bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical Development and Validation of Clinical Prediction Models
Authors: Staffa Steven J. , Zurakowski David
Published: July 2021

Clinical prediction models in anesthesia and surgery research have many clinical applications including preoperative risk stratification with implications for clinical utility in decision-making, resource utilization, and costs. It is imperative that predictive algorithms and multivariable models are validated in a suitable and comprehensive way in order to establish the robustness of the model in terms of accuracy, predictive ability, reliability, and generalizability. The purpose of this article is to educate anesthesia researchers at an introductory level on important statistical concepts involved with development and validation of multivariable prediction models for a binary outcome. Methods covered include assessments of discrimination and calibration through internal and external validation. An anesthesia research publication is examined to illustrate the process and presentation of multivariable prediction model development and validation for a binary outcome. Properly assessing the statistical and clinical validity of a multivariable prediction model is essential for reassuring the generalizability and reproducibility of the published tool.
A Quality Improvement Project to Increase Frequency of Skin-to-Skin Contact for Extreme Low-Birth-Weight Infants in the Neonatal Intensive Care Unit
Authors: Nation Helen , Sanlorenzo Lauren , Lebar Kiersten , Brandon Debra
Published: July 2021

Benefits of skin-to-skin contact (SSC) are documented but often delayed in the extremely preterm population due to medical complexity and staff misconceptions about safety. This quality improvement initiative was designed to increase SSC utilization among infants born before 29 weeks' gestation regardless of respiratory support by addressing nursing barriers inhibiting SSC. A pre-/postsurvey evaluated comfort level performing and perceived barriers to SSC utilization. Implementation consisted of an updated unit-specific SSC protocol and tailored education specific to identified barriers. Evaluation included SSC rates and maternal human milk usage in the first 30 days of life. In total, 81 patients (22-28 weeks, 370-1410 g) were included. SSC rates ranged from 3.3% to 17.7% at baseline and increased to 33.2% to 39.1% postintervention. Maternal human milk utilization increased above target (≥75%) postintervention for days 7 and 14, but declined towards baseline on days 21 and 30. A statistically significant increase was observed in nursing comfort level when performing SSC for intubated infants as well as infants with a peripherally inserted central catheter or umbilical venous catheter. SSC rates increased with infants younger than 29 weeks requiring intubation and central line management, possibly as a result of greater nursing comfort surrounding with SSC.
Breastfeeding as a Quality Measure
Authors: Jolles Diana R. , Hoehn-Velasco Lauren
Published: July 2021

The purpose of this study is to explore the National Quality Strategy (NQS) levers (measurement and feedback, public reporting, learning and technical assistance, and certification) on state and national breastfeeding performance. The research evaluates the NQS levers of measurement and feedback and public reporting using secondary data analysis of publicly reported data from the National Immunization Survey and the Centers for Disease Control and Prevention Breastfeeding Report Cards between 2008 and 2018, the latest years available. Linear regression explores the association between the prevalence of state-level Baby-Friendly hospitals and state-level breastfeeding rates. Subsequent analyses use event study to test whether state-level Baby-Friendly hospital adoption is associated with higher breastfeeding rates. A 10% increase in Baby-Friendly hospitals at the state level is associated with increased population breastfeeding rates by nearly 5% and a decrease in early formula use (before 2 days of life) by 2% to 9%. Breastfeeding increased by 2% to 5% in the first 2 years following state-level Baby-Friendly initiatives, with subsequent increases up to 10% in the next 4 years. The National Quality Strategy levers of measurement and public reporting combined with certification and learning and technical assistance are associated with increases in exclusive breastfeeding, a national quality metric.
Association of Delivery Outcomes With the Number of Childbirth Education Sessions
Authors: Vanderlaan Jennifer , Sadler Christen , Kjerulff Kristen
Published: July 2021

The objective of this study was to determine whether childbirth education conducted over 3 or more sessions is more effective than courses conducted over 1 or 2 sessions. This was a secondary analysis of 2853 participants in a longitudinal study of women recruited during their first pregnancy. Data on childbirth education attendance were collected during the 1-month postpartum interview. The Kruskal–Wallis test for ranks was used for univariate analysis by the number of class sessions, and logistic regression was used to compare no education with any childbirth education, single-session, 2-session, and 3-or-more-session courses. Primary outcomes included induction of labor, cesarean delivery, use of pain medication, and shared decision-making. Attending 3 or more education sessions was associated with a decreased risk of planned cesarean delivery and increased shared decision-making. Attending any childbirth education was associated with lower odds of using pain medication in labor, reduced odds of planned cesarean delivery, and increased shared decision-making. Childbirth education was not associated with induction of labor. Childbirth education can be provided over 3 or more sessions. This finding can be used to develop evidence-based childbirth education programs.
Perinatal Quality and Equity—Indicators That Address Disparities
Authors: Rochin Elizabeth , Reed Kaitlin , Rosa Andrew , Guida Wendy , Roach John , Boyle Sandra , Kohli Nishi , Webb Ann
Published: July 2021

There is tremendous attention in maternal and neonatal disparities, particularly disparities of race and ethnicity and subsequent outcomes that continue despite calls to action. The literature has offered potential opportunities for exploring data related to racial and ethnic disparities, including the utilization of a race and ethnicity reporting dashboard. This article reviews definitions of perinatal quality and disparity and provides insight into the development of a nationally targeted race and ethnicity dashboard. This quarterly dashboard provides hospitals with specific key metric outcomes through the lens of race and ethnicity, provides a national benchmark for comparison, and creates a data platform for team exploration and comprehensive review of findings. An overview of the development of the dashboard is provided, and the selection of key maternal and neonatal metrics is reviewed. In addition, recommendations for data science strategic planning and nursing's role in metric development, analysis, and utilization are offered and key steps in accelerating disparity data into everyday clinical care are discussed.
Part 2: Theoretical Intakes of Modern-Day Paleo Diets
Authors: Karlsen Micaela C. , Livingston Kara A. , Agoulnik Dasha , Miki Akari , Lichtenstein Alice H. , Gilhooly Cheryl H. , Folta Sara C. , Economos Christina D. , McKeown Nicola M.
Published: July 2021

Background

The Paleo diet is a popular dietary pattern based on interpretation of evolutionary diets.

Objective

The aim of this study was to assess the relative dietary quality of theoretical, modern-day Paleo meal plans, in comparison with national nutrition guidance.

Methods

This analysis used data from the Adhering to Dietary Approaches for Personal Taste survey. Survey respondents who self-identified as following a Paleo diet (N = 925) reported their top sources of food and nutrition information, and a random sample (n = 200) were selected for analysis. Five days of theoretical meal plans identified from each of the top 6 sources cited by Paleo participants (for a total of 30 days of meal plans) as well as 21 days of theoretical MyPlate meal plans, were analyzed using the Nutrition Data System for Research. Food and nutrient levels of Paleo meal plans were compared with the Dietary References Intakes and MyPlate meal plans.

Results

Paleo meal plans contain no identifiable refined grains or added sugars and have higher fruit and vegetable intakes than MyPlate meal plans. However, Paleo meal plans exceeded recommended levels of saturated fat (19% kcal/day), resulting in low unsaturated-saturated fat ratios, and did not meet the Dietary References Intakes for total carbohydrate, fiber, calcium, and potassium.

Conclusion

Although certain aspects of promoted Paleo meal plans offer improvements over typical American intakes, Paleo diets should be approached with caution, particularly because of the potential for increased cardiovascular risk owing to low unsaturated/saturated fat ratios. Future research should compare actual intakes with theoretical targets.
Diet and Body Composition of Soccer (Football) Players and Referees in Iran
Authors: Jibril Aliyu Tijani , Beba Mohammad , Shab-Bidar Sakineh , Seifbarghi Tohid , Djafarian Kurosh
Published: July 2021

We evaluated the associations of micronutrient adequacy (measured by the mean adequacy ratio of intakes to nutrient recommendations) and dietary acid load with body composition in 218 football (soccer) players and referees in Iran to provide insights that might help to optimize nutrition and overall performance. Despite the alkaline nature of their diets, there was no association between dietary acid load indices and body composition, and the mean adequacy ratio was positively associated only with percentage body fat (β = .17, P = .01). Further studies with larger sample sizes and longer durations are recommended.
Individual Preparedness for Distant Wildfires and the Delta Variant in the United States: A Survey of 2,250 US Residents
Authors: Srikrishna Devabhaktuni
Published: July 2021

Background

COVID-19 virus travels in the air and collects indoors through tiny particles from exhaled breath, and remains a growing concern globally especially since case studies of vaccine breakthrough infections are being reported. Last year’s wildfires resulted in the worst air quality on record in the Western US due to toxic wildfire smoke (PM 2.5 pollution) traveling from distant wildfires and this year can potentially be even worse due to extremely dry conditions. Aerosol precautions such as high-filtration (Hi-Fi) masks and HEPA air purifiers are useful to effectively reduce inhalation of most of these toxic aerosols. Whereas the lack of fit or filtration in a mask or use of an air purifier of insufficient size (capacity) for the room can inadvertently render these precautions ineffective. Here we investigate the public’s concerns about wildfires and the COVID-19 variants (e.g. delta), their use of aerosol precautions, and whether these are being done in an effective manner.

Methods

We conducted a national survey of 2,250 US residents in order to understand public concerns about airborne threats and their usage of airborne (aerosol) precautions.

Results

We find over 66% of US residents surveyed are worried about inhaling COVID-19 and its variants, and 52% are worried about toxic wildfire particles in the air. In the mountain and pacific regions the latter rises to 73%. Only a quarter are using masks with higher filtration and high level of fit (or Hi-Fi masks e.g. N95 or similar such as elastomeric N95 or KF94). Two-thirds are still using loose-fitting cloth or surgical masks. Just over 40% of respondents report using air purifiers at home, and of this group only 40% use it in their bedroom where they sleep. Of those using air purifiers, the majority said they chose the size of their air purifier based on “most popular” models, “recommendations,” or “reviews.” However, of those using air purifiers only 42% reported doing a calculation (or using a calculator) to estimate the right size of air purifier needed for the room they are using it in. Notably, a much higher percentage of people (than average) reported use of Hi-Fi masks and home air purifiers in certain occupations such as doctors, healthcare, first responders, public safety, engineering, military, and construction.

Conclusion

National survey data suggests most US residents are worried about wildfire smoke and Covid variants (e.g. delta variant) but a majority are not prepared for it. Preparation with aerosol precautions will also be useful for future pandemics and national biodefense.
Emergence and spread of a B.1.1.28-derived P.6 lineage with Q675H and Q677H Spike mutations in Uruguay
Authors: Rego Natalia , Salazar Cecilia , Paz Mercedes , Costábile Alicia , Fajardo Alvaro , Ferrés Ignacio , Perbolianachis Paula , Fernández-Calero Tamara , Noya Veronica , Machado Matias R. , Arce Rodrigo , Arleo Mailen , Possi Tania , Reyes Natalia , Noel Bentancor María , Lizasoain Andrés , Bortagaray Viviana , Moller Ana , Chappos Odhille , Nin Nicolas , Hurtado Javier , Duquía Melissa , González Belén , Griffero Luciana , Méndez Mauricio , Pía Techera Ma , Zanetti Juan , Rivera Bernardina , Maidana Matías , Alonso Martina , Alonso Cecilia , Medina Julio , Albornoz Henry , Colina Rodney , Bello Gonzalo , Moreno Pilar , Moratorio Gonzalo , Iraola Gregorio , Spangenberg Lucía
Published: July 2021

Uruguay was able to control the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. Herein we analyzed the country-wide genetic diversity of SARS-CoV-2 between November, 2020 and April, 2021. Our findings identified that the most prevalent viral variant during late 2020 was a B.1.1.28 sublineage carrying mutations Q675H+Q677H in the viral Spike, now designated as lineage P.6. This new lineage P.6 probably arose around November 2020, in Montevideo, Uruguay’s capital department and rapidly spread to other Uruguayan departments, with evidence of further local transmission clusters, also spread sporadically to the USA and Spain. The Q675H and Q677H mutations are in the proximity of the polybasic cleavage site at the S1/S2 boundary and also arose independently in many SARS-CoV-2 lineages circulating worldwide. Although the lineage P.6 was replaced by the Variant of Concern (VOC) P.1 as the predominant viral strain in Uruguay since April 2021, the monitoring of the concurrent emergence of Q675H+Q677H in VOCs should be of worldwide interest.
COVID-19 outcomes in hospitalized puerperal, pregnant, and neither pregnant nor puerperal women: a population study
Authors: Serra Fabiano Elisei , Francisco Rossana Pulcineli Vieira , de Rossi Patricia , de Lourdes Brizot Maria , Rodrigues Agatha Sacramento
Published: July 2021

Objective

To compare hospitalized reproductive age women with COVID-19 who were pregnant, puerperal, or neither one nor the other in terms of demographic and clinical characteristics and disease progression using Brazilian epidemiological data.

Methods

A retrospective analysis of the records of the Information System of the Epidemiological Surveillance of Influenza of the Health Ministry of Brazil was performed. It included the data of female patients aged 10 to 49 years hospitalized because of severe COVID-19 disease (RT-PCR+ for SARS-CoV-2), from February17, 2020 to January 02, 2021.They were separated into 3 groups: pregnant, puerperal, and neither pregnant nor puerperal. General comparisons and then adjustments for confounding variables (propensity score matching [PSM]) were made, using demographic and clinical characteristics, disease progression (admission to the intensive care unit [ICU] and invasive or noninvasive ventilatory support), and outcome (cure or death). Deaths were analyzed in each group according to comorbidities, invasive or noninvasive ventilatory support, and admission to the ICU.

Results

As many as 40,640 reproductive age women hospitalized for COVID-19 were identified: 3,372 were pregnant, 794 were puerperal, and 36,474 were neither pregnant nor puerperal. Groups were significantly different in terms of demographic data and comorbidities. Pregnant and puerperal women were less likely to be symptomatic than the women who were neither one nor the other. Pregnant women, however, had a higher frequency of cough, anosmia, and ageusia. Puerperal women had a worse prognosis than pregnant women with respect to admission to the ICU, invasive ventilatory support, and death.

Conclusion

Puerperal women were at a higher risk for serious outcomes (need for the ICU, need for invasive and noninvasive ventilatory support, and death) than pregnant women.
Can Vaccine Prioritization Reduce Disparities in Covid-19 Burden for Historically Marginalized Populations?
Authors: Rosenstrom Erik , Mele Jessica , Ivy Julie , Mayorga Maria , Patel Mehul , Lich Kristen Hassmiller , Johnson Karl , Delamater Paul , Keskinocak Pinar , Boyce Ross , Smith Raymond , Swann Julie L.
Published: July 2021

1.

Importance

Nationally stated goals for distributing SARS-CoV-2 vaccines included to reduce COVID-19 mortality, morbidity, and inequity using prioritization groups. However, the impact of these prioritization strategies is not well understood, particularly their effect on health inequity in COVID-19 burden for historically marginalized racial and ethnic populations.

Objective

To assess the impact of vaccination prioritization and operational strategies on disparities in COVID-19 burden among historically marginalized populations, and on mortality and morbidity by race and ethnicity.

Design

We use an agent-based simulation model of North Carolina to project SARS-CoV-2 infections and COVID-19-associated deaths (mortality), hospitalizations (morbidity), and cases over 18 months (7/1/2020-12/31/2021) with vaccine distribution beginning 12/13/2020 to frontline medical and people 75+, assuming initial uptake similar to influenza vaccine. We study two-stage subsequent prioritization including essential workers (“essential”), adults 65+ (“age”), adults with high-risk health conditions, HMPs, or people in low income tracts, with eligibility for the general population in the third stage. For age-essential and essential-age strategies, we also simulated maximal uptake (100% for HMP or 100% for everyone), and we allowed for distribution to susceptible-only people.

Results

Prioritizing Age then Essential had the largest impact on mortality (2.5% reduction from no prioritization); Essential then Age had the lowest morbidity and reduced infections (4.2% further than Age-Essential) without significantly impacting mortality. Under each prioritization scenario, the age-adjusted mortality burden for HMPs is higher (e.g., 33.3-34.1% higher for the Black population, 13.3%-17.0% for the Hispanic population) compared to the White population, and the gap grew under some prioritizations. In the Age-Essential strategy, the burden on HMPs decreases only when uptake is increased to 100% in HMPs. However, the Black population still had the highest mortality rate even with the Susceptible-Only distribution.

Conclusions and Relevance

Simulation results show that prioritization strategies have differential impact on mortality, morbidity, and disparities overall and by race and ethnicity. If prioritization schemes were not paired with increased uptake in HMPs, disparities did not improve and could worsen. Although equity was one of the tenets of vaccine distribution, the vaccination strategies publicly outlined are insufficient to remove and may exacerbate disparities between racial and ethnic groups, thus targeted strategies are needed for the future.
Leveraging video data from a digital smartphone autism therapy to train an emotion detection classifier
Authors: Hou Cathy , Kalantarian Haik , Washington Peter , Dunlap Kaiti , Wall Dennis P.
Published: July 2021

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting one in 40 children in the United States and is associated with impaired social interactions, restricted interests, and repetitive behaviors. Previous studies have demonstrated the promise of applying mobile systems with real-time emotion recognition to autism therapy, but existing platforms have shown limited performance on videos of children with ASD. We propose the development of a new emotion classifier designed specifically for pediatric populations, trained with images crowdsourced from an educational mobile charades-style game: Guess What?. We crowdsourced the acquisition of videos of children portraying emotions during remote game sessions of Guess What? that yielded 6,344 frames from fifteen subjects. Two raters manually labeled the frames with four of the Ekman universal emotions (happy, scared, angry, sad), a “neutral” class, and “n/a” for frames with an indeterminable label. The data were pre-processed, and a model was trained with a transfer-learning and neural-architecture-search approach using the Google Cloud AutoML Vision API. The resulting classifier was evaluated against existing approaches (Microsoft’s Azure Face API and Amazon Web Service’s Rekognition) using the standard metrics of F1 score. The resulting classifier demonstrated superior performance across all evaluated emotions, supporting our hypothesis that a model trained with a pediatric dataset would outperform existing emotion-recognition approaches for the population of interest. These results suggest a new strategy to develop precision therapy for autism at home by integrating the model trained with a personalized dataset to the mobile game.
Influence of social determinants of health and county vaccination rates on machine learning models to predict COVID-19 case growth in Tennessee
Authors: Wylezinski Lukasz S. , Harris Coleman R. , Heiser Cody N. , Gray Jamieson D. , Spurlock Charles F.
Published: July 2021

The SARS-CoV-2 (COVID-19) pandemic has exposed health disparities throughout the United States, particularly among racial and ethnic minorities. As a result, there is a need for data-driven approaches to pinpoint the unique constellation of clinical and social determinants of health (SDOH) risk factors that give rise to poor patient outcomes following infection in US communities.

We combined county-level COVID-19 testing data, COVID-19 vaccination rates, and SDOH information in Tennessee. Between February-May 2021, we trained machine learning models on a semi-monthly basis using these datasets to predict COVID-19 incidence in Tennessee counties. We then analyzed SDOH data features at each time point to rank the impact of each feature on model performance.

Our results indicate that COVID-19 vaccination rates play a crucial role in determining future COVID-19 disease risk. Beginning in mid-March 2021, higher vaccination rates significantly correlated with lower COVID-19 case growth predictions. Further, as the relative importance of COVID-19 vaccination data features grew, demographic SDOH features such as age, race, and ethnicity decreased while the impact of socioeconomic and environmental factors, including access to healthcare and transportation, increased.

Incorporating a data framework to track the evolving patterns of community-level SDOH risk factors could provide policymakers with additional data resources to improve health equity and resilience to future public health emergencies.
DNA methylation patterns associated with cyanogenic cassava exposure and konzo in Sub-Saharan Africa
Authors: Kocher Kristen , Bhattacharya Surajit , Bramble Matthew S. , Okitundu-Luwa Daniel , Ngoyi Dieudonne Mumba , Tshala-Katumbay Desire , Vilain Eric
Published: July 2021

Main Text

Konzo, a disease characterized by sudden, irreversible spastic paraparesis, affecting up to 10% of the population in some regions of Sub-Saharan Africa during outbreaks and is strongly associated with dietary exposure to cyanogenic bitter cassava. The molecular mechanisms underlying the development of konzo, remain largely unknown. Here, through an analysis of 16 individuals with konzo and matched healthy controls from the same outbreak zones, we identified 117 differentially methylated loci involved in numerous biological processes that may identify cyanogenic- sensitive regions of the genome, providing the first study of epigenomic alterations associated with sub-lethal cyanide exposure and a clinical phenotype.
Identification of muscle weakness in older adults from normalized lower and upper limbs strength
Authors: Abdalla Pedro Pugliesi , Bohn Lucimere , Lopes da Silva Leonardo Santos , dos Santos André Pereira , Tasinafo Junior Marcio Fernando , Rossini Venturini Ana Claudia , dos Santos Carvalho Anderson , Gomez David Martinez , Mota Jorge , Lopes Machado Dalmo Roberto
Published: July 2021

Introduction

Weakness is a natural age-related condition meaning the loss of muscle strength that impairs older adults’ mobility and quality of life. Because the relationship between muscle strength and body-size variables is non-linear, weakness is misclassified in older adults with extreme body size (e.g., light, short, heavy, or tall). This misclassification can be overcome using the allometric approach.

Objectives

To propose cut-off points for older adults’ weakness for upper and lower limbs muscle strength normalized by body size with the ratio standard and allometric scaling.

Methods

Ninety-four community-dwelling older adults (69.1% women) were assessed for 49 body-size variables (anthropometry, body composition and body indexes), handgrip strength (HGS), one maximum repetition measurement for knee extensors (1RMknee extensors), isokinetic knee extension peak torque at 60°/s (knee extensionPT60°/s), and six-minute walk test (6MWT). Ratio standard (muscle strength/body size) and allometric scaling (muscle strength/body sizeb; when b is the allometric exponent) were applied for body-size variables that significantly were correlated with HGS, 1RMknee extensors and knee extensionPT60°/s. Cut-off points were computed based on ROC curve and Youden index. When there was mobility limitation (6MWT<400m) cut-off were computed according to sex.

Results

Absolute HGS, 1RMknee extensors and knee extensionPT60°/s cut-off points were not adequate because they were associated with body size (r>0.30). But it was corrected with muscle strength normalization according to body size-variables: HGS (n=1); 1RMknee extensors (n=24) and knee extensionPT60°/s (n=24). The best cut-off points, with the highest area under the curve (AUC), were found after normalization for men: HGS/forearm circumference (1.33 kg/cm, AUC=0.74), 1RMknee extensors/triceps skinfold (4.22 kg/mm, AUC=0.81), and knee extensionPT60°/s/body mass*height0.43 (13.0 Nm/kg*m0.43, AUC=0.94); and for women: HGS/forearm circumference (1.04 kg/cm, AUC=0.70), 1RMknee extensors/body mass (0.54 kg/kg, AUC=0.76); and knee extensionPT60°/s/body mass0.72 (3.14 Nm/kg0.72; AUC=0.82).

Conclusion

Normalization removes the effect of extreme body size on muscle strength and improves the accuracy to identify weakness at population level, reducing the risk of false-positive cases.

Highlights

This study proposed a new approach to identify muscle weakness in older adults based on upper and lower limbs muscle strength normalized by body size (ratio standard and allometry).

The identification of functional limitation is more precise when procedures of muscle strength normalization is applied.
Monitoring COVID-19 spread in Prague local neighborhoods based on the presence of SARS-CoV-2 RNA in wastewater collected throughout the sewer network
Authors: Zdenkova Kamila , Bartackova Jana , Cermakova Eliska , Demnerova Katerina , Dostalkova Alzbeta , Janda Vaclav , Novakova Zuzana , Rumlova Michaela , Ambrozova Jana Rihova , Skodakova Klara , Swierczkova Iva , Sykora Petr , Vejmelkova Dana , Wanner Jiri , Bartacek Jan
Published: July 2021

Many reports have documented that the presence of SARS-CoV-2 RNA in the influents of municipal wastewater treatment plants (WWTP) correlates with the actual epidemic situation in a given city. However, few data have been reported thus far on measurements upstream of WWTPs, i.e. throughout the sewer network. In this study, the monitoring of the presence of SARS-CoV-2 RNA in Prague wastewater was carried out at selected locations of the Prague sewer network from August 2020 through May 2021. Various locations such as residential areas of various sizes, hospitals, city center areas, student dormitories, transportation hubs (airport, bus terminal), and commercial areas were monitored together with four of the main Prague sewers. The presence of SARS-CoV-2 RNA was determined by reverse transcription – multiplex quantitative polymerase chain reaction (RT-mqPCR) after the precipitation of nucleic acids with PEG8000 and RNA isolation with TRIzol™ Reagent. The number of copies of the gene encoding SARS-CoV-2 nucleocapsid (N1) per liter of wastewater was compared with the number of officially registered COVID-19 cases in Prague. Although the data obtained by sampling wastewater from the major Prague sewers were more consistent than those obtained from the small sewers, the correlation between wastewater-based and clinical-testing data was also good for the residential areas with more than 1 000 registered inhabitants. It was shown that monitoring SARS-CoV-2 RNA in wastewater sampled from small sewers could identify isolated occurrences of COVID-19-positive cases in local neighborhoods. This can be very valuable while tracking COVID-19 hotspots within large cities.

Highlights

SARS-CoV-2 RNA presence was measured at 24 locations in the Prague sewer network

Residential areas (100–13 000 inhab.), transport hubs, hospitals etc. were included

Consistent wastewater monitoring by RT-mqPCR took place from August 2020 – May 2021

The sampling of major Prague sewers correlated well with clinical-based data

Grab samples can identify COVID-19 hotspots in local neighborhoods

Graphical abstract
Features importance in seizure classification using scalp EEG reduced to single timeseries
Authors: Naze Sébastien , Tang Jianbin , Kozloski James R. , Harrer Stefan
Published: July 2021

Seizure detection and seizure-type classification are best performed using intra-cranial or full-scalp electroencephalogram (EEG). In embedded wearable systems however, recordings from only a few electrodes are available, reducing the spatial resolution of the signals to a handful of timeseries at most. Taking this constraint into account, we tested the performance of multiple classifiers using a subset of the EEG recordings by selecting a single trace from the montage or performing a dimensionality reduction over each hemispherical space. Our results support that Random Forest (RF) classifiers lead most ef-ficient and stable classification performances over Support Vector Machines (SVM). Interestingly, tracking the feature importances using permutation tests reveals that classical EEG spectrum power bands display different rankings across the classifiers: low frequencies (delta, theta) are most important for SVMs while higher frequencies (alpha, gamma) are more relevant for RF and Decision Trees. We reach up to 94.3% ∓ 5.3% accuracy in classifying absence from tonic-clonic seizures using state-of-art sampling methods for unbalanced datasets and leave-patients-out fold cross-validation policy.
Right Ventricular Dysfunction in Ventilated Patients with COVID-19 (COVID-RV)
Authors: McCall Philip , Willder Jennifer , Stanley Bethany , Messow Claudia-Martina , Allan John , Gemmell Lisa , Puxty Alex , Strachan Dominic , Berry Colin , Shelley Ben
Published: July 2021

Purpose

COVID-19 is associated with cardiovascular complications, with right ventricular dysfunction (RVD) commonly reported. The combination of acute respiratory distress syndrome (ARDS), injurious invasive ventilation, micro/macro thrombi and the potential for direct myocardial injury create conditions where RVD is likely to occur. No study has prospectively explored the prevalence of RVD, and its association with mortality, in a cohort requiring mechanical ventilation.

Methods

Prospective, multi-centre, trans-thoracic echocardiographic, cohort study of ventilated patients with COVID-19 in Scottish intensive care units. RVD was defined as the presence of severe RV dilatation and interventricular septal flattening. To explore role of myocardial injury, high sensitivity troponin and N-terminal pro B-type natriuretic peptide (NT-proBNP) were measured in all patients.

Results

One hundred and twenty-one patients were recruited to COVID-RV, 118 underwent imaging and it was possible to determine the primary outcome in 112. RVD was present in seven (6.2% [95%CI; 2.5%, 12.5%]) patients. Thirty-day mortality was 85.7% in those with RVD, compared to 44.8% in those without (p=0.051). Patients with RVD were more likely to have; pulmonary thromboembolism (p<0.001), higher plateau pressure (p=0.048), lower dynamic compliance (p=0.031), higher NT-proBNP (p<0.006) and more frequent abnormal troponin (p=0.048). Abnormal NT-proBNP (OR 4.77 [1.22, 21.32], p=0.03) and abnormal Troponin (16.54 [4.98, 67.12], p<0.001) independently predicted 30-day mortality.

Conclusion

COVID-RV demonstrates a prevalence of RVD in ventilated patients with COVID-19 of 6.2% and is associated with a mortality of 85.7%. Association is observed between RVD and each of the aetiological domains of; ARDS, ventilation, micro/macro thrombi and myocardial injury.
Prospective examination of mental health in university students during the COVID-19 pandemic
Authors: Jia Ru , Knight Holly , Ayling Kieran , Coupland Carol , Corner Jessica , Denning Chris , Ball Jonathan , Bolton Kirsty , Morling Joanne R , Figueredo Grazziela , Morris David Ed , Tighe Patrick , Villalon Armando , Blake Holly , Vedhara Kavita
Published: July 2021

Background

The impact of changing social restrictions on the mental health of students during the COVID-19 pandemic warrants exploration.

Aims

To prospectively examine changes to university students’ mental health during the pandemic.

Methods

Students completed repeated online surveys at three time points (October 2020 (baseline), February 2021, March 2021) to explore relationships between demographic and psychological factors (loneliness and positive mood) and mental health outcomes (depression, anxiety, and stress).

Results

A total of 893 students participated. Depression and anxiety levels were higher at all timepoints than pre-pandemic normative data (p<.001). Scores on all mental health measures were highest in February, with depression and anxiety remaining significantly higher in March than baseline. Female students and those with previous mental health disorders were at greatest risk of poor mental health outcomes. Lower positive mood and greater loneliness at baseline were associated with greater depression and anxiety at follow-ups. Baseline positive mood predicted improvement of depression and anxiety at follow-ups.

Conclusion

Depression and anxiety were significantly higher than pre-pandemic norms, with female students and those with previous mental health difficulties being at greatest risk. Given these elevated rates, universities should ensure adequate support is available to meet potentially increased demand for services.
Amplitude-integrated EEG amplitudes differ between wakefulness and sleep states in children
Authors: Löffelhardt Verena T. , Marina Adela Della , Greve Sandra , Müller Hanna , Felderhoff-Müser Ursula , Dohna-Schwake Christian , Bruns Nora
Published: July 2021

Introduction

Interpretation of pediatric amplitude-integrated EEG (aEEG) is hindered by the lack of knowledge on physiological background patterns in children. The aim of this study was to assess the amplitudes and bandwidths of background patterns during wakefulness and sleep in children from long-term EEGs.

Methods

Forty long-term EEGs from patients < 18 years of age without or only solitary interictal epileptiform discharges were converted into aEEGs. Upper and lower amplitudes (µV) of the C3 – C4, P3 – P4, C3 – P3, C4 – P4, and Fp1 – Fp2 channels were measured during wakefulness and sleep. Bandwidths (BW, µV) were calculated, and sleep states assessed during the episodes of interest. A sensitivity analysis excluded patients who received antiepileptic drugs.

Results

Median age was 9.9 years (interquartile range 6.1 – 14.7). All patients displayed continuous background patterns. Amplitudes and BW differed between wakefulness (C3-C4 channel: upper 35 (27 – 49), lower 13 (10 – 19), BW 29 (21 – 34)) and sleep. During sleep, episodes with high amplitudes (upper 99 (71 – 125), lower 35 (25 – 44), BW 63 (44 – 81)) corresponded to sleep states N2 – N4. These episodes were interrupted by low amplitudes that were the dominating background pattern towards the morning (upper 39 (30 – 51), lower 16 (11 – 20), BW 23 (19 – 31), sleep states REM, N1, and N2). With increasing age, amplitudes and bandwidths declined. The sensitivity analysis yielded no differences in amplitude values or bandwidths.

Conclusion

aEEG amplitudes and bandwidths were low during wakefulness and light sleep and high during deep sleep in stable children undergoing 24 hour EEG recordings. aEEG values were not altered by antiepileptic drugs in this study.
Gender differences in housework and childcare among Japanese workers during the COVID-19 pandemic
Authors: Sakuragi Toshihide , Tanaka Rie , Tsuji Mayumi , Tateishi Seiichiro , Hino Ayako , Ogami Akira , Nagata Masako , Matsuda Shinya , Fujino Yoshihisa ,   CORoNaWork Project
Published: July 2021

Objectives

Although gender stereotypes regarding paid work and unpaid work are changing, most wives are responsible for taking care of the family and home in Japan. It is unclear how time spent on housework and childcare has changed between working men and women during the COVID-19 pandemic in Japan. The purpose of this study is to investigate how working men and women’s responsibilities for housework and childcare changed during the COVID-19 pandemic in Japan depending on occupation, job type, and the number of employees in the workplace.

Methods

A cross-sectional analysis (N=14,454) was conducted using data from an internet monitoring study (CORoNa Work Project), which was conducted in December 2020. A multilevel logistic model with nested prefectures of residence was conducted to estimate the odds ratio (OR) for change in time devoted to housework and childcare among men and women adjusting for age, household income, frequency of telecommuting, presence of spouse who work, occupation, job type, the number of employees in the workplace, and the incidence rate of COVID-19 by prefecture.

Results

Regardless of occupation related factors, more women than men reported increased time spent on housework and childcare. Furthermore, women were significantly more likely to experience an increase in time spent on those activities than men (housework: OR 1.97, 95% CI [1.75, 2.21], p < 0.001; childcare: OR 1.66, 95% CI [1.37, 2.02], p < 0.001).

Conclusions

The time spent by women on housework and childcare increased significantly compared to men during the COVID-19 pandemic in Japan.
Perceptions of gender equity and markers of achievement in a National Institute for Health Research (NIHR) Biomedical Research Centre (BRC): A qualitative study
Authors: Henderson Lorna R , Dam Rinita , Sarwar Shah Syed Ghulam , Ovseiko Pavel V , Kiparoglou Vasiliki
Published: July 2021

Background

The need to improve gender equity (GE) in academic medicine is well documented. Biomedical Research Centres (BRCs), partnerships between leading National Health Service (NHS) organisations and universities in England, conduct world-class translational research funded by the National Institute for Health Research (NIHR). In 2011, eligibility for BRC funding was restricted to universities demonstrating sustained GE success recognised by the Athena SWAN Charter for Women in Science Silver awards. Despite this structural change, GE research in BRC settings is underdeveloped, yet critical to the acceleration of women’s advancement and leadership.

Objectives

To explore both women’s and men’s perceptions of GE and current markers of achievement in a BRC setting.

Methods

Thematic analysis of data from two discrete research projects: 53 GE survey respondents’ free text comments (34 women, 16 men), and 16 semi structured interviews with women affiliated to the NIHR Oxford BRC.

Results

Four major themes emerged from the analysis: perceptions of the Athena Swan Charter for Women in Science (GE policy); views on monitoring GE in BRCs; views on current markers of achievement in academia and GE; and recommendations for actions to improve GE in BRC settings. Monitoring of GE in BRCs was deemed to be important, but complex. Participants felt current markers of achievement were not equitable to women as they did not take contextual factors into account such as maternity leave and caring responsibilities. BRC specific organisational policies and metrics are required to monitor and catalyse GE.

Conclusions

Markers of achievement for monitoring GE in BRCs should take into account contextual factors specific to BRCs and women’s career progression and professional advancement. GE markers of achievement should be complimented with broader aspects of equality, diversity and inclusion.
COVID-ONE-humoral immune: The One-stop Database for COVID-19-specific Antibody Responses and Clinical Parameters
Authors: Xu Zhaowei , Li Yang , Lei Qing , Huang Likun , Lai Dan-yun , Guo Shu-juan , Jiang He-wei , Hou Hongyan , Zheng Yun-xiao , Wang Xue-ning , Wu Jiaoxiang , Ma Ming-liang , Zhang Bo , Chen Hong , Yu Caizheng , Xue Jun-biao , Zhang Hai-nan , Qi Huan , Yu Siqi , Lin Mingxi , Zhang Yandi , Lin Xiaosong , Yao Zongjie , Sheng Huiming , Sun Ziyong , Wang Feng , Fan Xionglin , Tao Sheng-ce
Published: July 2021

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (COVID-ONE humoral immune). COVID-ONE humoral immunity is based on a dataset that contains the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 COVID-19 samples collected from 783 patients. In addition, 96 clinical parameters for the 2,360 samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE humoral immune provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the “START” button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-humoral immune is freely available at www.COVID-ONE.cn.
Structural basis for the therapeutic advantage of dual and triple agonists at the human GIP, GLP-1 or GCG receptors
Authors: Zhao Fenghui , Zhou Qingtong , Cong Zhaotong , Hang Kaini , Zou Xinyu , Zhang Chao , Chen Yan , Dai Antao , Liang Anyi , Ming Qianqian , Wang Mu , Chen Linan , Xu Peiyu , Chang Rulue , Feng Wenbo , Xia Tian , Zhang Yan , Wu Beili , Yang Dehua , Zhao Lihua , Xu H. Eric , Wang Ming-Wei
Published: July 2021

Glucose homeostasis, regulated by glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) is critical to human health. Several multi-targeting agonists at GIPR, GLP-1R or GCGR, developed to maximize metabolic benefits with reduced side-effects, are in clinical trials to treat type 2 diabetes and obesity. To elucidate the molecular mechanisms by which tirzepatide, a GIPR/GLP-1R dualagonist, and peptide 20, a GIPR/GLP-1R/GCGR triagonist, manifest their superior efficacies over monoagonist such as semaglutide, we determined cryo-electron microscopy structures of tirzepatide-bound GIPR and GLP-1R as well as peptide 20-bound GIPR, GLP-1R and GCGR The structures reveal both common and unique features for the dual and triple agonism by illustrating key interactions of clinical relevance at the atomic level. Retention of glucagon function is required to achieve such an advantage over GLP-1 monotherapy. Our findings provide valuable insights into the structural basis of functional versatility and therapeutic supremacy of tirzepatide and peptide 20.
Identification of an isoflavonoid transporter required for the nodule establishment of the Rhizobium-Fabaceae symbiotic interaction
Authors: Biała-Leonhard Wanda , Zanin Laura , Gottardi Stefano , de Brito Francisco Rita , Venuti Silvia , Valentinuzzi Fabio , Mimmo Tanja , Cesco Stefano , Bassin Barbara , Martinoia Enrico , Pinton Roberto , Jasiński Michał , Tomasi Nicola
Published: July 2021

Nitrogen (N) as well as Phosphorus (P) are key nutrients determining crop productivity. Legumes have developed strategies to overcome nutrient limitation by e.g., forming a symbiotic relationship with N-fixing rhizobia and the release of P-mobilizing exudates and are thus able to grow without supply of N or P fertilizers. The legume-rhizobial symbiosis starts with root release of isoflavonoids, that act as signaling molecules perceived by compatible bacteria. Subsequently, bacteria release nod factors, which induce signaling cascades allowing the formation of functional N-fixing nodules.

We report here the identification and functional characterization of a plasma membrane-localized MATE-type transporter (LaMATE2) involved in the release of genistein from white lupin roots.

The LaMATE2 expression in the root is upregulated under N deficiency as well as low phosphate availability, two nutritional deficiencies that induce the release of this isoflavonoid. LaMATE2 silencing reduced genistein efflux and even more the formation of symbiotic nodules, supporting the crucial role of LaMATE2 in isoflavonoid release and nodulation. Furthermore, silencing of LaMATE2 limited the P-solubilization activity of lupin root exudates. Transport assays in yeast vesicles demonstrated that LaMATE2 acts as a proton-driven isoflavonoid transporter.
A method for the generation of pseudotyped virus particles bearing SARS coronavirus spike protein in high yields
Authors: Fujioka Yoichiro , Kashiwagi Sayaka , Yoshida Aiko , Satoh Aya O. , Fujioka Mari , Amano Maho , Yamauchi Yohei , Ohba Yusuke
Published: July 2021

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has threatened human health and the global economy. Development of additional vaccines and therapeutics is urgently required, but such development with live virus must be conducted with biosafety level 3 confinement. Pseudotyped viruses have been widely adopted for studies of virus entry and pharmaceutical development to overcome this restriction. Here we describe a modified protocol to generate vesicular stomatitis virus (VSV) pseudotyped with SARS-CoV or SARS-CoV-2 Spike protein in high yield. We found that pseudovirions produced with the conventional transient expression system lacked coronavirus Spike protein at their surface as a result of inhibition of parental VSV infection by overexpression of this protein. Establishment of stable cell lines with an optimal expression level of coronavirus Spike protein allowed the efficient production of progeny pseudoviruses decorated with Spike protein. This improved VSV pseudovirus production method should facilitate studies of coronavirus entry and development of antiviral agents.