bluuebunny/crossref_metadata_2025 huggingface dataset:
An Ecological Insight Into the Design and Integration of Attacking Principles of Play in Professional Rugby Union: A Case Example
Authors: McKay Jim , Davids Keith , Robertson Sam , Woods Carl T.
Published: February 2021

This is an exciting era for applied research in high-performance sporting environments. Specifically, there are growing calls for researchers to work with coaches to produce “real-world” case examples that offer first-hand experiences into the application of theory. While ecological dynamics has emerged as a guiding theoretical framework for learning and performance in sport, there is a caveat to its use in the field. Namely, there is a general paucity of applied research that details how expert coaches have brought life to its theoretical contentions in practice. In light of this, the current paper offers a unique insight into how a professional Rugby union organization set out to ground their preparation for competitive performance within an ecological dynamics framework. More directly, this paper details how the Queensland Reds designed and integrated a set of attacking game principles that afforded players with opportunities in practice to search, discover, and exploit their actions. While this paper offers insight specific to Rugby union, its learnings are transferrable to coaches in other sports looking to situate their practice design within an ecological dynamics framework.
Application of Convolutional Neural Network Algorithms for Advancing Sedentary and Activity Bout Classification
Authors: Nakandala Supun , Jankowska Marta M. , Tuz-Zahra Fatima , Bellettiere John , Carlson Jordan A. , LaCroix Andrea Z. , Hartman Sheri J. , Rosenberg Dori E. , Zou Jingjing , Kumar Arun , Natarajan Loki
Published: February 2021

Background: Machine learning has been used for classification of physical behavior bouts from hip-worn accelerometers; however, this research has been limited due to the challenges of directly observing and coding human behavior “in the wild.” Deep learning algorithms, such as convolutional neural networks (CNNs), may offer better representation of data than other machine learning algorithms without the need for engineered features and may be better suited to dealing with free-living data. The purpose of this study was to develop a modeling pipeline for evaluation of a CNN model on a free-living data set and compare CNN inputs and results with the commonly used machine learning random forest and logistic regression algorithms. Method: Twenty-eight free-living women wore an ActiGraph GT3X+ accelerometer on their right hip for 7 days. A concurrently worn thigh-mounted activPAL device captured ground truth activity labels. The authors evaluated logistic regression, random forest, and CNN models for classifying sitting, standing, and stepping bouts. The authors also assessed the benefit of performing feature engineering for this task. Results: The CNN classifier performed best (average balanced accuracy for bout classification of sitting, standing, and stepping was 84%) compared with the other methods (56% for logistic regression and 76% for random forest), even without performing any feature engineering. Conclusion: Using the recent advancements in deep neural networks, the authors showed that a CNN model can outperform other methods even without feature engineering. This has important implications for both the model’s ability to deal with the complexity of free-living data and its potential transferability to new populations.
T cell circuits that sense antigen density with an ultrasensitive threshold
Authors: Hernandez-Lopez Rogelio A. , Yu Wei , Cabral Katelyn A. , Creasey Olivia A. , Lopez Pazmino Maria del Pilar , Tonai Yurie , De Guzman Arsenia , Mäkelä Anna , Saksela Kalle , Gartner Zev J. , Lim Wendell A.
Published: February 2021

Designing smarter anticancer T cells

Biological signaling systems can exhibit a large, nonlinear—or “ultrasensitive”—response, which would be useful to engineer into therapeutic T cells to allow for better discrimination between cancer cells and normal tissues. Hernandez-Lopez
et al.
modified human T cells using a two-step mechanism that allowed them to kill cells expressing large amounts of cancer marker protein but not cells expressing a small amount of the same protein. A first synthetic receptor recognized the antigen with low affinity. That receptor signaled to increase expression of a chimeric antigen receptor (CAR) with high affinity for the same antigen. The circuit proved effective in cell culture and mouse cancer models, offering hope of extending the CAR T cell strategy against solid tumors.

Science
, this issue p.
1166
Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair
Authors: He Lingjuan , Pu Wenjuan , Liu Xiuxiu , Zhang Zhenqian , Han Maoying , Li Yi , Huang Xiuzhen , Han Ximeng , Li Yan , Liu Kuo , Shi Mengyang , Lai Liang , Sun Ruilin , Wang Qing-Dong , Ji Yong , Tchorz Jan S. , Zhou Bin
Published: February 2021

Zoning in on liver growth

For organ homeostasis or regrowth after injury or disease, one or more stem cell populations is needed to rebuild lost tissue. There is considerable debate about the source of new cells in the liver. Two groups now identify the source of new hepatocytes (see the Perspective by Andersson). Although the liver may seem to lack major variation across its structure, its lobule is organized into concentric zones where hepatocytes express different metabolic enzymes. Wei
et al.
sought to systematically define the source of new liver cells by comparing 14 fate-mapping mice that label different liver cell types. They found that different regions of the liver lobule exhibit differences in hepatocyte turnover, with zone 2 representing a primary source of new hepatocytes during homeostasis and regeneration. Similarly, He
et al.
designed a genetic approach to record cell proliferation in vivo with high spatial and temporal resolution to enable continuous recording of proliferative events of any specific cell type at the whole-cell population level. Using this method, they identified zone 2 as having the highest proliferative activity and contributing the most to liver regrowth. These findings have implications for the cellular basis of chronic disease pathogenesis, cancer development, and regenerative medicine strategies.

Science
, this issue p.
eabb1625
, p.
eabc4346
; see also p.
887
Molecular mechanism of cytokinin-activated cell division in
Arabidopsis
Authors: Yang Weibing , Cortijo Sandra , Korsbo Niklas , Roszak Pawel , Schiessl Katharina , Gurzadyan Aram , Wightman Raymond , Jönsson Henrik , Meyerowitz Elliot
Published: February 2021

Cell cycle regulation

The hormone cytokinin regulates various aspects of plant development and physiology, largely by managing cell proliferation. Yang
et al.
show that cytokinin promotes nuclear localization of the transcription factor MYB3R4, which activates the expression of two importins and genes that tip the cell into the next phase of the cell cycle. The importins facilitate further MYB3R4 accumulation within the nucleus, accelerating the progression into mitosis. MYB3R4 and the importins dissipate when the nuclear membrane dissolves at prometaphase, so there is only one round of mitotic activation per cell cycle.

Science
, this issue p.
1350
Quantum interference between spin-orbit split partial waves in the F + HD → HF + D reaction
Authors: Chen Wentao , Wang Ransheng , Yuan Daofu , Zhao Hailin , Luo Chang , Tan Yuxin , Li Shihao , Zhang Dong H. , Wang Xingan , Sun Zhigang , Yang Xueming
Published: February 2021

Intriguing dynamics pattern in F + HD

Despite decades of studies, the role of relativistic spin-orbit interactions in the dynamics of chemical reactions remains an intriguing topic. Using a high-resolution velocity map imaging crossed beams technique, Chen
et al.
observed an interesting pattern in the differential cross sections in the F + HD → HF + D reaction near the partial wave resonances (see the Perspective by Rakitzis). Further theoretical analysis showed that this pattern originates from quantum interference between spin-orbit split partial wave resonances with different total parities. The effect of the fine structure of the partial waves observed for this long known yet not completely explored three-atom system represents one more remarkable demonstration of the truly quantum nature of chemical reaction dynamics.

Science
, this issue p.
936
; see also p.
886
Haplotype-resolved diverse human genomes and integrated analysis of structural variation
Authors: Ebert Peter , Audano Peter A. , Zhu Qihui , Rodriguez-Martin Bernardo , Porubsky David , Bonder Marc Jan , Sulovari Arvis , Ebler Jana , Zhou Weichen , Serra Mari Rebecca , Yilmaz Feyza , Zhao Xuefang , Hsieh PingHsun , Lee Joyce , Kumar Sushant , Lin Jiadong , Rausch Tobias , Chen Yu , Ren Jingwen , Santamarina Martin , Höps Wolfram , Ashraf Hufsah , Chuang Nelson T. , Yang Xiaofei , Munson Katherine M. , Lewis Alexandra P. , Fairley Susan , Tallon Luke J. , Clarke Wayne E. , Basile Anna O. , Byrska-Bishop Marta , Corvelo André , Evani Uday S. , Lu Tsung-Yu , Chaisson Mark J. P. , Chen Junjie , Li Chong , Brand Harrison , Wenger Aaron M. , Ghareghani Maryam , Harvey William T. , Raeder Benjamin , Hasenfeld Patrick , Regier Allison A. , Abel Haley J. , Hall Ira M. , Flicek Paul , Stegle Oliver , Gerstein Mark B. , Tubio Jose M. C. , Mu Zepeng , Li Yang I. , Shi Xinghua , Hastie Alex R. , Ye Kai , Chong Zechen , Sanders Ashley D. , Zody Michael C. , Talkowski Michael E. , Mills Ryan E. , Devine Scott E. , Lee Charles , Korbel Jan O. , Marschall Tobias , Eichler Evan E.
Published: February 2021

Resolving genomic structural variation

Many human genomes have been reported using short-read technology, but it is difficult to resolve structural variants (SVs) using these data. These genomes thus lack comprehensive comparisons among individuals and populations. Ebertet al.used long-read structural variation calling across 64 human genomes representing diverse populations and developed new methods for variant discovery. This approach allowed the authors to increase the number of confirmed SVs and to describe the patterns of variation across populations. From this dataset, they identified quantitative trait loci affected by these SVs and determined how they may affect gene expression and potentially explain genome-wide association study hits. This information provides insights into patterns of normal human genetic variation and generates reference genomes that better represent the diversity of our species.

Science, this issue p.eabf7117
Was “science” on the ballot?
Authors: Hilgartner Stephen , Hurlbut J. Benjamin , Jasanoff Sheila
Published: February 2021

Labeling dissent as “anti-science” is bad social science and bad politics
Market design to accelerate COVID-19 vaccine supply
Authors: Castillo Juan Camilo , Ahuja Amrita , Athey Susan , Baker Arthur , Budish Eric , Chipty Tasneem , Glennerster Rachel , Kominers Scott Duke , Kremer Michael , Larson Greg , Lee Jean , Prendergast Canice , Snyder Christopher M. , Tabarrok Alex , Tan Brandon Joel , Więcek Witold
Published: February 2021

Build more capacity, and stretch what we already have
Controlling quantum many-body dynamics in driven Rydberg atom arrays
Authors: Bluvstein D. , Omran A. , Levine H. , Keesling A. , Semeghini G. , Ebadi S. , Wang T. T. , Michailidis A. A. , Maskara N. , Ho W. W. , Choi S. , Serbyn M. , Greiner M. , Vuletić V. , Lukin M. D.
Published: February 2021

Dynamic stabilization of an array

Large-scale systems comprising one-dimensional chains and two-dimensional arrays of excited atoms held in a programmable optical lattice are a powerful platform with which to simulate emergent phenomena. Bluvstein
et al.
built an array of up to 200 Rydberg atoms and subjected the system to periodic excitation. Under such driven excitation, they found that the array of atoms stabilized, freezing periodically into what looked like time crystals. Understanding and controlling the dynamic interactions in quantum many-body systems lies at the heart of contemporary condensed matter physics and the exotic phenomena that can occur.

Science
, this issue p.
1355
Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes
Authors: White Kirsten L. , Osman Nathan , Cuadra-Foy Ernesto , Brenner Bluma G. , Shivakumar Devleena , Campigotto Federico , Tsiang Manuel , Morganelli Philip A. , Novikov Nikolai , Lazerwith Scott E. , Jin Haolun , Niedziela-Majka Anita
Published: February 2021

The HIV integrase (IN) strand transfer inhibitor (INSTI) bictegravir (BIC) has a long dissociation half-life (
t
1/2
) from wild-type IN-DNA complexes: BIC 163 h > dolutegravir (DTG) 96 h > raltegravir (RAL) 10 h > elvitegravir (EVG) 3.3 h. In cells, BIC had more durable antiviral activity against wild-type HIV after drug washout than RAL or EVG.
Potential Differences in Cleavage of the S Protein and Type 1 Interferon Together Control Human Coronavirus Infection, Propagation, and Neuropathology within the Central Nervous System
Authors: Le Coupanec Alain , Desforges Marc , Kaufer Benedikt , Dubeau Philippe , Côté Marceline , Talbot Pierre J.
Published: February 2021

Human coronaviruses (HCoV) are recognized respiratory pathogens. The emergence of the novel pathogenic member of this family in December 2019 (SARS-CoV-2, which causes COVID-19) poses a global health emergency.
Decoding the Molecular Properties of Mycobacteriophage D29 Holin Provides Insights into Holin Engineering
Authors: Bavda Varun Rakeshbhai , Yadav Aditi , Jain Vikas
Published: February 2021

Holins are bacteriophage-encoded small membrane perforators that play an important role in determining the timing of host cell lysis toward the end of the phage infection cycle. The ability of holin to precisely time the hole formation in the cell membrane, ensuring cell lysis, is both interesting and intriguing. Here, we examined the molecular properties of the mycobacteriophage D29 holin C-terminal region, which harbors several polar charged residues and a coiled-coil domain.
Late Mesoproterozoic low-P/T–type metamorphism in the North Wulan terrane: Implications for the assembly of Rodinia
Authors: Wang Lu , Johnston Stephen T. , Chen Nengsong , Wang Heng , Xia Bin , He Chuan , Ma Jianjun
Published: February 2021

Regional metamorphism provides critical constraints for unravelling lithosphere evolution and geodynamic settings, especially in an orogenic system. Recently, there has been a debate on the Rodinia-forming Tarimian orogeny within the Greater Tarim block in NW China. The North Wulan terrane, involved in the Paleozoic Qilian orogen, was once part of the Greater Tarim block. This investigation of petrography, whole-rock and mineral geochemistry, phase equilibrium modeling, and in situ monazite U-Pb dating of garnetite, pelitic gneiss, and quartz schist samples from the Statherian–Calymmian unit of the North Wulan terrane provides new constraints on the evolutionary history of the Greater Tarim block at the end of the Mesoproterozoic during the assembly of Rodinia. The studied samples yielded three monazite U-Pb age groups of ca. 1.32 Ga, 1.1 Ga, and 0.45 Ga that are interpreted to be metamorphic in origin. The tectonic significance of the early ca. 1.32 Ga metamorphism is uncertain and may indicate an extensional setting associated with the final breakup of Columbia. The ca. 1.1 Ga low-pressure, high-temperature (low-P/T)–type granulite-facies metamorphism is well preserved and characterized by a clockwise P-T path with a minimum estimation of ∼840–900 °C and ∼7–11 kbar for peak metamorphism, followed by postpeak decompression and cooling. A tectonothermal disturbance occurred at ca. 0.45 Ga, but with limited influence on the preexisting mineral compositions of the studied samples. The characteristics of the metamorphism indicate an arc–back-arc environment with ongoing subduction of oceanic lithosphere at ca. 1.1 Ga. Combined with previous studies, we suggest that the Greater Tarim block probably experienced a prolonged subduction-to-collision process at ca. 1.1–0.9 Ga during the assembly of Rodinia, with a position between western Laurentia and India–East Antarctica.
Geochronology of volcanically associated hydrocarbon charge in the pre-salt carbonates of the Namibe Basin, Angola
Authors: Rochelle-Bates N. , Roberts N.M.W. , Sharp I. , Freitag U. , Verwer K. , Halton A. , Fiordalisi E. , van Dongen B.E. , Swart R. , Ferreira C.H. , Dixon R. , Schröder S.
Published: February 2021

In volcanic rifted margins, the timing of hydrocarbon charge is difficult to predict, but is important in understanding fluid genesis. We investigated whether igneous activity was linked to hydrocarbon charge in the prolific South Atlantic pre-salt petroleum system. To do this, we applied in situ carbonate U-Pb geochronology, a relatively novel tool for dating hydrocarbon migration, to bituminous veins in pre-salt travertines from the rifted onshore Namibe Basin (Angola). To test if fluid flow was synchronous with known volcanic pulses, we also obtained new 40Ar/39Ar geochronology from a nearby volcanic complex. Bitumen is associated with calcite in a first generation of veins and vugs, and with dolomite in younger veins. The dated calcite veins yielded a pooled U-Pb age of 86.2 ± 2.4 Ma, which overlaps the volcanism 40Ar/39Ar age of 89.9 ± 1.8 Ma. The overlapping dates and the localized bitumen occurrence around the dated volcanic center show a clear genetic relationship between Late Cretaceous igneous activity and hydrocarbon charge. The dolomite was dated at 56.8 ± 4.8 Ma, revealing a previously unknown Paleocene/Eocene fluid-flow phase in the basin.
Mineralogical Crystallography: Look in the Past, New Trends, and Highlights
Authors: Pushcharovsky D. Yu.
Published: February 2021

Many urgent problems of modern mineralogical crystallography, to which the papers of this thematic issue of the journal Kristallografiya (Crystallography Reports) are devoted, have been considered. It is shown how the use of advanced physicochemical methods enriches scientific concepts about the real structures of minerals and nature-like compounds, structural conditionality of their physical properties, forms of concentration of chemical elements in terrestrial shells, crystallogenesis conditions, structural transformations in deep geospheres, relationships between structure types, and their interpretations based on modern concepts.
Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials
Authors: Herrett Emily , Williamson Elizabeth , Brack Kieran , Beaumont Danielle , Perkins Alexander , Thayne Andrew , Shakur-Still Haleema , Roberts Ian , Prowse Danielle , Goldacre Ben , van Staa Tjeerd , MacDonald Thomas M , Armitage Jane , Wimborne Jon , Melrose Paula , Singh Jayshireen , Brooks Lucy , Moore Michael , Hoffman Maurice , Smeeth Liam
Published: February 2021

Objective

To establish the effect of statins on muscle symptoms in people who had previously reported muscle symptoms when taking statins.

Design

Series of randomised, placebo controlled n-of-1 trials.

Setting

Primary care across 50 sites in the United Kingdom, December 2016 to April 2018.

Participants

200 participants who had recently stopped or were considering stopping treatment with statins because of muscle symptoms.

Interventions

Participants were randomised to a sequence of six double blinded treatment periods (two months each) of atorvastatin 20 mg daily or placebo.

Main outcome measures

At the end of each treatment period, participants rated their muscle symptoms on a visual analogue scale (0-10). The primary analysis compared symptom scores in the statin and placebo periods.

Results

151 participants provided symptoms scores for at least one statin period and one placebo period and were included in the primary analysis. Overall, no difference in muscle symptom scores was found between the statin and placebo periods (mean difference statin minus placebo −0.11, 95% confidence interval −0.36 to 0.14; P=0.40)). Withdrawals because of intolerable muscle symptoms were 18 participants (9%) during a statin period and 13 (7%) during a placebo period. Two thirds of those completing the trial reported restarting long term treatment with statins.

Conclusions

No overall effect of atorvastatin 20 mg on muscle symptoms compared with placebo was found in participants who had previously reported severe muscle symptoms when taking statins. Most people completing the trial intended to restart treatment with statins. N-of-1 trials can assess drug effects at the group level and guide individual treatment.

Trial registration

ISRCTN30952488
, EUDRACT 2016-000141-31,
NCT02781064
.
Prevalence of non-communicable chronic conditions, multimorbidity and its correlates among older adults in rural Nepal: a cross-sectional study
Authors: Yadav Uday Narayan , Ghimire Saruna , Mistry Sabuj Kanti , Shanmuganathan Selvanaayagam , Rawal Lal B , Harris Mark
Published: February 2021

Objectives

This study’s objectives were to estimate the prevalence of major non-communicable conditions and multimorbidity among older adults in rural Nepal and examine the associated socioeconomic and behavioural risk factors.

Design

This was a community-based cross-sectional study conducted between January and April 2018.

Setting

Rural municipalities of Sunsari and Morang districts in eastern Nepal.

Participants

794 older Nepalese adults, 60 years and older, were recruited using a multistage cluster sampling approach.

Primary outcome measure(s)

Prevalence of four major non-communicable chronic conditions (osteoarthritis, cardiovascular disease, diabetes and chronic obstructive pulmonary disease (COPD) and multimorbidity.

Results

Almost half (48.9%: men 45.3%; women 52.4%) of the participants had at least one of four non-communicable chronic conditions, and 14.6% (men 12.5%; women 16.8%) had two or more conditions. The prevalence of individual conditions included: osteoarthritis—41.7% (men 37.5%; women 45.9%), cardiovascular disease—2.4% (men 2.8%; women 2.0%), diabetes—5.3% (men 6.0%; women 4.6%) and COPD—15.4% (men 13.3%; women 17.5%). In the adjusted model, older adults aged 70–79 years (adjusted OR (AOR): 1.62; 95% CI: 1.04 to 2.54), those from Madhesi and other ethnic groups (AOR: 1.08; 95% CI: 1.02 to 1.72), without a history of alcohol drinking (AOR: 1.53; 95% CI: 1.18 to 2.01) and those physically inactive (AOR: 5.02; 95% CI: 1.47 to 17.17) had significantly higher odds of multimorbidity.

Conclusions

This study found one in seven study participants had multimorbidity. The prevalence of multimorbidity and associated socioeconomic and behavioural correlates need to be addressed by integrating social programmes with health prevention and management at multiple levels. Moreover, a longitudinal study is suggested to understand the temporal relationship between lifestyle predictors and multimorbidity among older Nepalese adults.
Study protocol for investigating the performance of an automated blood test measuring GFAP and UCH-L1 in a prospective observational cohort of patients with mild traumatic brain injury: European BRAINI study
Authors: Richard Marion , Lagares Alfonso , Bondanese Victor , de la Cruz Javier , Mejan Odile , Pavlov Vladislav , Payen Jean-François
Published: February 2021

Introduction

Mild traumatic brain injury (mTBI) is a common cause of clinical consultation in the emergency department. Patients with mTBI may undergo brain CT scans based on clinical criteria. However, the proportion of patients with brain lesions on CT is very low. Two serum biomarkers, glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), have been shown to discriminate patients regarding the presence or absence of brain lesions on initial CT scan when assessed within the first 12 hours after TBI. However, the current technique for measuring serum concentrations of GFAP and UCH-L1 is manual and time consuming, which may hinder its use in routine clinical practice. This study assesses the diagnostic accuracy of an automated assay for the measurement of serum GFAP and UCH-L1 in a cohort of patients with mTBI who received a CT scan as the standard of care.

Methods and analysis

This is a prospective multicentre observational study of 1760 patients with mTBI recruited in France and Spain across 16 participating sites. Adult patients with an initial Glasgow Coma Scale score of 13–15 and a brain CT scan underwent blood sampling within 12 hours after TBI. The primary outcome measure is the diagnostic performance of an automated assay measuring serum concentrations of GFAP and UCH-L1 for discriminating between patients with positive and negative findings on brain CT-scans. Secondary outcome measures include the performance of these two biomarkers in predicting the neurological status and quality of life at 1 week and 3 months after the trauma.

Ethics and dissemination

Ethics approval was obtained by the Institutional Review Board of Sud-Ouest Outre Mer III in France (Re#2019-A01525-52) and Hospital 12 de Octubre in Spain (Re#19/322). The results will be presented at scientific meetings and published in peer-reviewed publications.

Trial registration number

ClinicalTrials.gov:NCT04032509.
Descriptive epidemiology on the trends and sociodemographic risk factors of disease burden in years of life lost due to suicide in South Korea from 2000 to 2018
Authors: Kim Keun A , Kim Young-Eun , Yoon Seok-Jun
Published: February 2021

Objectives

In 2018, South Korea’s suicide mortality rate was 26.59 deaths per 100 000 people; this figure is 2.2 times higher than that of the year 2000, during which 12.22 deaths per 100 000 people were ascribed to suicide. This study aims to observe the trend of disease burden in years of life lost (YLL) due to suicide from 2000 to 2018 in South Korea and investigate the related sociodemographic risk factors.

Design

This quantitative research used secondary data—including claim data, cause of death statistics, life tables and census data—from national health insurance corporation and Statistics Korea. Based on the methodology of Korean National Burden of Disease study, this study used an incidence-based approach to measure YLL.

Results

The total YLL due to suicide during the last two decades was 4 298 886 years; the average YLL per death was 18.65 years. The YLL rate per 100 000 people was 482 (male: 664, female: 300) in 2018, 1.7 times higher than the 387 (male 387, female 183) in 2000. Low education levels and non-marital status were shown to be related to the increase in YLL rate.

Conclusion

These results show the increasing disease burden of suicide in South Korea and suggest the necessity of more in-depth research to analyse correlation and causation with sociodemographic risk factors.
Experiences of healthcare providers during the coronavirus pandemic and its impact on them: protocol for a mixed-methods systematic review
Authors: Xu Na , Lv AiLi , Li TianZi , Li XiaoFeng , Huang Mei , Su Yan
Published: February 2021

Introduction

Frontline healthcare providers are redeployed to areas outside their clinical expertise and assigned high-loading workload to address the surge of patients with each coronavirus outbreak. Their importance in crisis is not in doubt. However, they experienced considerable physical distress and psychological stressors, even leading to psychological illness and infection in this environment. There is an urgent need to accurately, comprehensively and objectively understand their experiences, perceptions and current situation of burnout, post-traumatic stress disorder (PTSD), anxiety, depression, insomnia and coronavirus infection. Therefore, this protocol is to conduct a mixed-methods systematic review to summarise the evidence on the experiences of healthcare providers and impacts of the coronavirus on their psychological status and infection during the pandemics.

Methods

Published studies on experience, perspective, impact, burnout, PTSD, anxiety, depression, insomnia, and infection of healthcare providers with SARS, Middle East respiratory syndrome and COVID-19, and written in English and Chinese will be accepted. Databases (MEDLINE, EMBASE, CENTRAL, Web of Science, PubMed, Psychology Information, WanFang and SinoMed) from inception until 30 July 2020 will be searched. Two reviewers will select, screen, extract data and assess the risk of bias independently. Risk of bias of results will be using the Mixed-Methods Appraisal Tool. Using a convergent integrated approach on qualitative/quantitative studies, we will synthesise qualitative and quantitative data separately. The incidence and number of cases about burnout, PTSD, anxiety, depression, insomnia and coronavirus infection among medical staff will be extracted. Then we will transform quantitative data to synthesise narrative findings. This protocol will be reported per the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines.

Ethics and dissemination

Ethical assessment is not required due to the nature of the proposed systematic review. Findings of our research will be disseminated at conferences related to this field and through publication in peer-reviewed journals.

PROSPERO registration number

CRD42020198506.
Recovery of early postoperative muscle strength after deep neuromuscular block by means of ultrasonography with comparison of neostigmine versus sugammadex as reversal drugs: study protocol for a randomised controlled trial
Authors: Wang Xuan , Li Yingyuan , Huang Chanyan , Xiong Wei , Zhou Qin , Niu Lijun , Xiao Ying
Published: February 2021

Introduction

Despite the use of quantitative neuromuscular monitoring together with the administration of reversal drugs (neostigmine or sugammadex), the incidence of residual neuromuscular blockade defined as a train-of-four ratio (TOFr) <0.9 remains high. Even TOFr >0.9 cannot ensure adequate recovery of neuromuscular function when T1 height is not recovered completely. Thus, a mathematical correction of TOFr needs to be applied because the return of a normal TOFr can precede the return of a normal T1 twitch height. On the other hand, different muscles have different sensitivities to neuromuscular blockade agents; thus, complete recovery of one specific muscle group does not represent complete recovery of all other muscles. Therefore, our study aims to assess the muscle strength recovery of respiratory-related muscle groups by ultrasound and evaluate global strength using handgrip dynamometry in the early postoperative period when TOFr=0.9 and corrected TOFr (cTOFr)=0.9 with comparison of neostigmine versus sugammadex as reversal drugs.

Methods and analysis

This study will be a prospective, single-blinded, randomised controlled trial involving 60 patients with American Society of Anesthesiologists physical status I–II and aged between 18 and 65 years, who will undergo microlaryngeal surgery. We will assess geniohyoid muscle, parasternal intercostal muscle, diaphragm, abdominal wall muscle and handgrip strength at four time points: before anaesthesia, TOFr=0.9, cTOFr=0.9 and 30 min after admission to the post anaesthesia care unit. Our primary objective will be to compare the effects of neostigmine and sugammadex on the recovery of muscle strength of different muscle groups in the early postoperative period when TOFr=0.9 and cTOFr=0.9. The secondary objective will be to observe the difference of muscle strength between the time points of TOFr=0.9 and cTOFr=0.9 to find out the clinical significance of cTOFr >0.9.

Ethics and dissemination

The protocol was reviewed and approved by the Ethics Committee of The First Affiliated Hospital, Sun Yat-sen University. The findings will be disseminated to the public through peer-reviewed scientific journals.

Trial registration number

ChiCTR2000033832.
COVID-19 in a cohort of pregnant women and their descendants, the MOACC-19 study
Authors: Llorca Javier , Lechosa-Muñiz Carolina , Gortazar Pilar , Fernández-Ortiz María , Jubete Yolanda , Cabero Maria J
Published: February 2021

Purpose

The Mother and Child COVID-19 study is a cohort recruiting pregnant women and their children in Cantabria, North of Spain, during COVID-19 pandemic in order to ascertain consequences of SARS-CoV-2 infection on pregnant women and their descendants. This article reports the cohort profile and preliminary results as recruitment is still open.

Participants

Three subcohorts can be identified at recruitment. Subcohort 1 includes women giving birth between 23 March and 25 May 2020; they have been retrospectively recruited and could have been exposed to COVID-19 only in their third trimester of pregnancy. Subcohort 2 includes women giving birth from 26 May 2020 on; they are being prospectively recruited and could have been exposed to COVID-19 in both their second and third trimesters of pregnancy. Subcohort 3 includes women in their 12 week of pregnancy prospectively recruited from 26 May 2020 on; they could have been exposed to COVID-19 anytime in their pregnancy. All women are being tested for SARS-CoV-2 infection using both RT-PCR for RNA detection and ELISA for anti-SARS-CoV-2 antibodies. All neonates are being tested for antibodies using immunochemoluminiscency tests; if the mother is tested positive for SARS-CoV-2 RNA, a nasopharyngeal swab is also obtained from the child for RT-PCR analysis.

Findings to date

As of 22 October, 1167 women have been recruited (266, 354 and 547 for subcohorts 1, 2 and 3, respectively). Fourteen women tested positive to SARS-CoV-2 RNA by the day of delivery. All 14 children born from these women tested negative for SARS-CoV-2 RNA.

Future plans

Children from women included in subcohort 3 are expected to be recruited by the end of 2020. Children will be followed-up for 1 year in order to ascertain the effect that COVID-19 on their development.
Prediction of COVID-19 severity using laboratory findings on admission: informative values, thresholds, ML model performance
Authors: Statsenko Yauhen , Al Zahmi Fatmah , Habuza Tetiana , Gorkom Klaus Neidl-Van , Zaki Nazar
Published: February 2021

Background

Despite the necessity, there is no reliable biomarker to predict disease severity and prognosis of patients with COVID-19. The currently published prediction models are not fully applicable to clinical use.

Objectives

To identify predictive biomarkers of COVID-19 severity and to justify their threshold values for the stratification of the risk of deterioration that would require transferring to the intensive care unit (ICU).

Methods

The study cohort (560 subjects) included all consecutive patients admitted to Dubai Mediclinic Parkview Hospital from February to May 2020 with COVID-19 confirmed by the PCR. The challenge of finding the cut-off thresholds was the unbalanced dataset (eg, the disproportion in the number of 72 patients admitted to ICU vs 488 non-severe cases). Therefore, we customised supervised machine learning (ML) algorithm in terms of threshold value used to predict worsening.

Results

With the default thresholds returned by the ML estimator, the performance of the models was low. It was improved by setting the cut-off level to the 25th percentile for lymphocyte count and the 75th percentile for other features. The study justified the following threshold values of the laboratory tests done on admission: lymphocyte count <2.59×109/L, and the upper levels for total bilirubin 11.9 μmol/L, alanine aminotransferase 43 U/L, aspartate aminotransferase 32 U/L, D-dimer 0.7 mg/L, activated partial thromboplastin time (aPTT) 39.9 s, creatine kinase 247 U/L, C reactive protein (CRP) 14.3 mg/L, lactate dehydrogenase 246 U/L, troponin 0.037 ng/mL, ferritin 498 ng/mL and fibrinogen 446 mg/dL.

Conclusion

The performance of the neural network trained with top valuable tests (aPTT, CRP and fibrinogen) is admissible (area under the curve (AUC) 0.86; 95% CI 0.486 to 0.884; p<0.001) and comparable with the model trained with all the tests (AUC 0.90; 95% CI 0.812 to 0.902; p<0.001). Free online tool at https://med-predict.com illustrates the study results.
Onyx embolization for dural arteriovenous fistulas: a multi-institutional study
Authors: Li Yangchun , Chen Stephanie H , Guniganti Ridhima , Kansagra Akash P , Piccirillo Jay F , Chen Ching-Jen , Buell Thomas , Sheehan Jason P , Ding Dale , Lanzino Giuseppe , Brinjikji Waleed , Kim Louis J , Levitt Michael R , Abecassis Isaac Josh , Bulters Diederik O , Durnford Andrew , Fox W Christopher , Polifka Adam J , Gross Bradley A. , Sur Samir , McCarthy David J , Yavagal Dileep R , Peterson Eric C , Hayakawa Minako , Derdeyn Colin , Samaniego Edgar A , Amin-Hanjani Sepideh , Alaraj Ali , Kwasnicki Amanda , Charbel Fady T , van Dijk J Marc C , Potgieser Adriaan RE , Satomi Junichiro , Tada Yoshiteru , Abla Adib , Phelps Ryan , Du Rose , Lai Pui Man Rosalind , Zipfel Gregory J , Starke Robert M
Published: February 2021

Background

Although the liquid embolic agent, Onyx, is often the preferred embolic treatment for cerebral dural arteriovenous fistulas (DAVFs), there have only been a limited number of single-center studies to evaluate its performance.

Objective

To carry out a multicenter study to determine the predictors of complications, obliteration, and functional outcomes associated with primary Onyx embolization of DAVFs.

Methods

From the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database, we identified patients who were treated for DAVF with Onyx-only embolization as the primary treatment between 2000 and 2013. Obliteration rate after initial embolization was determined based on the final angiographic run. Factors predictive of complete obliteration, complications, and functional independence were evaluated with multivariate logistic regression models.

Results

A total 146 patients with DAVFs were primarily embolized with Onyx. Mean follow-up was 29 months (range 0–129 months). Complete obliteration was achieved in 80 (55%) patients after initial embolization. Major cerebral complications occurred in six patients (4.1%). At last follow-up, 84% patients were functionally independent. Presence of flow symptoms, age over 65, presence of an occipital artery feeder, and preprocedural home anticoagulation use were predictive of non-obliteration. The transverse-sigmoid sinus junction location was associated with fewer complications, whereas the tentorial location was predictive of poor functional outcomes.

Conclusions

In this multicenter study, we report satisfactory performance of Onyx as a primary DAVF embolic agent. The tentorium remains a more challenging location for DAVF embolization, whereas DAVFs located at the transverse-sigmoid sinus junction are associated with fewer complications.
POSITIVE: Perfusion imaging selection of ischemic stroke patients for endovascular therapy
Authors: Mocco J , Siddiqui Adnan H , Fiorella David , Alexander Michael J , Arthur Adam S , Baxter Blaise W , Budzik Ronald F , Froehler Michael T , Hanel Ricardo A , Lena Jonathan , Persaud Steven , Puri Ajit S , Rai Ansaar T , Wintermark Max , Woodward Keith , Zhang Xiangnan , Turk Aquilla
Published: February 2021

Background

The PerfusiOn imaging Selection of Ischemic sTroke patIents for endoVascular thErapy (POSITIVE) trial was designed to evaluate functional outcome in patients with emergent large vessel occlusion (ELVO) presenting within 0–12 hours with pre-specified bifurcated arms of early and late window presentation, who were selected for endovascular thrombectomy with non-vendor specific commercially available perfusion imaging software. Recent trials demonstrating the benefit of thrombectomy up to 16–24 hours following ELVO removed equipoise to randomize late window ELVO patients and therefore the trial was halted.

Methods

Up to 200 patients were to be enrolled in this FDA-cleared, prospective, randomized, multicenter international trial to compare thrombectomy and best medical management in patients with ELVO ineligible for or refractory to treatment with IV tissue plasminogen activator (IV-tPA) selected with perfusion imaging and presenting within 0–12 hours of last seen normal. The primary outcome was 90-day clinical outcome as measured by the raw modified Rankin Scale (mRS) with scores 5 and 6 collapsed (mRS shift analysis).

Results

The POSITIVE trial suspended enrollment with the release of results from the DAWN trial and was stopped after the release of the DEFUSE 3 trial results. Thirty-three patients were enrolled (21 for medical management and 12 for thrombectomy). Twelve of the 33 patients were enrolled in the 6–12 hour cohort. Despite the early cessation, the primary outcome demonstrated statistically significant superior clinical outcomes for patients treated with thrombectomy (P=0.0060). The overall proportion of patients achieving an mRS score of 0–2 was 75% in the thrombectomy cohort and 43% in the medical management cohort (OR 4.00, 95% CI 0.84 to 19.2).

Conclusion

POSITIVE supports the already established practice of delayed thrombectomy for appropriately selected patients presenting within 0–12 hours selected by perfusion imaging from any vendor. The results of the POSITIVE trial are consistent with other thrombectomy trials. The statistically significant effect on functional improvement, despite the small number of patients, reinforces the robust benefits of thrombectomy.

Clinical trial registration

NCT01852201
Confirmatory testing ofNeisseria gonorrhoeaein a sexual health clinic: implications for epidemiology and treatment policy
Authors: Tielemans Myrte , van Westreenen Mireille , Klaassen Corné , Götz Hannelore M
Published: February 2021

Objectives

European guidelines advise the use of dual nucleic acid amplification tests (NAAT) in order to minimise the inappropriate diagnosis ofNeisseria gonorrhoeae(Ng) in urogenital samples from low prevalence areas and in extragenital specimens. In this cross-sectional study, we investigated the effect of confirmatory testing and confirmation policy on the Ng-positivity in a population visiting the sexual health clinic in Rotterdam, the Netherlands.

Methods

Apart from urogenital testing, extragenital (oropharyngeal/anorectal) testing was performed for men who have sex with men (MSM) and according to sexual exposure for women and heterosexual men. Ng detection using NAAT was performed using BD Viper and for confirmatory testing BD MAX. Sexual transmitted infection consultation data were merged with diagnostic data from August 2015 through May 2016.

Results

In women (n=4175), oral testing was performed in 84% and 22% were tested anally. In MSM (n=1828), these percentages were 97% and 96%, respectively. Heterosexual men (n=3089) were tested urogenitally. After confirmatory testing, oropharyngeal positivity rates decreased from 7.3% (95% CI 6.5 to 8.2) to 1.5% (95% CI 1.1 to 1.8) in women and from 13.9% (95% CI 12.3 to 15.5) to 5.4% (95% CI 4.3 to 6.4) in MSM. Anorectal positivity rates decreased from 2.6% (95% CI 1.6 to 3.7) to 1.8% (95% CI 0.9 to 2.6) in women and from 9.3% (95% CI 7.9 to 10.7) to 7.2% (95% CI 6.0 to 8.5) in MSM. Urogenital Ng-positivity rate ranged between 3.0% and 4.4% and after confirmation between 2.3% and 3.9%. When confirming oropharyngeal samples, Ng-positivity was 3.8% in women, 3.0% in heterosexual men and 12.5% in MSM. Additional confirmation of urogenital and anorectal samples led to 3.0% Ng positivity in women, 2.7% in heterosexual men and 11.4% in MSM.

Conclusions

Confirmation of urogenital and anorectal samples reduced the Ng-positivity rates, especially for women. However, as there is no gold standard for the confirmation of Ng infection, the dilemma within public health settings is to choose between two evils: missing diagnoses or overtreatment. In view of the large decrease in oropharyngeal positivity, confirmation Ng-positivity in oropharyngeal samples remains essential to avoid unnecessary treatment.
Factors associated with interest in a long-acting HIV regimen: perspectives of people living with HIV and healthcare providers in four European countries
Authors: Akinwunmi Babatunde , Buchenberger Daniel , Scherzer Jenny , Bode Martina , Rizzini Paolo , Vecchio Fabio , Roustand Laetitia , Nachbaur Gaelle , Finkielsztejn Laurent , Chounta Vasiliki , Van de Velde Nicolas
Published: February 2021

Objectives

A novel long-acting regimen (LAR) of cabotegravir and rilpivirine for HIV treatment requires dosing every 2 months instead of daily. We assessed what proportion of people living with HIV and physicians would be interested in trying and offering LAR respectively and why.

Methods

688 people living with HIV on treatment, and 120 HIV physicians completed web-based surveys in Germany, Italy, the UK and France during 2019. Balanced description of a hypothetical LAR regarding efficacy, administration and possible side effects were provided. The hypothetical long-acting injections were assumed to be cost-neutral to current daily oral antiretrovirals. Interest of people living with HIV intrying(‘very’/’highly’) and physicians’ willingness tooffer(‘definitely’/’probably’) this LAR in different situations, with perceived benefits/concerns was measured.

Results

Of people living with HIV, 65.8% were interested in trying LAR. The majority (~80%–90%) of those with unmet needs felt LAR would help, including those with strong medical needs (malabsorption and interfering gastrointestinal conditions), suboptimal adherence, confidentiality/privacy concerns and emotional burden of daily dosing. Of physicians, percentage willing to offer LAR varied situationally: strong medical need (dysphagia, 93.3%; malabsorption, 91.6%; interfering gastrointestinal issues, 90.0%; central nervous system disorders, 87.5%); suboptimal adherence (84.2%); confidentiality/privacy concerns (hiding medications, 86.6%) and convenience/lifestyle (84.2%). People living with HIV liked LAR for not having to carry pills when travelling (56.3%); physicians liked the increased patient contact (54.2%). Furthermore, 50.0% of people living with HIV perceived LAR would minimise transmission risk and improve their sexual health. The most disliked attribute was scheduling appointments (37.2%) and resource constraints (57.5%) for people living with HIV and physicians, respectively. Physicians estimated 25.7% of their patients would actually switch.

Conclusion

Providers and people living with HIV viewed the described LAR as addressing several unmet needs. Alternative treatment routes and especially LAR may improve adherence and quality of life.