toxic components/sources and having a definitive idea of the range of associated disease outcomes. This review discusses approaches designed to close some of these knowledge gaps. These include a focus on particles arising from non-exhaust PM at the roadside and microplastics—both of which are becoming more relevant in the light of a shift in PM composition in response to global pressure to reduce combustion emissions. The application of hypothesis-free approaches in both mechanistic studies and epidemiology in unveiling unexpected relationships and generating novel insights is also discussed. Previous work, strengthening the evidence for both the adverse effects
and
benefits of intervention tell us that the sooner we act to close knowledge gaps, increase awareness and develop creative solutions, the sooner we can reduce the public health burden attributable to these complex and insidious environmental pollutants.

This article is part of a discussion meeting issue ‘Air quality, past present and future’.
Environmental impacts of nitrogen emissions in China and the role of policies in emission reduction
Authors: Liu X. J. , Xu W. , Du E. Z. , Tang A. H. , Zhang Y. , Zhang Y. Y.  , Wen Z. , Hao T. X. , Pan Y. P. , Zhang L. , Gu B. J.  , Zhao Y. , Shen J. L. , Zhou F. , Gao Z. L. , Feng Z. Z.  , Chang Y. H. , Goulding K. , Collett J. L.  , Vitousek P. M. , Zhang F. S. 
Published: September 2020

Atmospheric reactive nitrogen (Nr) has been a cause of serious environmental pollution in China. Historically, China used too little Nrin its agriculture to feed its population. However, with the rapid increase in N fertilizer use for food production and fossil fuel consumption for energy supply over the last four decades, increasing gaseous Nrspecies (e.g. NH3and NOx) have been emitted to the atmosphere and then deposited as wet and dry deposition, with adverse impacts on air, water and soil quality as well as plant biodiversity and human health. This paper reviews the issues associated with this in a holistic way. The emissions, deposition, impacts, actions and regulations for the mitigation of atmospheric Nrare discussed systematically. Both NH3and NOxmake major contributions to environmental pollution but especially to the formation of secondary fine particulate matter (PM2.5), which impacts human health and light scattering (haze). In addition, atmospheric deposition of NH3and NOxcauses adverse impacts on terrestrial and aquatic ecosystems due to acidification and eutrophication. Regulations and practices introduced by China that meet the urgent need to reduce Nremissions are explained and resulting effects on emissions are discussed. Recommendations for improving future N management for achieving ‘win-win’ outcomes for Chinese agricultural production and food supply, and human and environmental health, are described.

This article is part of a discussion meeting issue ‘Air quality, past present and future’.
Understanding sources of fine particulate matter in China
Authors: Zheng Mei , Yan Caiqing , Zhu Tong
Published: September 2020

Fine particulate matter has been a major concern in China as it is closely linked to issues such as haze, health and climate impacts. Since China released its new national air quality standard for fine particulate matter (PM
2.5
) in 2012, great efforts have been put into reducing its concentration and meeting the standard. Significant improvement has been seen in recent years, especially in Beijing, the capital city of China. This paper reviews how China understands its sources of fine particulate matter, the major contributor to haze, and the most recent findings by researchers. It covers the characteristics of PM
2.5
in China, the major methods to understand its sources such as emission inventory and measurement networks, the major research programmes in air quality research, and the major measures that lead to successful control of fine particulate matter pollution. A great example of linking scientific findings to policy is the control of coal combustion from the residential sector in northern China. This review not only provides an overview of the fine particulate matter pollution problem in China, but also its experience of air quality management, which may benefit other countries facing similar issues.

This article is part of a discussion meeting issue ‘Air quality, past present and future’.
Effects of ozone on agriculture, forests and grasslands
Authors: Emberson Lisa
Published: September 2020

The damage and injury that ground level ozone (O
3
) causes vegetation has become increasingly evident over the past half century with a large body of observational and experimental evidence demonstrating a variety of effects at ambient concentrations on crop, forest and grassland species and ecosystems. This paper explores the use of experimental data to develop exposure-response relationships for use in risk assessment studies. These studies have typically identified the USA mid-West, much of Europe, the Indo Gangetic Plain in South Asia and the Eastern coastal region of China as global regions where O
3
is likely to threaten food supply and other ecosystems. Global risk assessment modelling estimates yield losses of staple crops between 3 to 16% causing economic losses of between US$14 to 26 billion in the year 2000. Changes in anthropogenic emissions of O
3
precursors in recent decades have modified O
3
concentration profiles (peaks versus background O
3
) and global distributions with the Northern Hemisphere seeing increases in O
3
levels of between 1 and 5 ppb/decade since the 1950s and the emergence of Asia as the region with the highest O
3
concentrations. In the future, O
3
mitigation could focus on methane (CH
4
) and nitrogen oxide (NOx) emissions; these will differentially influence global and local/regional O
3
concentrations and influence daily and seasonal profiles. The consequent effects on vegetation will in part depend on how these changes in O
3
profile alter the exceedance of detoxification thresholds for plant damage. Adaptation options may play an important role in enhancing food supply while mitigation strategies are being implemented. An improved understanding of the mechanisms by which O
3
affects plants, and how this might influence detoxification thresholds and interactions with other environmental variables such as water stress and nutrients, would help develop O
3
deposition and impact models to support the development of crop, land-surface exchange and ultimately earth system models for holistic assessments of global change.

This article is part of a discussion meeting issue ‘Air quality, past present and future’.
On the changes in surface ozone over the twenty-first century: sensitivity to changes in surface temperature and chemical mechanisms
Authors: Archibald Alex T. , Turnock Steven T. , Griffiths Paul T. , Cox Tony , Derwent Richard G. , Knote Christoph , Shin Matthew
Published: September 2020

In this study, we show using a state-of-the-art Earth system model, UKESM1, that emissions and climate scenario depending, there could be large changes in surface ozone by the end of the twenty-first century, with unprecedentedly large increases over South and East Asia. We also show that statistical modelling of the trends in future ozone works well in reproducing the model output between 1900 and 2050. However, beyond 2050, and especially under large climate change scenarios, the statistical model results are in poorer agreement with the fully interactive Earth system model output. This suggests that additional processes occurring in the Earth system model such as changes in the production of ozone at higher temperatures or changes in the influx of ozone from the stratosphere, which are not captured by the statistical model, have a first order impact on the evolution of surface ozone over the twenty-first century. We show in a series of idealized box model simulations, with two different chemical schemes, that changes in temperature lead to diverging responses between the schemes. This points at the chemical mechanisms as being a source of uncertainty in the response of ozone to changes in temperature, and so climate, in the future. This underscores the need for more work to be performed to better understand the response of ozone to changes in temperature and constrain how well this relationship is simulated in models.

This article is part of a discussion meeting issue ‘Air quality, past present and future’.
Lower air pollution during COVID-19 lock-down: improving models and methods estimating ozone impacts on crops
Authors: Dentener Frank , Emberson Lisa , Galmarini Stefano , Cappelli Giovanni , Irimescu Anisoara , Mihailescu Denis , Van Dingenen Rita , van den Berg Maurits
Published: September 2020

We suggest that the unprecedented and unintended decrease of emissions of air pollutants during the COVID-19 lock-down in 2020 could lead to declining seasonal ozone concentrations and positive impacts on crop yields. An initial assessment of the potential effects of COVID-19 emission reductions was made using a set of six scenarios that variously assumed annual European and global emission reductions of 30% and 50% for the energy, industry, road transport and international shipping sectors, and 80% for the aviation sector. The greatest ozone reductions during the growing season reached up to 12  ppb over crop growing regions in Asia and up to 6 ppb in North America and Europe for the 50% global reduction scenario. In Europe, ozone responses are more sensitive to emission declines in other continents, international shipping and aviation than to emissions changes within Europe. We demonstrate that for wheat the overall magnitude of ozone precursor emission changes could lead to yield improvements between 2% and 8%. The expected magnitude of ozone precursor emission reductions during the Northern Hemisphere growing season in 2020 presents an opportunity to test and improve crop models and experimentally based exposure response relationships of ozone impacts on crops, under real-world conditions.

This article is part of a discussion meeting issue ‘Air quality, past present and future’.
Evidence for non-Mendelian inheritance in spastic paraplegia 7
Authors: Estiar Mehrdad A , Yu Eric , Salem Ikhlass Haj , Ross Jay P. , Mufti Kheireddin , Akçimen Fulya , Leveille Etienne , Spiegelman Dan , Ruskey Jennifer A. , Asayesh Farnaz , Dagher Alain , Yoon Grace , Tarnopolsky Mark , Boycott Kym M. , Dupre Nicolas , Dion Patrick A. , Suchowersky Oksana , Trempe Jean-Francois , Rouleau Guy A. , Gan-Or Ziv
Published: September 2020

Hereditary spastic paraplegia is a group of rare motor neuron diseases considered to be inherited in a classical monogenic Mendelian manner. Although the typical inheritance of spastic paraplegia type 7 is autosomal recessive, several reports have suggested that SPG7 variants may also cause autosomal dominant HSP. We aimed to conduct an exome-wide genetic analysis on a large Canadian cohort of hereditary spastic paraplegia patients and controls to examine the association of SPG7 and hereditary spastic paraplegia. In total, 585 hereditary spastic paraplegia patients from 372 families and 1,175 controls, including 580 unrelated individuals, were analyzed for the presence of SPG7 variants. Whole exome sequencing was performed on 400 hereditary spastic paraplegia patients (291 index cases) and all 1,175 controls. After excluding 38 biallelic hereditary spastic paraplegia type 7 patients, the frequency of heterozygous pathogenic/likely pathogenic SPG7 variant carriers (4.8%) among hereditary spastic paraplegia unrelated index cases who underwent WES, was significantly higher than among unrelated controls (1.7%; OR=2.88, 95%CI=1.24-6.66, p=0.009). The heterozygous SPG7 p.(Ala510Val) variant was found in 3.7% of index cases vs. 0.85% in unrelated controls (OR=4.42, 95%CI=1.49-13.07, p=0.005). We identified four heterozygous SPG7 variant carriers with an additional pathogenic variant in genes known to cause hereditary spastic paraplegia, compared to zero in controls (OR=19.58, 95%CI=1.05-365.13, p=0.0031; Fisher’s Exact test with Haldane-Anscombe correction), indicating potential digenic inheritance. We further identified four families with heterozygous variants in SPG7 and SPG7-interacting genes (CACNA1A, AFG3L2 and MORC2). Out of these, there is especially compelling evidence for epistasis between SPG7 and AFG3L2. The p.(Ile705Thr) variant in AFG3L2 is located at the interface between hexamer subunits, in a hotspot of mutations associated with spinocerebellar ataxia type 28 that affect its proteolytic function. Our results provide evidence for complex inheritance in SPG7-associated hereditary spastic paraplegia, which may include recessive and possibly dominant and digenic/epistasis forms of inheritance.
Influence of COVID-19 confinement measures on appendectomies in Germany – administrative claims data analysis of 9,797 patients
Authors: Maneck Matthias , Günster Christian , Meyer Hans-Joachim , Heidecke Claus-Dieter , Rolle Udo
Published: September 2020

Purpose

COVID 19 pandemic had multiple influences on the social, industrial and medical situation in all affected countries. Measures of obligatory medical confinement were suspensions of scheduled non-emergent surgical procedures and outpatients’ clinics as well as overall access restrictions to hospitals and medical practices.

The aim of this retrospective study was to assess if the obligatory confinement (lockdown) had an effect on the number of appendectomies (during and after the period of lockdown).

Methods

This retrospective study was based on anonymized nationwide administrative claims data of the German Local General Sickness Fund (AOK). Patients admitted for disease of the appendix (ICD-10: K35-K38) or abdominal and pelvic pain (ICD-10: R10) who undergone an appendectomy (OPS: 5-470) were included. The study period included six weeks of German lockdown (16.03.-26.04.2020) as well as six weeks before (03.02.-15.03.2020) and after (27.04.-07.06.2020). These periods were compared to the respective in 2019.

Results

Overall number of appendectomies was significantly reduced during the lockdown time in 2020 compared to 2019. This decrease affects only appendectomies due to acute simple and non-acute appendicitis. Numbers for appendectomies in acute complex appendicitis remained unchanged. Female patients and in the age group 1-18 years showed the strongest decrease in number of cases.

Conclusion

The lockdown in Germany resulted in a decreased number of appendectomies. This affected mainly appendectomies in simple acute and non-acute appendicitis, but not complicated acute appendicitis. The study gives no evidence, that the confinement measures resulted in a deterioration of medical care for appendicitis.

Authors contributions

MM performed study conception, acquisition of data, analysis and interpretation of data, drafting the manuscript. CG performed study conception, analysis and interpretation of data, drafting the manuscript, critical revision of manuscript.

HJM performed study conception and critical revision of manuscript.

CDH performed study conception and critical revision of manuscript.

UR performed study conception, drafting the manuscript and critical revision of manuscript
Each patient is a research biorepository: Informatics-enabled research on surplus clinical specimens via the Living BioBank
Authors: Alekseyenko Alexander V. , Hamidi Bashir , Faith Trevor D. , Crandall Keith A. , Powers Jennifer G. , Metts Christopher L. , Madory James E. , Carroll Steven L. , Obeid Jihad S. , Lenert Leslie A.
Published: September 2020

The ability to analyze human specimens is the pillar of modern-day translational research. To enhance the research availability of relevant clinical specimens, we developed the Living BioBank (LBB) solution, which allows for just-in-time capture and delivery of phenotyped surplus laboratory medicine specimens. The LBB is a system-of-systems integrating research feasibility databases in i2b2, a real time clinical data warehouse, and an informatics system for institutional research services management (SPARC). LBB delivers de-identified clinical data and laboratory specimens. We further present an extension to our solution, the Living µBiome Bank, that allows the user to request and receive phenotyped specimen microbiome data. We discuss the details of the implementation of the LBB system and the necessary regulatory oversight for this solution. The conducted institutional focus group of translational investigators indicates an overall positive sentiment towards potential scientific results generated with the use of LBB. Reference implementation of LBB is available at https://LivingBioBank.musc.edu.
Predict multicategory causes of death in lung cancer patients using clinicopathologic factors
Authors: Deng Fei , Zhou Haijun , Lin Yong , Heim John , Shen Lanlan , Li Yuan , Zhang Lanjing
Published: September 2020

Background

Random forest model is a recently developed machine-learning algorithm, and superior to other machine learning and regression models for its classification function and better accuracy. But it is rarely used for predicting causes of death in lung cancer patients. On the other hand, specific causes of death in lung cancer patients are poorly classified or predicted, largely due to its categorical nature (versus binary death/survival).

Methods

We therefore tuned and employed a random forest algorithm (Stata, version 15) to classify and predict specific causes of death in lung cancer patients, using the surveillance, epidemiology and end results-18 and several clinicopathological factors. The lung cancer diagnosed during 2004 were included for the completeness in their follow-up and death causes. The patients were randomly divided into training and validation sets (1:1 match). We also compared the accuracies of the final random forest and multinomial regression models.

Results

We identified and randomly selected 40,000 lung cancers for the analyses, including 20,000 cases for either set. The causes of death were, in descending ranking order, were lung cancer (72.45 %), other causes or alive (14.38%), non-lung cancer (6.87%), cardiovascular disease (5.35%), and infection (0.95%). We found more 250 iterations and the 10 variables produced the best prediction, whose best accuracy was 69.8% (error-rate 30.2%). The final random forest model with 300 iterations and 10 variables reached an accuracy higher than that of multinomial regression model (69.8% vs 64.6%). The top-10 most important factors in the random-forest model were sex, chemotherapy status, age (65+ vs <65 years), radiotherapy status, nodal status, T category, histology type and laterality, which were also independently associated with 5-category causes of death.

Conclusion

We optimized a random forest model of machine learning to predict the specific cause of death in lung cancer patients using a set of clinicopathologic factors. The model also appears more accurate than multinomial regression model.
The effect of mobile applications for menstrual cycle or fertility trackers on women’s health: protocol for a systematic review
Authors: Nomura-Sakata Andrea I. , Mogrovejo-Navas Cinthya I. , Navarro-Grau Alejandra , Zafra-Tanaka Jessica Hanae
Published: September 2020

Background

Nowadays the use of smartphones and the development of health-related mobile applications has increased worldwide. Menstrual cycle tracking applications (MCTAs) have become especially popular among women because of their practicality in recording menstrual cycles, characteristics of bleeding and prediction of cycle stages. There are various studies regarding the use of MCTAs for different aspects of women’s health such as estimating a fertility window for both conception and contraception, help register last menstrual period for calculation of gestational age, record pre-menstrual symptoms, among others. However, effects of MCTAs have not been analyzed in a systematic review.

Objective

The aim of this study is to evaluate the effect of mobile applications for menstrual cycle or fertility trackers on women’s health.

Methods

A systematic review will be conducted, starting with a search in PubMed, CENTRAL and Scopus using search terms related to mobile applications and menstrual or fertility tracking. Only randomized controlled trials will be screened with a sample of child-bearing aged women that use menstrual or fertility tracking mobile applications. Selected studies will be fully analyzed and the results will be recorded on a spread sheet. Study selection and data extraction will be conducted by two reviewers independently and the Cochrane Risk of Bias Tool for RCT will be used for assessment of risk of bias. Discrepancies will be reviewed with a third reviewer.

Conclusion

Currently, there is a lack of information on the effects of using MCTAs on women’s health. This systematic review aims to provide an analysis on the outcomes of the usage of these applications and evaluate any potential effects.

Conflicts of interest

All authors declare to have no conflicts of interest.
Quantitative, Epitope-specific, Serological Screening of COVID-19 Patients Using a Novel Multiplexed Array-based Immunoassay Platform
Authors: Blackburn JM , Anuar ND , Tan TM , Nel AJM , Smith M , Ellan K , Bahrin NIS , Rosli NSM , Badri NH , Rahman TNA , Anwar A , Zain RM
Published: September 2020

Following the COVID-19 pandemic outbreak in late 2019, a large number of antibody tests were developed for use in seroprevalence studies aimed at determining the extent of current or previous SARS-CoV-2 virus infections in a given population. The vast majority of these tests are qualitative and use a single target for antibody detection, incorporating either full-length or truncated versions of the nucleocapsid (N) or spike (S) proteins from SARS-CoV-2. Importantly, mono-epitope tests – whether qualitative or quantitative - are unable to localise antibody binding or characterise the distribution and titres of epitope recognition by anti-SARS-CoV-2 antibodies within an individual or across a population. However, it seems plausible that if such information were available, it may correlate with the presence of potent, high-titre, neutralising antibodies that afford protection again imminent re-infection, as well as with the likelihood of developing a memory B-cell response that would provide more durable protection. We have developed a novel, quantitative, multi-antigen, multiplexed, array-based immunoassay platform, ‘ImmuSAFE COVID+’ (ImmuSAFE) comprising 6 functionally validated domains or regions of the N protein of SARS-CoV-2 expressed using Sengenics’ KREX technology. This array platform enables determination of both the position and breadth of anti-SARS-CoV-2 antibody responses following natural infection or vaccination. To validate our platform, 100 serum samples (confirmed sero-positive COVID-19 cases, n=50; pre-pandemic HIV positive controls, n=50) were tested for IgG seropositivity to the N antigen, yielding 100% specificity and 100% sensitivity. All 50 cases showed positive antibody reactivity towards at least one N protein epitope, whilst all 50 controls showed antibody reactivity below threshold values. Broad variation was also observed in the magnitude and breadth of antibodies present, represented as an Epitope Coverage score (EPC). A positive correlation was observed between increasing age and EPC values, with individuals under 40 years old having a mean EPC score of 3.1, whilst individuals above the age of 60 had a mean EPC of 5.1. This finding may have broad implications for the natural history of COVID-19 disease in different individuals.
The association between influenza vaccination and the risk of SARS-CoV-2 infection, severe illness, and death: a systematic review of the literature
Authors: Del Riccio Marco , Lorini Chiara , Bonaccorsi Guglielmo , Paget John , Caini Saverio
Published: September 2020

We reviewed the association between seasonal influenza vaccination and the risk of SARS-CoV-2 infection or complicated illness or poor outcome (e.g. severe disease, need for hospitalization or ventilatory support, or death) among COVID-19 patients. None of the studies that were reviewed (n=12) found a significant increase in the risk of infection or in the illness severity or lethality, while some reported significantly inverse associations. Our findings support measures aimed at raising influenza vaccination coverage in the coming months.
An electronic application to improve management of infections in low-income neonatal units: pilot implementation of the NeoTree Beta App in a public sector hospital in Zimbabwe
Authors: Gannon H , Chimhuya S , Chimhini G , Neal S. R. , Shaw L P , Crehan C , Bailey T Hull , Ferrand R. A. , Klein N , Sharland M , Robertson V , Borja M Cortina , Heys M. , Fitzgerald F
Published: September 2020

There are 2.9 million annual neonatal deaths worldwide. Simple, evidence-based interventions such as temperature control could prevent approximately two-thirds of these deaths. However, key problems in implementing these interventions are a lack of newborn-trained healthcare workers and a lack of data collection systems. NeoTree is a digital platform aiming to improve newborn care in low-resource settings through real-time data capture and feedback alongside education and data linkage. This project demonstrates proof of concept of the NeoTree as a real-time data capture tool replacing hand-written clinical paper notes over a 9-month period in a tertiary neonatal unit at Harare Central hospital, Zimbabwe. We aimed to deliver robust data for monthly mortality and morbidity meetings, and to improve turn-around time for blood culture results among other quality improvement indicators.

There were 3222 admissions and discharges entered using the NeoTree software with 41 junior doctors and 9 laboratory staff trained over the 9-month period. The NeoTree app was fully integrated into the department for all admission and discharge documentation and the monthly presentations became routine, informing local practice. An essential factor for this success was local buy-in and ownership at each stage of the project development, as was monthly data analysis and presentations allowing us to rapidly troubleshoot emerging issues. However, the laboratory arm of the project was negatively affected by nationwide economic upheaval. Our successes and challenges piloting this digital tool have provided key insights for effective future roll-out in Zimbabwe and other low-income healthcare settings.
A Systematic Review of Randomised Controlled Trials on the Effectiveness of Ecotherapy Interventions for Treating Mental Disorders
Authors: Williams T. , Barnwell G.C. , Stein D.J.
Published: September 2020

Background

Systematic reviews on ecotherapy interventions (i.e. environmental therapies and animal-assisted therapies) in the general population have demonstrated promising findings. However, there is a need for systematic assessment of the evidence for the use of these interventions in people living with mental disorders. Hence, we conducted a systematic review of randomised control trials (RCTs) on exposure to ecotherapy interventions (i.e. environmental therapy, animal-assisted therapy, wilderness therapy) for individuals with mental disorders.

Methods

The search was completed in September 2019 and comprised: Science Direct, PubMed Central, EBSCOHOST (via Academic Search Premier), the Cochrane Library, and Google Scholar. The primary outcomes that were assessed include: treatment efficacy (on the CGI-I or similar), symptom severity, and/or dropout rates. Secondary outcome measures assessed included self-efficacy, perceived control, hope, quality of life, life skills, and coping.

Results

A total of 2415 reports were identified, of which 94 were assessed for eligibility. Eight environmental therapy trials (i.e. gardening, forest therapy, horticultural therapy, nature adventure rehabilitation, and adventure-based therapy) and ten animal-assisted therapy trials (i.e. dogs, horses or dolphins) were included in the review. Risk of bias assessment was conducted, and qualitative analysis performed to describe the efficacy of the RCTs. The findings suggest that environmental therapies or animal-assisted therapies are efficacious in reducing symptoms of anxiety, depressive, substance-related and addictive, schizophrenia-spectrum and trauma- and stress-related disorders.

Conclusion

There is suggestive, but not conclusive, evidence for the efficacy of some ecotherapy interventions in mental disorders. In particular, there are: four environmental therapy trials and five animal-assisted therapy trails for depression and/or anxiety; one environmental therapy trial for post-traumatic stress disorder; three environmental therapy and animal assisted therapy trials for general psychiatric disorders; one environmental therapy trial and two animal assisted therapy trials for substance use disorders; and, one environmental therapy and two animal-assisted trials for people living with schizophrenia spectrum disorder. The use of standard reporting guidelines may improve evidence quality of future ecotherapy RCTs, and provide a foundation meta-analysis of the evidence.
A combined oro-nasopharyngeal swab is more sensitive than mouthwash in detecting SARS-CoV-2 by a high-throughput PCR assay
Authors: Michel Wiebke , Färber Jacqueline , Dilas Milica , Tammer Ina , Baar Jannik , Kaasch Achim J.
Published: September 2020

Objectives

The optimal diagnostic specimen to detect SARS-CoV-2 by PCR in the upper respiratory tract is unclear. Mouthwash fluid has been reported as an alternative to nasopharyngeal and oropharyngeal swabs. We compared mouthwash fluid with a combined oro-nasopharyngeal swab regarding test performance.

Methods

We tested asymptomatic persons with a previous diagnosis of COVID-19 and their household contacts. First, a mouthwash (gargling for at least 5 sec) with sterile water was performed. Then, with a single flocked swab the back of the throat and subsequently the nasopharynx were sampled. Samples were inactivated and analysed on a Roche cobas 6800® system with the Roche SARS-CoV-2 test.

Results

Of 76 persons, 39 (51%) tested positive for SARS-CoV-2 by oro-nasopharyngeal swab. Mouthwash detected 13 (17%) of these infections but did not detect any additional infection. Samples that were positive in both tests, had lower cycle threshold (Ct)-values for oro-nasopharyngeal samples, indicating a higher virus concentration, compared to samples only positive in oro-nasopharyngeal swabs.

Conclusions

Mouthwash is not as sensitive as combined oro-nasopharyngeal swab in detecting upper respiratory tract infection.
Modeling COVID-19 as a National Dynamics with a SARS-CoV-2 Prevalent Variant: Brazil - A Study Case
Authors: Celaschi S.
Published: September 2020

COVID-19 global dynamics is modeled by an adaptation of the deterministic SEIR Model, which takes into account two dominant lineages of the SARS-CoV-2, and a time-varying reproduction number to estimate the disease transmission behavior. Such a methodology can be applied worldwide to predict forecasts of the outbreak in any infected country. The pandemic in Brazil was selected as a first study case. Brazilian official published data from February 25th to August 30th, 2020 was used to adjust a few epidemiologic parameters. The estimated time-dependence mean value to the infected individuals (confirmed cases) presents - in logarithmic scale - standard deviation SD = 0.08 for over six orders of magnitude. Data points for additional three weeks were added after the model was complete, granting confidence on the outcomes. By the end of 2020, the predicted numbers of confirmed cases in Brazil, within 95% credible intervals, may reach 6 Million (5 -7), and fatalities would accounts for 180 (130 – 220) thousands. The total number of infected individuals is estimated to reach 13 ± 1 Million, 6.2% of the Brazilian population. Regarding the original SARS-CoV-2 form and its variant, the only model assumption is their distinct incubation rates. The variant form reaches a maximum of 96% of exposed individuals as previously reported for South America.