bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrity of the Post-LRR Domain Is Required for TIR-NB-LRR Function
Authors: Saucet Simon B. , Esmenjaud Daniel , Van Ghelder Cyril
Published: November 2020

Plants trigger appropriate defense responses, notably, through intracellular nucleotide-binding (NB) and leucine-rich repeat (LRR)-containing receptors (NLRs) that detect secreted pathogen effector proteins. In NLR resistance genes, the toll/interleukin-1 receptor (TIR)-NB-LRR proteins (TNLs) are an important subfamily, out of which approximately half the members carry a post-LRR (PL) domain of unknown role. We first investigated the requirement of the PL domain for TNL-mediated immune response by mutating the most conserved amino acids across PL domains of Arabidopsis thaliana TNLs. We identified several amino acids in the PL domain of RPS4, required for its ability to trigger a hypersensitive response to AvrRps4 in a Nicotiana tabacum transient assay. Mutating the corresponding amino acids within the PL domain of the tobacco TNL gene N also affected its function. Consequently, our results indicate that the integrity of the PL domain at conserved positions is crucial for at least two unrelated TNLs. We then tested the PL domain specificity for function by swapping PL domains between the paralogs RPS4 and RPS4B. Our results suggest that the PL domain is involved in their TNL pair specificity, ‘off state’ stability, and NLR complex activation. Considering genetically paired Arabidopsis TNLs, we finally compared the PL and TIR domains of their sensor and executor sequences, respectively. While TIR and PL domains from executors present complete motifs, sensors showed a lack of conservation with degenerated motifs. We here provide a contribution to the functional analysis of the PL domain in order to decipher its role for TNL function.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Factors Associated With Non-enrollment of Center-Based Cardiovascular Rehabilitation Program Among Transient Ischemic Attack or Mild Stroke Patients
Authors: Meng Guangxia , Qazi Hammad , Chen Helen
Published: November 2020

Purpose:

Cardiovascular rehabilitation programs (CRPs) are effective in secondary stroke prevention, yet the enrollment rate is suboptimal. This study aims to identify demographic and clinical factors and patient-reported reasons for non-enrollment in a center-based outpatient CRP among patients with transient ischemic attack (TIA) or mild stroke.

Methods:

This mixed-method retrospective chart review was conducted in an outpatient CRP affiliated with a tertiary care hospital in Canada from January 2009 to October 2017. A total of 621 patients with TIA or mild stroke were included. Multiple logistic regression was used to determine the relationship between demographic and clinical predictors with non-enrollment. A thematic analysis of multidisciplinary progress notes was done for the non-enrollment subgroup of patients to understand the patient-reported reasons.

Results:

The non-enrollment rate was 42%. Travel distance to CRP (OR = 1.024; 95% CI, 1.010-1.038), age (OR = 1.023; 95% CI, 1.004-1.042), and current smoking status (OR = 1.935; 95% CI, 1.230-3.042) were associated with non-enrollment. The patient-reported reasons for non-enrollment were occurrence of new medical events and comorbidities, their perceptions of health and CRP, transportation, work/time conflict, and distance.

Conclusions:

This study found that patients with TIA or mild stroke who were older, lived farther from the CRP center, or were current smokers were less likely to enroll in a CRP. The present findings may help clinicians identify patients unlikely to enroll in a CRP and allow the implementation of interventions focused on health education and physical activity to improve enrollment. Future research should validate these factors in multiple settings using prospective mixed methods so that interventions can be developed to address non-enrollment in the CRP.
Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity
Authors: Mishra Anusha , Hall Catherine N. , Howarth Clare , Freeman Ralph D.
Published: November 2020

Functional neuroimaging using MRI relies on measurements of blood oxygen level-dependent (BOLD) signals from which inferences are made about the underlying neuronal activity. This is possible because neuronal activity elicits increases in blood flow via neurovascular coupling, which gives rise to the BOLD signal. Hence, an accurate interpretation of what BOLD signals mean in terms of neural activity depends on a full understanding of the mechanisms that underlie the measured signal, including neurovascular and neurometabolic coupling, the contribution of different cell types to local signalling, and regional differences in these mechanisms. Furthermore, the contributions of systemic functions to cerebral blood flow may vary with ageing, disease and arousal states, with regard to both neuronal and vascular function. In addition, recent developments in non-invasive imaging technology, such as high-field fMRI, and comparative inter-species analysis, allow connections between non-invasive data and mechanistic knowledge gained from invasive cellular-level studies. Considered together, these factors have immense potential to improve BOLD signal interpretation and bring us closer to the ultimate purpose of decoding the mechanisms of human cognition. This theme issue covers a range of recent advances in these topics, providing a multidisciplinary scientific and technical framework for future work in the neurovascular and cognitive sciences.

This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity'.
The thermodynamics of thinking: connections between neural activity, energy metabolism and blood flow
Authors: Buxton Richard B.
Published: November 2020

Several current functional neuroimaging methods are sensitive to cerebral metabolism and cerebral blood flow (CBF) rather than the underlying neural activity itself. Empirically, the connections between metabolism, flow and neural activity are complex and somewhat counterintuitive: CBF and glycolysis increase more than seems to be needed to provide oxygen and pyruvate for oxidative metabolism, and the oxygen extraction fraction is relatively low in the brain anddecreaseswhen oxygen metabolism increases. This work lays a foundation for the idea that this unexpected pattern of physiological changes is consistent with basic thermodynamic considerations related to metabolism. In the context of this thermodynamic framework, the apparent mismatches in metabolic rates and CBF are related to preserving the entropy change of oxidative metabolism, specifically the O2/CO2ratio in the mitochondria. However, the mechanism supporting this CBF response is likely not owing to feedback from a hypothetical O2sensor in tissue, but rather is consistent with feed-forward control by signals from both excitatory and inhibitory neural activity. Quantitative predictions of the thermodynamic framework, based on models of O2and CO2transport and possible neural drivers of CBF control, are in good agreement with a wide range of experimental data, including responses to neural activation, hypercapnia, hypoxia and high-altitude acclimatization.

This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.
Cross-species neuroscience: closing the explanatory gap
Authors: Barron Helen C. , Mars Rogier B. , Dupret David , Lerch Jason P. , Sampaio-Baptista Cassandra
Published: November 2020

Neuroscience has seen substantial development in non-invasive methods available for investigating the living human brain. However, these tools are limited to coarse macroscopic measures of neural activity that aggregate the diverse responses of thousands of cells. To access neural activity at the cellular and circuit level, researchers instead rely on invasive recordings in animals. Recent advances in invasive methods now permit large-scale recording and circuit-level manipulations with exquisite spatio-temporal precision. Yet, there has been limited progress in relating these microcircuit measures to complex cognition and behaviour observed in humans. Contemporary neuroscience thus faces an explanatory gap between macroscopic descriptions of the human brain and microscopic descriptions in animal models. To close the explanatory gap, we propose adopting a cross-species approach. Despite dramatic differences in the size of mammalian brains, this approach is broadly justified by preserved homology. Here, we outline a three-armed approach for effective cross-species investigation that highlights the need to translate different measures of neural activity into a common space. We discuss how a cross-species approach has the potential to transform basic neuroscience while also benefiting neuropsychiatric drug development where clinical translation has, to date, seen minimal success.

This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.
Regional variation in neurovascular coupling and why we still lack a Rosetta Stone
Authors: Ekstrom Arne D.
Published: November 2020

Functional magnetic resonance imaging (fMRI) is the dominant tool in cognitive neuroscience although its relation to underlying neural activity, particularly in the human brain, remains largely unknown. A major research goal, therefore, has been to uncover a ‘Rosetta Stone’ providing direct translation between the blood oxygen level-dependent (BOLD) signal, the local field potential and single-neuron activity. Here, I evaluate the proposal that BOLD signal changes equate to changes in gamma-band activity, which in turn may partially relate to the spiking activity of neurons. While there is some support for this idea in sensory cortices, findings in deeper brain structures like the hippocampus instead suggest both regional and frequency-wise differences. Relatedly, I consider four important factors in linking fMRI to neural activity: interpretation of correlations between these signals, regional variability in local vasculature, distributed neural coding schemes and varying fMRI signal quality. Novel analytic fMRI techniques, such as multivariate pattern analysis (MVPA), employ the distributed patterns of voxels across a brain region to make inferences about information content rather than whether a small number of voxels go up or down relative to baseline in response to a stimulus. Although unlikely to provide a Rosetta Stone, MVPA, therefore, may represent one possible means forward for better linking BOLD signal changes to the information coded by underlying neural activity.

This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.
Forging a path to mesoscopic imaging success with ultra-high field functional magnetic resonance imaging
Authors: Weldon Kimberly B. , Olman Cheryl A.
Published: November 2020

Functional magnetic resonance imaging (fMRI) studies with ultra-high field (UHF, 7+ Tesla) technology enable the acquisition of high-resolution images. In this work, we discuss recent achievements in UHF fMRI at the mesoscopic scale, on the order of cortical columns and layers, and examine approaches to addressing common challenges. As researchers push to smaller and smaller voxel sizes, acquisition and analysis decisions have greater potential to degrade spatial accuracy, and UHF fMRI data must be carefully interpreted. We consider the impact of acquisition decisions on the spatial specificity of the MR signal with a representative dataset with 0.8 mm isotropic resolution. We illustrate the trade-offs in contrast with noise ratio and spatial specificity of different acquisition techniques and show that acquisition blurring can increase the effective voxel size by as much as 50% in some dimensions. We further describe how different sources of degradations to spatial resolution in functional data may be characterized. Finally, we emphasize that progress in UHF fMRI depends not only on scientific discovery and technical advancement, but also on informal discussions and documentation of challenges researchers face and overcome in pursuit of their goals.

This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.
Acinetobacter lanii sp. nov., Acinetobacter shaoyimingii sp. nov. and Acinetobacter wanghuae sp. nov., isolated from faeces of Equus kiang
Authors: Zhu Wentao , Dong Kui , Yang Jing , Lu Shan , Lai Xin-He , Pu Ji , Jin Dong , Huang Yuyuan , Zhang Sihui , Zhou Juan , Huang Ying , Xu Jianguo
Published: November 2020

Six aerobic, non-motile, non-haemolytic, Gram-stain-negative, oxidase-negative strains (185T, 187, 323-1T, 194, dk386T and dk771) were recovered from different faecal samples of Equus kiang on the Qinghai–Tibet Plateau. In the 16S rRNA gene sequences, one strain pair, 185T/187, shared highest similarity to

Acinetobacter equi

114T (97.9 %), and the other two (323-1T/194 and dk771T/dk386) to

Acinetobacter harbinensis

CGMCC 1.12528T (98.6 and 97.0 %, respectively). Phylogenomic tree analysis showed that these six strains formed three separate clades in the genus

Acinetobacter

. Digital DNA–DNA hybridization values of each pair of the isolates with all members of the genus

Acinetobacter

were far below 70 %. The main cellular fatty acids of all six strains were C18 : 1
 ω9c, C16 : 0 and summed feature 3 (C16 : 1
 ω7c/C16 : 1
 ω6c). Q-9 was the predominant respiratory quinone for strains 185T, 323-1T and dk386T. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. Based on the genotypic, phenotypic and biochemical analyses, these six strains represent three novel species of the genus

Acinetobacter

, for which the names Acinetobacter lanii sp. nov., Acinetobacter shaoyimingii sp. nov. and Acinetobacter wanghuae sp. nov. are proposed. The type strains are 185T (=CGMCC 1.13636T=JCM 33607T), 323-1T (=CGMCC 1.13940T=JCM 33608T) and dk386T (=CGMCC 1.16589T=JCM 33592T), respectively.
Mutations in TP53 and other heterogeneous genes help to distinguish metastases from new primary malignancies
Authors: Prall Owen W. J. , Vedururu Ravikiran , Lau Peter , Fellowes Andrew
Published: November 2020

Background

Distinguishing metastases from new primary malignancies or vice versa is important because misclassification can result in inappropriate management. However, for some cases this distinction can be challenging, particularly for squamous cell carcinomas in which the usual surgical pathology approach, predominantly morphology and immunohistochemistry, are frequently non-contributory. We analysed tumor-associated mutations in order to determine whether they could help with this diagnostic dilemma.

Methods

Mutations in specific genes were identified with cBioPortal, a large publically available tumor sequence data set. Genes were selected based upon either their high overall prevalence of mutation, or their inclusion in an in-house tumor sequencing set. Tumor types analysed included various common adenocarcinomas, squamous cell carcinomas from multiple sites, urothelial carcinoma and melanoma. Individual mutations and sets of mutations within gene cohorts were compared by their diversity (or heterogeneity) index, prevalence and cumulative prevalence. We demonstrated the utility of this method by performing in-house sequencing of candidate genes in tumors from three patients for which morphology and immunohistochemistry were unable to distinguish between a metastasis and a new primary malignancy.

Results

Sequence data from relatively small cohorts of candidate genes readily identified highly diverse, low prevalence mutation profiles in most common malignancies including squamous cell carcinomas. The diversity index predicted the likelihood of an identical mutation profile occurring in an unrelated tumor. High yield gene cohorts could be predicted based on the primary tumor type. Most cohorts included TP53 due to both its high mutation prevalence and high mutation index of diversity. Identical, low prevalence mutations in multiple tumors from patients in the three case studies provided strong diagnostic certainty for metastases rather than new primary malignancies.

Conclusions

Most common tumors, including squamous cell carcinomas, have a readily identifiable mutation profiles that occur at a sufficiently low prevalence to effectively barcode or fingerprint the tumor. An identical mutation profile in a primary tumor and a new lesion provides strong evidence for a metastasis and effectively excludes a new primary malignancy, providing diagnostic confidence and aiding clinical management certainty.
A hidden Markov model reliably characterizes ketamine-induced spectral dynamics in macaque LFP and human EEG
Authors: Garwood Indie C. , Chakravarty Sourish , Donoghue Jacob , Kahali Pegah , Chamadia Shubham , Akeju Oluwaseun , Miller Earl K. , Brown Emery N.
Published: November 2020

Ketamine is an NMDA receptor antagonist commonly used to maintain general anesthesia. At anesthetic doses, ketamine causes bursts of 30-50 Hz oscillations alternating with 0.1 to 10 Hz oscillations. These dynamics are readily observed in local field potentials (LFPs) of non-human primates (NHPs) and electroencephalogram (EEG) recordings from human subjects. However, a detailed statistical analysis of these dynamics has not been reported. We characterize ketamine’s neural dynamics using a hidden Markov model (HMM). The HMM observations are sequences of spectral power in 10 Hz frequency bands between 0 to 50 Hz, where power is averaged within each band and scaled between 0 and 1. We model the observations as realizations of multivariate beta probability distributions that depend on a discrete-valued latent state process whose state transitions obey Markov dynamics. Using an expectation-maximization algorithm, we fit this beta-HMM to LFP recordings from 2 NHPs, and separately, to EEG recordings from 9 human subjects who received anesthetic doses of ketamine. Together, the estimated beta-HMM parameters and optimal state trajectory revealed an alternating pattern of states characterized primarily by gamma burst and slow oscillation activity, as well as intermediate states in between. The mean duration of the gamma burst state was 2.5s([1.9,3.4]s) and 1.2s([0.9,1.5]s) for the two NHPs, and 2.7s([1.9,3.8]s) for the human subjects. The mean duration of the slow oscillation state was 1.6s([1.1,2.5]s) and 0.7s([0.6,0.9]s) for the two NHPs, and 2.8s([1.9,4.3]s) for the human subjects. Our beta-HMM framework provides a useful tool for experimental data analysis. Our characterizations of the gamma-burst process offer detailed, quantitative constraints that can inform the development of rhythm-generating neuronal circuit models that give mechanistic insights into this phenomenon and how ketamine produces altered states of arousal.
Oncogene Concatenated Enriched Amplicon Nanopore Sequencing for Rapid, Accurate, and Affordable Somatic Mutation Detection
Authors: Thirunavukarasu Deepak , Cheng Lauren Y. , Song Ping , Chen Sherry X. , Borad Mitesh J. , Kwong Lawrence , James Phillip , Turner Daniel J. , Zhang David Yu
Published: November 2020

Nanopore sequencing is more than 10-fold faster than sequencing-by-synthesis and provides reads that are roughly 100-fold longer. However, nanopore sequencing’s 7.5% intrinsic error rate renders it difficult to call somatic mutations with low variant allele frequencies (VAFs) without significant false positives. Here, we introduce the Oncogene Concatenated Enriched Amplicon Nanopore Sequencing (OCEANS) method, in which variants with low VAFs are selectively amplified and subsequently concatenated for nanopore sequencing. OCEANS allows accurate detection of somatic mutations with VAF limits of detection between 0.05% and ≤ 1%. We constructed 4 distinct multi-gene OCEANS panels targeting recurrent mutations in acute myeloid leukemia, melanoma, non-small-cell lung cancer, and hepatocellular carcinoma. Comparison experiments against Illumina NGS showed 99.79% to 99.99% area under the receiver-operator curve for these panels on clinical FFPE tumor samples. Furthermore, we identified a significant number of mutations below the standard NGS limit of detection in clinical tissue samples using each OCEANS panel. Comparison against digital PCR on 10 of putative mutations at ≤1% VAF showed 9 concordant positive calls with VAFs between 0.02% and 0.66%. By overcoming the primary challenge of nanopore sequencing on detecting low VAF single nucleotide variant mutations, OCEANS is poised to enable same-day clinical sequencing panels.
Assessing the magnitude of and factors associated to demand for long acting reversible and permanent contraceptive methods among sexually active women in Kenya
Authors: Waithaka Michael W. , Gichangi Peter , Thiongo Mary
Published: November 2020

Introduction

Though there has been an increase in use of long acting and permanent methods of contraception (LAPMs) globally over the last decade, the rates of unintended pregnancy still remain high. In Sub-Saharan African and especially in Kenya, while there has been increase in the uptake of LAPMs over the past years, there are limited recently available evidences on the real magnitude, recent trends and factors associated to demand for LAPMs among sexually active women in the reproductive age.

Methods

In this study, we used data from seven survey rounds (2014 to 2018) of a nationally representative Performance Monitoring and Accountability 2020 (PMA2020) household and female survey. PMA2020 survey is based on a multi-stage cluster sample design to draw a probability sample of households and eligible females. In this analysis, both descriptive and inferential statistics were used for data analysis and interpretations. Statistical significance was considered for p-values <0.05. STATA 16.0 software was used for all analyses.

Results

Among the 17,455 sexually active women in the reproductive age included in this study, 83.1% had demand for LAPMs. The total demand for LAPMs significantly decreased from 85.0% in 2014 to 81.0% in 2018. Age of the respondents, marital status, parity, rural/urban residence, county of residence and access to Family Planning/contraceptives information via media in the last 12 months were significantly associated with demand for LAPMs.

Conclusion

The total demand for LAPMs among sexually active women in Kenya is high, with the bigger share of the demand being unmet. Targeted programs to satisfy the existing demand of LAPMs and address the issue of unmet need for LAPMs should be put in place to ensure no woman is left behind. Similarly, programmers/advocates should utilize the locally available channels e.g. the media to generate new demand and overturn the decreasing demand for LAPMs.

STRENGTHS AND LIMITATIONS OF THIS STUDY

The nationally representative Performance Monitoring and Accountability 2020 (PMA2020) surveys are modelled on the insight from Demographic and Health Survey (DHS).

PMA2020 uses standardized questionnaires (with questions extracted from DHS which have been validated and are extensively used in FP programs) to gather data about households and individual females that are comparable across program countries and consistent with existing national surveys.

There are strengths to the PMA2020 survey which include inclusion of a large sample of women, use of data collectors without medical training and real-time data collection with sufficient controls for quality assurance.

There are some limitations to consider when interpreting the data. Some outputs of this study utilized pooled data from seven-rounds of PMA2020 survey.
Associations between solid fuel use and early child development among 3 to 4 years old children in Bangladesh: Evidence from a nationally representative survey
Authors: Rana Juwel , Gutierrez Patricia Luna , Haque Syed Emdadul , Nazif-Muñoz José Ignacio , Mitra Dipak K. , Oulhote Youssef
Published: November 2020

Background

Household Air Pollution (HAP) from solid fuel use (SFU) may have impacts on children’s health in low-resources countries. Despite these potential health effects, SFU is still highly prevalent in Bangladesh.

Objectives

This study was conducted to assess the associations between SFU and early childhood development index (ECDI) among under-five children in Bangladesh and explore the potential effect modification by sex and urbanicity.

Materials and methods

This cross-sectional study used Bangladesh Multiple Indicator Cluster Survey (MICS) 2019, a nationally representative survey data collected by UNICEF from all 64 districts in Bangladesh. The ECDI consisted of ten different items across four developmental domains: literacy-numeracy, physical, social-emotional development, and learning skills in the early years of life (36 to 59 months). A total of 9,395 children aged 36 to 59 months were included in this analysis. We used multilevel Poisson regression models with a robust variance where SFU was a proxy indicator for HAP exposure.

Results

Children exposed to SFU were 1.47 times more likely to be not developmentally on track (95% CI: 1.25, 1.73; <0.001)compared to children with no SFU exposure. Two sub-domains explained these associations, SFU was significantly associated with socio-emotional development (prevalence ratio [PR]: 1.17; 95% CI: 1.01, 1.36; p=0.035), and learning-cognitive development (PR: 1.90; 95% CI: 1.39, 2.60; p<0.001). Associations between SFU and ECDI were not significantly different (p-difference=0.210) between girls (PR: 1.64; 95% CI: 1.31, 2.07) and boys (PR: 1.37; 95% CI: 1.13, 1.65). Likewise, urbanicity did not modify the associations between SFU and ECDI outcomes.

Conclusion

Bangladeshi children aged 36-59 months exposed to SFU exhibited delays in childhood development compared to unexposed children. Public health policies should promote a better early life environment for younger children to meet their developmental milestones by reducing the high burden of HAP exposure in low-resource settings where most disadvantaged kids struggle to reach their full developmental potentials.
Social Isolation among Mothers Caring for Infants in Japan: Findings from the Nationwide Survey of Healthy Parents and Children 21
Authors: Yamazaki Sayaka , Akiyama Yuka , Shinohara Ryoji , Yamagata Zentaro
Published: November 2020

Background

Child-rearing isolation may increase the risk of child abuse and negatively affect child development owing to increased urbanization and decline in family and community support systems.

Purpose

This study aimed to identify the prevalence of child-rearing isolation and the related sociodemographic factors among mothers in Japan using data from the Final Survey of Healthy Parents and Children 21.

Participants

Mothers of young children attending their health checkups.

Methods

Multivariate logistic regression models assessed the association between child-rearing isolation and socio-demographic variables. Data from 69,337 women were analyzed.

Results

Mothers who experienced child-rearing isolation comprised 0.2% of all participants. Mothers who were 35- to 39-years-old at childbirth (OR = 1.6, CI[1.0, 2.4], p = .036), unemployed (OR = 1.7, CI[1.3, 2.4], p = .001), experienced financial difficulty (OR = 1.8, CI[1.3, 2.5], p < .001), had husbands with limited participation in child-rearing (OR = 5.7, CI[4.2, 7.9], p < .001), lived in special wards in Tokyo Metropolis (OR = 4.2, CI[2.2, 8.3], p < .001), had child abuse concerns (OR = 2.1, CI [1.5, 2.9], p < .001), and had no time to relax with their child (OR = 4.5, CI [3.1-6.7], p < .001) exhibited higher odds ratio for child-rearing isolation, compared to those who did not.

Conclusions

Findings showed the impact of urban living on maternal health, the influence of isolation on mothers’ anxiety about child-rearing and their potential for child maltreatment. The importance of fathers’ involvement in child-rearing for preventing maternal child-rearing isolation was highlighted.

Significance

Previous studies have shown that social isolation is significantly associated with morbidity and mortality. One of the most pressing issues in Japan is child-rearing isolation of mothers with infants. Child-rearing isolation is considered a risk factor for abuse and disruption of healthy parent-child relationships. However, no studies have examined the associated factors of child-rearing isolation among mothers, adjusting for confounding factors. Our results provide evidence that child-rearing isolation is a risk factor for maltreatment. In addition, we found new evidence that maternal child-rearing isolation is significantly associated with age at birth, lack of spousal participation in parenting, and urban living.
Association between climate and new daily diagnoses of COVID-19
Authors: Mattiuzzi Camilla , Henry Brandon M. , Sanchis-Gomar Fabian , Lippi Giuseppe
Published: November 2020

Background

Although evidence is accumulating that climate conditions may positively or negatively influence the scale of coronavirus disease 2019 (COVID-19) outbreaks, uncertainty remains concerning the real impact of climate factors on viral transmission. Methods. The number of new daily cases of COVID-19 diagnosed in Verona (Italy) was retrieved from the official website of Veneto Region, while information on daily weather parameters in the same area was downloaded from IlMeteo website, a renowned Italian technological company specialized in weather forecasts. The search period ranged between March 1 to November 11, 2020. The number of new daily COVID-19 cases and meteorological data in Verona were correlated using both univariate and multivariate analysis.

Results

The number of daily COVID-19 diagnoses in Verona was positively associated with the number of days in lockdown and humidity, and inversely correlated with mean, min and max temperature, mean wind speed and number of days with rainfall. Days of lockdown, mean air temperature, humidity, mean wind speed and number of days with rainfall remained significantly associated in multivariate analysis. The four weather parameters contributed to explaining 61% of variance in new daily COVID-19 diagnoses. Each 1% increase in air temperature, 1% decrease in humidity, 1 km/h increase in wind speed and day with rainfall were independently associated with 1.0%, 0.3%, 1.2% and 5.4% reduction in new COVID-19 daily diagnoses. A significant difference was observed in values of all-weather parameters recorded in Verona between days with <100 or ≥100 new daily COVID-19diagnoses.

Conclusions

Climate conditions may play an essential role in conditions of viral transmission, and influence the likelihood or course of local outbreaks. Preventive measures, testing policies and hospital preparedness should be reinforced during periods of higher meteorological risk and in local environments with adverse climate conditions.
Moving in on human motor cortex. Characterizing the relationship between body parts with non-rigid population Response Fields
Authors: Schellekens Wouter , Bakker Carlijn , Ramsey Nick F. , Petridou Natalia
Published: November 2020

For cortical motor activity, the relationships between different body part representations is unknown. Through reciprocal body part relationships, functionality of cortical motor areas with respect to whole body motor control can be characterized. In the current study, we investigate the relationship between body part representations within individual neuronal populations in motor cortices, following a 7 Tesla fMRI 18-body-part motor experiment in combination with our newly developed non-rigid population Response Field (pRF) model and graph theory. The non-rigid pRF metrics reveal somatotopic structures in all included motor cortices covering frontal, parietal, medial and insular cortices and that neuronal populations in primary sensorimotor cortex respond to fewer body parts than secondary motor cortices. Reciprocal body part relationships are estimated in terms of uniqueness, clique-formation, and importance. We report unique response profiles for the knee, a clique of body parts surrounding the ring finger, and a central role for the shoulder and wrist. These results reveal associations among body parts from the perspective of the central nervous system, while being in agreement with intuitive notions of body part usage.
A Digital Survey on the Acceptance and Affordability of COVID 19 Vaccine among the People of West Bengal, India- A Survey Based Study
Authors: Gautam Arunodaya , Dhara Bikram , Mukherjee Dattatreya , Mukhopadhyay Debraj , Roy Sayan , Ganguly Soumya Sarathi , Chowdhury Ankita Dutta , Goswami Shubham , Dey Swapnil , Basu Srishti , Banerjee Deboshmita , Chatterjee Soumi , Roy Ishita , Mitra Arup Kumar
Published: November 2020

Overview

Currently, multiple vaccines for coronavirus disease 2019 (COVID-19) are in clinical trials. In Oct-Nov 2020, 1078 individuals in West Bengal surveyed to evaluate possible acceptance rates, affordability and factors affecting the acceptance of a vaccine for COVID-19.

Result

77.27 percent of respondents reported that they would be very or very likely to take a vaccine for COVID-19, 5.3 percent don’t want to take vaccine and 12.24 don’t know about their decision. In that 58 percent respondents want to take Indian Vaccine; 19 percent respondents want to take foreign vaccine. Other respondents can take any vaccine. The affordability, 40 percent respondents want a vaccine bellow 500 INR, 25 percent respondents want a vaccine of 500-1000 INR. 11 percent respondents want vaccine of over 1000 INR.

Method of Study

The google form is prepared with the questions on acceptance and affordability of vaccines. The form is circulated digitally among the people and then we have collected the data in excel. Based on the result we have prepared our statistical graphs.

Conclusion

Majority of Responders want a COVID 19 vaccine. Majority responders want Indian COVID19 Vaccine. Majority responders want a vaccine in a cost of below 500 INR.
Epigenetic clocks are not accelerated in COVID-19 patients
Authors: Franzen Julia , Nüchtern Selina , Tharmapalan Vithurithra , Vieri Margherita , Nikolić Miloš , Han Yang , Balfanz Paul , Marx Nikolaus , Dreher Michael , Brümmendorf Tim H. , Dahl Edgar , Beier Fabian , Wagner Wolfgang
Published: November 2020

Age is a major risk factor for severe outcome of coronavirus disease 2019 (COVID-19), but it remains unclear if this is rather due to increased chronological age or biological age. During lifetime, specific DNA methylation changes are acquired in our genome that act as “epigenetic clocks” allowing to estimate donor age and to provide a surrogate marker for biological age. In this study, we followed the hypothesis that particularly patients with accelerated epigenetic age are affected by severe outcomes of COVID-19. Using four different age predictors, we did not observe accelerated age in global DNA methylation profiles of blood samples of nine COVID-19 patients. Alternatively, we used targeted bisulfite amplicon sequencing of three age-associated genomic regions to estimate donor-age of blood samples of 95 controls and seventeen COVID-19 patients. The predictions correlated well with chronological age, while COVID-19 patients even tended to be predicted younger than expected. Furthermore, lymphocytes in nineteen COVID-19 patients did not reveal significantly accelerated telomere attrition. Our results demonstrate that these biomarkers of biological age are therefore not suitable to predict a higher risk for severe COVID-19 infection in elderly patients.
Development of the Aerial Remote Triage System: Result of a survey of international experts
Authors: Álvarez-García Cristina , Cámara-Anguita Sixto , López-Hens José María , Granero-Moya Nani , López-Franco María Dolores , María-Comino-Sanz Inés , Sanz-Martos Sebastián , Pancorbo-Hidalgo Pedro Luis
Published: November 2020

The use of drones for the triage of victims in mass-casualty incidents has recently emerged as a promising technology. However, there is not a triage system really adapted to a remote usage. The objective of our study was to develop a remote triage procedure using drones. The research was performed in three stages: literature review, development of a remote triage algorithm using drones and evaluation of the algorithm by experts. A qualitative synthesis and the calculation of content validity ratios were done to achieve the Aerial Remote Triage System. The system assesses first major bleeding, second walking, third conscious (awake) and fourth sign of life; and classify the victims inside priority categories: priority 1 (red), priority 2 (yellow), priority 3 (green) and priority * (violet). It includes the possibility to indicate save-living interventions to victims and bystanders, like the compression of bleeding injuries or the recovery position. The Aerial Remote Triage System is valid in complex health emergencies when it is difficult or impossible an immediate access to the scene due to physical, chemical or biological risks. It can be useful to know vital information about the emergencies.
Assessment of the Impacts of Pharmaceutical and Non-pharmaceutical Intervention on COVID-19 in South Africa Using Mathematical Model
Authors: Musa Rabiu , Ezugwu Absalom E. , Mbah Godwin C. E.
Published: November 2020

The novel coronal virus has spread across more than 213 countries within the space of six months causing devastating public health hazard and monumental economic loss. In the absence of clinically approved pharmaceutical intervention, attentions are shifted to non-pharmaceutical controls to mitigate the burden of the novel pandemic. In this regard, a ten mutually exclusive compartmental mathematical model is developed to investigate possible effects of both pharmaceutical and non-pharmaceutical controls incorporating both private and government’s quarantine and treatments. Several reproduction numbers were calculated and used to determine the impact of both control measures as well as projected benefits of social distancing, treatments and vaccination. We investigate and compare the possible impact of social distancing incorporating different levels of vaccination, with vaccination programme incorporating different levels of treatment. Using the officially published South African COVID-19 data, the numerical simulation shows that the community reproduction threshold will be 30 when there is no social distancing but will drastically reduced to 5 (about 83% reduction) when social distancing is enforced. Furthermore, when there is vaccination with perfect efficacy, the community reproduction threshold will be 4 which increases to 12 (about 67% increment) with-out vaccination. We also established that the implementation of both interventions is enough to curtail the spread of COVID-19 pandemic in South Africa which is in confirmation with the recommendation of the world health organization.
Evaluation of the Panbio™ rapid antigen test for SARS-CoV-2 in primary health care centers and test sites
Authors: Bulilete Oana , Lorente Patricia , Leiva Alfonso , Carandell Eugenia , Oliver Antonio , Rojo Estrella , Pericas Pau , Llobera Joan
Published: November 2020

Background

Rapid antigen tests (Ag-RDT) are emerging as new diagnostic tools for COVID-19 and real-world evaluations are needed to establish their performance characteristics.

Main objective

To evaluate the accuracy of the Panbio™ Ag-RDT at primary health care (PHC) centers and test sites in symptomatic patients and close contacts, using the Reverse-Transcription Polymerase Chain Reaction (RT-PCR) test as the gold standard.

Methods

This was a prospective diagnostic study conducted in four PHC centers and two test sites in Mallorca, Spain. Consecutive patients older than 18 years, attending the sites for RT-PCR testing either for suggestive symptoms of infection or a close contact, were included. Two nasopharyngeal samples were collected, one for RT-PCR and the other was processed on-site using the Panbio™ rapid antigen test kit for SARS-CoV-2. The sensitivity and specificity were calculated using RT-PCR as the reference, and the predictive values using the pretest probability results for each analyzed group.

Results

A total of 1369 participants were included; mean age 42.5 ± 14.9 years and 54.3% women. The overall prevalence was 10.2%. Most participants (70.6%) presented within 5 days of the onset of symptoms or close contact, and more than 70% had high viral loads. The overall sensitivity was of 71.4% (95% CI: 63.1%, 78.7%), the specificity of 99.8% (95% CI: 99.4%, 99.9%), the positive predictive value of 98.0% (95% CI: 93.0%, 99.7%) and a negative predictive value of 96.8% (95% CI: 95.7%, 97.7%). The sensitivity was higher in symptomatic patients, in those arriving within 5 days since symptom onset and in those with high viral load.

Conclusion

Ag-RDT had relatively good performance characteristics in suspected symptomatic patients within five days since the onset of symptoms. However, our results concludes that a negative Ag-RDT in these settings must be considered as presumptive.
Role of air temperature and humidity in the transmission of SARS-CoV-2 in the United States
Authors: Ma Yiqun , Pei Sen , Shaman Jeffrey , Dubrow Robert , Chen Kai
Published: November 2020

Improved understanding of the effects of meteorological conditions on the transmission of SARS-CoV-2, the causative agent for COVID-19 disease, is urgently needed to inform mitigation efforts. Here, we estimated the relationship between air temperature or specific humidity (SH) and SARS-CoV-2 transmission in 913 U.S. counties with abundant reported infections from March 15 to August 31, 2020. Specifically, we quantified the associations of daily mean temperature and SH with daily estimates of the SARS-CoV-2 reproduction number (Rt) and calculated the fraction of Rt attributable to these meteorological conditions. Both lower temperature and lower SH were significantly associated with increased Rt. The fraction of Rt attributable to temperature was 5.10% (95% eCI: 5.00 - 5.18%), and the fraction of Rt attributable to SH was 14.47% (95% eCI: 14.37 - 14.54%). These fractions generally were higher in northern counties than in southern counties. Our findings indicate that cold and dry weather are moderately associated with increased SARS-CoV-2 transmissibility, with humidity playing a larger role than temperature.
Integrating deep learning and unbiased automated high-content screening to identify complex disease signatures in human fibroblasts
Authors: Schiff Lauren , Migliori Bianca , Chen Ye , Carter Deidre , Bonilla Caitlyn , Hall Jenna , Fan Minjie , Tam Edmund , Ahadi Sara , Fischbacher Brodie , Geraschenko Anton , Hunter Christopher J. , Venugopalan Subhashini , DesMarteau Sean , Narayanaswamy Arunachalam , Jacob Selwyn , Armstrong Zan , Ferrarotto Peter , Williams Brian , Buckley-Herd Geoff , Hazard Jon , Goldberg Jordan , Coram Marc , Otto Reid , Baltz Edward A. , Andres-Martin Laura , Pritchard Orion , Duren-Lubanski Alyssa , Daigavane Ameya , Reggio Kathryn ,   NYSCF Global Stem Cell Array® Team, Nelson Phillip C. , Frumkin Michael , Solomon Susan L. , Bauer Lauren , Aiyar Raeka S. , Schwarzbach Elizabeth , Noggle Scott A. , Monsma Frederick J. , Paull Daniel , Berndl Marc , Yang Samuel J. , Johannesson Bjarki
Published: November 2020

Drug discovery for diseases such as Parkinson’s disease are impeded by the lack of screenable cellular phenotypes. We present an unbiased phenotypic profiling platform that combines automated cell culture, high-content imaging, Cell Painting, and deep learning. We applied this platform to primary fibroblasts from 91 Parkinson’s disease patients and matched healthy controls, creating the largest publicly available Cell Painting image dataset to date at 48 terabytes. We use fixed weights from a convolutional deep neural network trained on ImageNet to generate deep embeddings from each image and train machine learning models to detect morphological disease phenotypes. Our platform’s robustness and sensitivity allow the detection of individual-specific variation with high fidelity across batches and plate layouts. Lastly, our models confidently separateLRRK2and sporadic Parkinson’s disease lines from healthy controls (receiver operating characteristic area under curve 0.79 (0.08 standard deviation)), supporting the capacity of this platform for complex disease modeling and drug screening applications.
precisionFDA Truth Challenge V2: Calling variants from short- and long-reads in difficult-to-map regions
Authors: Olson Nathan D. , Wagner Justin , McDaniel Jennifer , Stephens Sarah H. , Westreich Samuel T. , Prasanna Anish G. , Johanson Elaine , Boja Emily , Maier Ezekiel J. , Serang Omar , Jáspez David , Lorenzo-Salazar José M. , Muñoz-Barrera Adrián , Rubio-Rodríguez Luis A. , Flores Carlos , Kyriakidis Konstantinos , Malousi Andigoni , Shafin Kishwar , Pesout Trevor , Jain Miten , Paten Benedict , Chang Pi-Chuan , Kolesnikov Alexey , Nattestad Maria , Baid Gunjan , Goel Sidharth , Yang Howard , Carroll Andrew , Eveleigh Robert , Bourgey Mathieu , Bourque Guillaume , Li Gen , ChouXian MA , Tang LinQi , YuanPing DU , Zhang ShaoWei , Morata Jordi , Tonda Raúl , Parra Genís , Trotta Jean-Rémi , Brueffer Christian , Demirkaya-Budak Sinem , Kabakci-Zorlu Duygu , Turgut Deniz , Kalay Özem , Budak Gungor , Narcı Kübra , Arslan Elif , Brown Richard , Johnson Ivan J , Dolgoborodov Alexey , Semenyuk Vladimir , Jain Amit , Tetikol H. Serhat , Jain Varun , Ruehle Mike , Lajoie Bryan , Roddey Cooper , Catreux Severine , Mehio Rami , Ahsan Mian Umair , Liu Qian , Wang Kai , Sahraeian Sayed Mohammad Ebrahim , Fang Li Tai , Mohiyuddin Marghoob , Hung Calvin , Jain Chirag , Feng Hanying , Li Zhipan , Chen Luoqi , Sedlazeck Fritz J. , Zook Justin M.
Published: November 2020

The precisionFDA Truth Challenge V2 aimed to assess the state-of-the-art of variant calling in difficult-to-map regions and the Major Histocompatibility Complex (MHC). Starting with FASTQ files, 20 challenge participants applied their variant calling pipelines and submitted 64 variant callsets for one or more sequencing technologies (~35X Illumina, ~35X PacBio HiFi, and ~50X Oxford Nanopore Technologies). Submissions were evaluated following best practices for benchmarking small variants with the new GIAB benchmark sets and genome stratifications. Challenge submissions included a number of innovative methods for all three technologies, with graph-based and machine-learning methods scoring best for short-read and long-read datasets, respectively. New methods out-performed the 2016 Truth Challenge winners, and new machine-learning approaches combining multiple sequencing technologies performed particularly well. Recent developments in sequencing and variant calling have enabled benchmarking variants in challenging genomic regions, paving the way for the identification of previously unknown clinically relevant variants.