bluuebunny/crossref_metadata_2025 huggingface dataset:
IL-15 and sMAdCAM: Novel roles in COVID-19 pathogenesis
Authors: Singh Amit Kumar , Kasarpalkar Nandini , Bhowmick Shilpa , Paradkar Gaurav , Talreja Mayur , Shah Karan , Tiwari Abhishek , Palav Harsha , Kaginkar Snehal , Kulkarni Rajiv , Patil Ashwini , Kalsurkar Varsha , Agrawal Sachee , Shastri Jayanthi , Dere Rajesh , Bharmal Ramesh , Mahale Smita D. , Bhor Vikrant M. , Patel Vainav
Published: March 2021

Immune cell dysregulation and lymphopenia characterize COVID-19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study we evaluated the association of circulating IL-6, soluble mucosal addressin cell adhesion molecule (sMAdCAM) and IL-15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID-19. A cohort of SARS-CoV-2 infected individuals (n=125) at various stages of disease progression together with healthy controls (n=16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in-depth immune subset characterization and to measure plasma IL-6 levels. sMAdCAM, IL-15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells was observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL-6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho-depletion suggesting opposing roles in pathogenesis. Interestingly, IL-15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, negative association of plasma IL-15 with depleted T, B and NK subsets suggested a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL-15 and IL-6, but not sMAdCAM, were associated with longer duration of hospitalization.
A two-stage super learner for healthcare expenditures
Authors: Wu Ziyue , Berkowitz Seth , Heagerty Patrick , Benkeser David
Published: March 2021

Objective

To improve the estimation of healthcare expenditures by introducing a novel estimation method that is well-suited to situations where data exhibit strong skewness and zero-inflation.

Data Sources

Simulations, and two sources of real-world data: the 2016-2017 Medical Expenditure Panel Survey (MEPS) and the Back Pain Outcomes using Longitudinal Data (BOLD) datasets.

Study Design

Super learner is an ensemble machine learning approach that can combine several algorithms in order to improve estimation. We propose a two-stage super learner that is well suited for use with healthcare expenditure data by separately estimating the probability of any healthcare expenditure and the mean amount of healthcare expenditure conditional on having healthcare expenditures. These estimates can be combined to yield a single estimate of expenditures for each observation. The method can flexibly incorporate a range of individual estimation approaches for each stage of estimation, including both regression-based approaches and machine learning algorithms such as random forests. We compare the performance of the proposed two-stage super learner with a one-stage super learner, and with multiple individual algorithms for estimation of healthcare cost under a broad range of data settings in simulated and real data. The predictive performance of alternative strategies was compared using Mean Squared Error and R2.

Principal Findings

Our results indicate that the two-stage super learner has better performance compared with a one-stage super learner and individual algorithms, for healthcare cost estimation under a wide variety of settings in both simulations and empirical analyses. The improvement of the two-stage super learner over the one-stage super learner was particularly evident in settings when zero-inflation is high.

Conclusions

The two-stage super learner provides researchers an effective approach for healthcare cost analyses in environments where they cannot know the best single algorithm a priori.
Forecasting the Spreading Trajectory of the COVID-19 Pandemic
Authors: Cheng Baolian , Wang Yi-Ming
Published: March 2021

Predictively forecasting future developments for the spread of the COVID-19 pandemic is extremely challenging. A recently published logistic mathematic model has achieved good predictions for infections weeks ahead. In this short communication, we summarize the Logistic spread model, which describes the dynamics of the pandemic evolution and the impacts of people social behavior in fighting against the pandemic. The new pandemic model has two parameters (i.e., transmission rate γ and social distancing d) to be calibrated to the data from the pandemic regions in the early stage of the outbreak while the social distancing is put in place. The model is capable to make early predictions about the spreading trajectory in the communities of any size (countries, states, counties and cities) including the total infections, the date of peak daily infections and the date of the infections reaching a plateau if the testing is sufficient. The results are in good agreement with data and have important applications for ongoing outbreaks and similar infectious disease pandemics in the future.
A randomized controlled trial of a video intervention shows evidence of increasing COVID-19 vaccination intention
Authors: Witus Leah S. , Larson Erik
Published: March 2021

Increasing acceptance of COVID-19 vaccines is imperative for public health, as unvaccinated individuals may impede the ability to reach herd immunity. Previous research on educational interventions to overcome vaccine hesitancy have shown mixed effects in increasing vaccination intention, although much of this work has focused on parental attitudes toward childhood vaccination. In this study, we conducted a randomized controlled trial to investigate whether vaccination intention changes after viewing an animated YouTube video explaining how COVID-19 mRNA vaccines work. We exposed participants to one of four interventions – watching the video with a male narrator, watching the same video with a female narrator, reading the text of the transcript of the video, or receiving no information (control group). We found that participants who watched the version of the video with a male narrator expressed statistically significant increased vaccination intention compared to the control group. The video with a female narrator had more variation in results. As a whole, there was a non-significant increased vaccination intention when analyzing all participants who saw the video with a female narrator; however, for politically conservative participants there was decreased vaccination intention for this intervention, particularly at a threshold between being currently undecided and expressing probable interest. These results are encouraging for the ability of interventions as simple as YouTube videos to increase vaccination propensity, although the inconsistent response to the video with a female narrator demonstrates the potential for bias to affect how certain groups respond to different messengers.

Significance Statement

Widespread vaccination is important for ending the COVID-19 pandemic. This study investigates whether communicating the science behind new COVID-19 vaccines can increase people’s willingness to get vaccinated. We examined the effectiveness of an eight-minute animated video explaining how COVID-19 mRNA vaccines work, varying between a male narrator, a female narrator, and a control group. Participants who saw the video with a male narrator expressed a greater intent to get vaccinated than the control group. Participants who saw the video with a female narrator had more varied responses, including a decreased intent to get vaccinated among political conservatives. These findings indicate that science education may help increase vaccine uptake, but that beliefs about gender may influence how people receive such information.
Long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 are differentially expressed in severe COVID-19 patients: An integrated single cell analysis
Authors: Huang Kai , Wang Catherine , Vagts Christen , Raguveer Vanitha , Finn Patricia W. , Perkins David L.
Published: March 2021

Hyperactive and damaging inflammation is a hallmark of severe rather than mild COVID-19 syndrome. To uncover key inflammatory differentiators between severe and mild COVID-19 disease, we applied an unbiased single-cell transcriptomic analysis. We integrated a bronchoalveolar lavage (BAL) dataset with a peripheral blood mononuclear cell dataset (PBMC) and analyzed the combined cell population, focusing on genes associated with disease severity. Distinct cell populations were detected in both BAL and PBMC where the immunomodulatory long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 were highly differentially expressed between mild and severe patients. The detection of other severity associated genes involved in cellular stress response and apoptosis regulation suggests that the pro-inflammatory functions of these lncRNAs may foster cell stress and damage. The lncRNAs NEAT1 andMALAT1 are potential components of immune dysregulation in COVID-19 that may provide targets for severity related diagnostic measures or therapy.
Involvement of denervated midbrain-derived factors in the formation of ectopic cortico-mesencephalic projection after hemispherectomy
Authors: Chang Leechung , Masada Mayuko , Kojima Masami , Yamamoto Nobuhiko
Published: March 2021

Neuronal remodeling after brain injury is essential for functional recovery. After unilateral cortical lesion, axons from the intact cortex ectopically project to the denervated midbrain to compensate for the lost function, but the underlying molecular mechanisms remain largely unknown. To address this issue, we examined gene expression profiles in denervated and intact mouse midbrains after hemispherectomy at P6, when ectopic contralateral projection occurs robustly. The analysis showed that various axon growth-related genes were upregulated in the denervated midbrain, and most of these genes are reportedly expressed by astrocytes or microglia. To identify the underlying molecules, the receptors for candidate upregulated molecules were knocked out in layer 5 projection neurons in the intact cortex, using the CRISPR/Cas9-mediated method, and axonal projection from the knocked-out cortical neurons was examined after hemispherectomy. We found that the ectopic projection was significantly reduced when integrin subunit beta 3 (Itgb3) or neurotrophic receptor tyrosine kinase 2 (Ntrk2, also known as TrkB) was knocked out. Overall, the present study suggests that midbrain-derived glial factors whose expression is upregulated after hemispherectomy are involved in lesion-induced remodeling of the cortico-mesencephalic projection.
Axon guidance modalities in CNS regeneration revealed by quantitative proteomic analysis
Authors: Vilallongue Noemie , Schaeffer Julia , Hesse Anne Marie , Delpech Céline , Paccard Antoine , Couté Yohan , Belin Stephane , Nawabi Homaira
Published: March 2021

Long-distance regeneration of the central nervous system (CNS) has been achieved from the eye to the brain through activation of neuronal molecular pathways or pharmacological approaches. Unexpectedly, most of the regenerative fibers display guidance defects, which prevents reinnervation and further functional recovery. Therefore, characterizing the mature neuronal environment is essential to understand the adult axonal guidance in order to complete the circuit reconstruction. To this end, we used mass spectrometry to characterize the proteomes of major nuclei of the adult visual system: suprachiasmatic nucleus (SCN), ventral and dorsal lateral geniculate nucleus (vLGN, dLGN) and superior colliculus (SCol)), as well as the optic chiasm. These analyses revealed the presence of guidance molecules and guidance-associated factors in the adult visual targets. Moreover, by performing bilateral optic nerve crush, we showed that the expression of some proteins was significantly modulated by the injury in the visual targets, even in the ones most distal to the lesion site. On another hand, we found that the expression of guidance molecules was not modified upon injury. This implies that these molecules may possibly interfere with the reinnervation of the brain targets. Together, our results provides an extensive characterization of the molecular environment in intact and injured conditions. These findings open new ways to correct regenerating axon guidance notably by manipulating the expression of the corresponding guidance receptors in the nervous system.
Discovery of signatures of fatal neonatal illness in vital signs using highly comparative time-series analysis
Authors: Niestroy Justin C , Moorman J Randall , Levinson Maxwell A , Al Manir Sadnan , Clark Timothy W , Fairchild Karen D , Lake Douglas E
Published: March 2021

Objective

To seek new signatures of illness in heart rate and oxygen saturation vital signs from Neonatal Intensive Care Unit (NICU), we implemented highly comparative time-series analysis to discover features of all-cause mortality in the next 7 days.

Design

We collected 0.5Hz heart rate and oxygen saturation vital signs of infants in the University of Virginia NICU from 2009 to 2019. We applied 4988 algorithmic operations from 11 mathematical families to random daily ten-minute segments. We clustered the results and selected a representative from each, and examined multivariable logistic regression models.

Setting

Neonatal ICU

Patients

5957 NICU infants; 205 died.

Measurements and main results

3555 operations were usable; 20 cluster medoids held more than 81% of the information. A multivariable model had AUC 0.83. Five algorithms outperformed others: moving threshold, successive increases, surprise, and random walk. We computed provenance of the computations and constructed a software library with links to the data.

Conclusions

Highly comparative time-series analysis revealed new vital sign measures to identify NICU patients at the highest risk of death in the next week.
TPST-dependent and -independent regulation of root development and signaling by PSK LRR receptor kinases in Arabidopsis
Authors: Kaufmann Christine , Stührwohldt Nils , Sauter Margret
Published: March 2021

Tyrosine-sulfated peptides are key regulators of plant growth and development. The disulfated pentapeptide phytosulfokine (PSK) mediates growth via leucine-rich repeat receptor-like kinases, PSKR1 and PSKR2. PSKRs are part of a response module at the plasma membrane that mediates short-term growth responses, but downstream signaling of transcriptional regulation remains unexplored. In Arabidopsis, tyrosine sulfation is catalyzed by a single-copy gene (TPST). We performed a microarray-based transcriptome analysis in thetpst-1mutant background that lacks sulfated peptides to identify PSK-regulated genes and genes that are regulated by other sulfated peptides. Of the 160 PSK-regulated genes, several had functions in root growth and development in agreement with shorter roots and a higher lateral root density intpst-1. Further,tpst-1roots developed higher numbers of root hairs and PSK induced expression ofWEREWOLF (WER), its paralogMYB DOMAIN PROTEIN 23 (MYB23)andAt1g66800that maintain non-hair cell fate. Thetpst-1 pskr1-3 pskr2-1mutant showed even shorter roots, and higher lateral root and root hair density thantpst-1revealing unexpected synergistic effects of ligand and PSK receptor deficiencies. While residual activities may exist, overexpression ofPSKR1in thetpst-1background induced root growth suggesting that PSKR1 may be active in the absence of sulfated ligands.

Highlight

Phytosulfokine (PSK) receptor signaling promotes root elongation, determines lateral root density and maintains non-hair cell fate partially independent of TPST responsible for the activating sulfation of PSK.
RENANO: a REference-based compressor for NANOpore FASTQ files
Authors: Álvarez Guillermo Dufort y , Seroussi Gadiel , Smircich Pablo , Sotelo-Silveira José , Ochoa Idoia , Martín Álvaro
Published: March 2021

Nanopore sequencing technologies are rapidly gaining popularity, in part, due to the massive amounts of genomic data they produce in short periods of time (up to 8.5 TB of data in less than 72 hours). In order to reduce the costs of transmission and storage, efficient compression methods for this type of data are needed. Unlike short-read technologies, nanopore sequencing generates long noisy reads of variable length. In this note we introduce RENANO, a reference-based lossless FASTQ data compressor, specifically tailored to compress FASTQ files generated with nanopore sequencing technologies. RENANO builds on the recent compressor ENANO, which is the current state of the art. RENANO focuses on improving the compression of the base call sequence portion of the FASTQ file, leaving the other parts of ENANO intact. Two novel reference-based compression algorithms are introduced, contemplating different scenarios: in the first scenario, a reference genome is available without cost to both the compressor and the decompressor; in the second, the reference genome is availableonlyon the compressor side, and a compacted version of the reference is transmitted to the decompressor as part of the compressed file. To evaluate the proposed algorithms, we compare RENANO against ENANO on several publicly available nanopore datasets. In the first scenario considered, RENANO improves the base call sequences compression of ENANO by 39.8%, on average, over all the datasets. As for total compression (including the other parts of the FASTQ file), the average improvement is 12.7%. In the second scenario considered, the base call compression improvements of RENANO over ENANO range from 15.2% to 49.0%, depending on the coverage of the compressed dataset, while in terms of total size, the improvements range from 5.1% to 16.5%.

Implementations of the proposed algorithms are freely available for download athttps://github.com/guilledufort/RENANO.
The phosphate starvation response recruits the TOR pathway to regulate growth in Arabidopsis cell cultures
Authors: Dobrenel Thomas , Kushwah Sunita , Mubeen Umarah , Jansen Wouter , Delhomme Nicolas , Caldana Camila , Hanson Johannes
Published: March 2021

Abstract

In eukaryotes, TOR (Target Of Rapamycin) is a conserved regulator of growth that integrates both endogenous and exogenous signals. These signals include the internal nutritional status, and in plants, TOR has been shown to be regulated by carbon, nitrogen and sulfur availability. In this study, we show that in Arabidopsis the TOR pathway also integrates phosphorus availability to actively modulate the cell cycle, which in turn regulates the intracellular content of amino acids and organic acids. We observed a substantial overlap between the phenotypic, metabolic and transcriptomic responses of TOR inactivation and phosphorus starvation in Arabidopsis cell culture. Although phosphorus availability modulates TOR activity, changes in the levels of TOR activity do not alter the expression of marker genes for phosphorus status. These data prompted us to place the sensing of phosphorus availability upstream of the modulation of TOR activity which, in turn, regulates the cell cycle and primary metabolism to adjust plant growth in plants.
Subthalamic-Cortical Network Reorganization during Parkinson’s Tremor
Authors: Lauro Peter M. , Lee Shane , Akbar Umer , Asaad Wael F.
Published: March 2021

Tremor, a common and often primary symptom of Parkinson’s disease, has been modeled with distinct onset and maintenance dynamics. To identify the neurophysiologic correlates of each state, we acquired intraoperative cortical and subthalamic nucleus recordings from ten patients performing a naturalistic visual-motor task. From this task we isolated short epochs of tremor onset and sustained tremor. Comparing these epochs, we found that the subthalamic nucleus was central to tremor onset, as it drove both motor cortical activity and tremor output. Once tremor became sustained, control of tremor shifted to cortex. At the same time, changes in directed functional connectivity across sensorimotor cortex further distinguished the sustained tremor state.

SIGNIFICANCE STATEMENT

Tremor is a common symptom of Parkinson’s disease (PD). While tremor pathophysiology is thought to involve both basal ganglia and cerebello-thalamic-cortical circuits, it is unknown how these structures functionally interact to produce tremor. In this manuscript, we analyzed intracranial recordings from the subthalamic nucleus and sensorimotor cortex in patients with PD undergoing deep brain stimulation (DBS) surgery. Using an intraoperative task, we examined tremor in two separate dynamic contexts: when tremor first emerged, and when tremor was sustained. We believe that these findings reconcile several models of Parkinson’s tremor, while describing the short-timescale dynamics of subcortical-cortical interactions during tremor for the first time. These findings may describe a framework for developing proactive and responsive neurostimulation models for specifically treating tremor.
Building the Mega Single Cell Transcriptome Ocular Meta-Atlas
Authors: Swamy Vinay S , Fufa Temesgen D , Hufnagel Robert B , McGaughey David M
Published: March 2021

The development of highly scalable single cell transcriptome technology has resulted in the creation of thousands of datasets, over 30 in the retina alone. Analyzing the transcriptomes between different projects is highly desirable as this would allow for better assessment of which biological effects are consistent across independent studies. However it is difficult to compare and contrast data across different projects as there are substantial batch effects from computational processing, single cell technology utilized, and the natural biological variation. While many single cell transcriptome specific batch correction methods purport to remove the technical noise it is difficult to ascertain which method functions works best. We developed a lightweight R package (scPOP) that brings in batch integration methods and uses a simple heuristic to balance batch merging and celltype/cluster purity. We use this package along with a Snakefile based workflow system to demonstrate how to optimally merge 766,615 cells from 33 retina datsets and three species to create a massive ocular single cell transcriptome meta-atlas. This provides a model how to efficiently create meta-atlases for tissues and cells of interest.
Tactile spatial discrimination on the torso using vibrotactile and force stimulation
Authors: Fadaei J. Atena , Franza Matteo , Kannape Oliver Alan , Hara Masayuki , Blanke Olaf
Published: March 2021

There is a steadily growing number of mobile communication systems that provide spatially encoded tactile information to the humans’ torso. However, the increased use of such hands-off displays is currently not matched with or supported by systematic perceptual characterization of tactile spatial discrimination on the torso. Furthermore, there are currently no data testing spatial discrimination for dynamic force stimuli applied to the torso. In the present study, we measured tactile point localization (PL) and tactile direction discrimination (DD) on the thoracic spine using two unisex torso-worn tactile vests realized with arrays of 3×3 vibrotactile or force feedback actuators. We aimed to, firstly, evaluate and compare the spatial discrimination of vibrotactile and force stimulations on the thoracic spine and, secondly, to investigate the relationship between the PL and DD results across stimulations. Thirty-four healthy participants performed both tasks with both vests. Tactile accuracies for vibrotactile and force stimulations were 60.7% and 54.6% for the PL task; 71.0% and 67.7% for the DD task, respectively. Performance correlated positively with both stimulations, although accuracies were higher for the vibrotactile than for the force stimulation across tasks, arguably due to specific properties of vibrotactile stimulations. We observed comparable directional anisotropies in the PL results for both stimulations; however, anisotropies in the DD task were only observed with vibrotactile stimulations. We discuss our findings with respect to tactile perception research as well as their implications for the design of high-resolution torso-mounted tactile displays for spatial cueing.
Optimized hip-knee-ankle exoskeleton assistance at a range of walking speeds
Authors: Bryan Gwendolyn M. , Franks Patrick W. , Song Seungmoon , Voloshina Alexandra S. , Reyes Ricardo , O’Donovan Meghan P. , Gregorczyk Karen N. , Collins Steven H.
Published: March 2021

Background

Effective autonomous exoskeletons will need to be useful at a variety of walking speeds, but we do not know how optimal exoskeleton assistance should change with speed. Optimal exoskeleton assistance may increase with speed similar to biological torque changes or a well-tuned assistance profile may be effective at a variety of speeds.

Methods

We optimized hip-knee-ankle exoskeleton assistance to reduce metabolic cost for three participants walking at 1.0 m/s, 1.25 m/s and 1.5 m/s. We measured metabolic cost, muscle activity, exoskeleton assistance and kinematics. We performed two tailed paired t-tests to determine significance.

Results

Exoskeleton assistance reduced the metabolic cost of walking compared to wearing the exoskeleton with no torque applied by 26%, 47% and 50% at 1.0, 1.25 and 1.5 m/s, respectively. For all three participants, optimized exoskeleton ankle torque was the smallest for slow walking, while hip and knee torque changed slightly with speed in ways that varied across participants. Total applied positive power increased with speed for all three participants, largely due to increased joint velocities, which consistently increased with speed.

Conclusions

Exoskeleton assistance is effective at a range of speeds and is most effective at medium and fast walking speeds. Exoskeleton assistance was less effective for slow walking, which may explain the limited success in reducing metabolic cost for patient populations through exoskeleton assistance. Exoskeleton designers may have more success when targeting activities and groups with faster walking speeds. Speed-related changes in optimized exoskeleton assistance varied by participant, indicating either the benefit of participant-specific tuning or that a wide variety of torque profiles are similarly effective.
Every cog and wheel: Identifying biocomplexity at the genomic and phenotypic level in a population complex of Chinook salmon
Authors: O’Leary Shannon J. , Thompson Tasha Q. , Meek Mariah H.
Published: March 2021

Genomic diversity is the fundamental building block of biodiversity and the necessary ingredient for adaptation. Our rapidly increasing ability to quantify functional, compositional, and structural genomic diversity of populations forces the question of how to balance conservation goals – should the focus be on important functional diversity and key life history traits or on maximizing genomic diversity as a whole? Specifically, the intra-specific diversity (biocomplexity) comprised of phenotypic and genetic variation can determine the ability of a population to respond to changing environmental conditions. Here, we explore the biocomplexity of California’s Central Valley Chinook salmon (Oncorhynchus tshawytscha) population complex at the genomic level. Notably, despite apparent gene flow among individuals with the same migration (life history) phenotypes inhabiting different tributaries, each group is characterized by a surprising component of unique genomic diversity. Our results emphasize the importance of formulating conservation goals focused on maintaining biocomplexity at both the phenotypic and genotypic level. Doing so will maintain the species’ adaptive potential and increase the probability of persistence of the population complex despite changing environmental pressures.
Swimming kinematics and performance of spinal transected lampreys with different levels of axon regeneration
Authors: Fies Jacob. , Gemmell Brad J. , Fogerson Stephanie M. , Costello John H. , Morgan Jennifer R. , Tytell Eric D. , Colin S. P.
Published: March 2021

Neural and functional recovery in lampreys from spinal cord transection has been well documented. However, the extent of axon regeneration is highly variable and it is not known whether it is related to the level of behavioral recovery. To address this, we examined how swimming kinematics were related to axon regeneration by quantifying the relationship between swimming performance and percent axon regeneration of transected lampreys after 11 weeks of recovery. We found that swimming speed was not related to percent axon regeneration but it was closely related to body wave frequency and speed. However, wave frequency and speed varied greatly within individuals which resulted in swimming speed also varying within individuals. In fact, most recovered individuals, regardless of percent axon regeneration, could swim at fast and slow speeds. However, none of the transected individuals were able to generate body waves as large as the control lampreys. In order to swim faster, transected lampreys increased their wave frequencies and, as a result, transected lampreys had much higher frequencies than control lamprey at comparable swimming velocities. These data suggest that the control lampreys swam more efficiently than transected lampreys. In conclusion, there appears to be a minimal recovery threshold in terms of percent axon regeneration required for lampreys to be capable of swimming, however, there also seems to be a limit to how much they can behaviorally recover.
Identifying key federal, state and private lands strategies for achieving 30x30 in the US
Authors: Dreiss Lindsay M. , Malcom Jacob W.
Published: March 2021

Achieving ambitious conservation goals to conserve at least 30% of US lands and waters by 2030 (“30x30”) will require a multi-scale baseline understanding of current protections, key decision makers, and policy tools for moving forward. To help conservationists and decision makers support the science-based call to address the biodiversity and climate crises, we analyze the current spatial patterns of imperiled species biodiversity and carbon stores in the U.S. relative to protected areas. Analyses demonstrate that 30x30 is numerically achievable nationally, but high spatial heterogeneity highlights the need for tailored approaches from a mix of authorities at federal, regional, and state scales. Critically, current land protections rarely overlap with areas essential for conserving imperiled species biodiversity and mitigating climate change. Nearly one-fifth of unprotected biodiversity hotspots and carbon-rich areas are also at risk of either land conversion or climate exposure by 2050. We discuss this baseline relative to key policy considerations for making practical, substantive progress toward the goal.
Interfacing Seurat with the R tidy universe
Authors: Mangiola Stefano , Doyle Maria A , Papenfuss Anthony T
Published: March 2021

Motivation

Seurat is one of the most popular software suites for the analysis of single-cell RNA sequencing data. Considering the popularity of the tidyverse ecosystem, which offers a large set of data display, query, manipulation, integration and visualisation utilities, a great opportunity exists to interface the Seurat object with the tidyverse. This gives the large data science community of tidyverse users the possibility to operate with a familiar grammar.

Results

In order to provide Seurat with a tidyverse-oriented interface without compromising on efficiency, we developed tidyseurat, a light-weight adapter to the tidyverse. Cell information is automatically displayed as a tibble abstraction, which interfaces Seurat with dplyr, tidyr, ggplot2 and plotly packages powering efficient data manipulation, integration and visualisation. Iterative analyses on data subsets is enabled by interfacing with the popular nest-map framework.

Availability and implementation

The software is freely available atcran.r-project.org/web/packages/tidyseurat/andgithub.com/stemangiola/tidyseurat

Contact

Stefano Mangiola (mangiola.s@wehi.edu.au) and Anthony T Papenfuss (papenfuss@wehi.edu.au).
Exploring biomedical records through text mining-driven complex data visualisation
Authors: Costa Joao Pita , Stopar Luka , Rei Luis , Massri Besher , Grobelnik Marko
Published: March 2021

The recent events in health call for the prioritization of insightful and meaningful information retrieval from the fastly growing pool of biomedical knowledge. This information has its own challenges both in the data itself and in its appropriate representation, enhancing its usability by health professionals. In this paper we present a framework leveraging the MEDLINE dataset and its controlled vocabulary, the MeSH Headings, to annotate and explore health-related documents. The MEDijs system ingests and automatically annotates text documents, extending their legacy metadata with MeSH Headings. It then uses text mining algorithms that enable interactive data visualisations. These allow the user to the exploration of the enriched data made available by the MEDijs system.

CCS CONCEPTS

• Information systems; • Computing methodologies → Machine learning approaches;

ACM Reference Format

Joao Pita Costa, Luka Stopar, Luis Rei, Besher Massri, and Marko Grobelnik. 2018. Exploring biomedical records through text mining-driven complex data visualisation. In Proceedings of SEBILAN ’21: ACM International Workshop on Semantics-enabled Biomedical Literature Analytics (SEBILAN ’21). ACM, New York, NY, USA, 6 pages. https://doi.org/0
Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
Authors: Holt Hayley , Talaei Mohammad , Greenig Matthew , Zenner Dominik , Symons Jane , Relton Clare , Young Katherine S , Davies Molly R , Thompson Katherine N , Ashman Jed , Rajpoot Sultan Saeed , Kayyale Ahmed Ali , Rifai Sarah El , Lloyd Philippa J. , Jolliffe David A. , Finer Sarah , Ilidriomiti Stamatina , Miners Alec , Hopkinson Nicholas S. , Alam Bodrul , Pfeffer Paul E , McCoy David , Davies Gwyneth A , Lyons Ronan A , Griffiths Christopher J , Kee Frank , Sheikh Aziz , Breen Gerome , Shaheen Seif O , Martineau Adrian R
Published: March 2021

Background

Risk factors for severe COVID-19 include older age, male sex, obesity, Black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain.

Methods

We undertook a prospective, population-based cohort study (COVIDENCE UK) from 1stMay 2020 to 5thFebruary 2021. Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted odds ratios (aORs) for associations between potential risk factors and risk of COVID-19.

Findings

We recorded 446 incident cases of COVID-19 in 15,227 participants (2.9%). Increased risk of developing COVID-19 was independently associated with Asian/Asian Britishvs. White ethnicity (aOR 2.31, 95% CI 1.35-3.95), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11-1.43), anyvs. no visits to/from other households in previous week (aOR 1.33, 1.07-1.64), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.01-1.09), frontline occupation excluding health/social carevs. no frontline occupation (aOR 1.49, 1.12-1.98), and raised body mass index (BMI) (aOR 1.51 [1.20-1.90] for BMI 25.0-30.0 kg/m2and 1.38 [1.05-1.82] for BMI >30.0 kg/m2vs. BMI <25.0 kg/m2). Atopic disease was independently associated with decreased risk (aOR 0.76, 0.59-0.98). No independent associations were seen for age, sex, other medical conditions, diet, or micronutrient supplement use.

Interpretation

After rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased risk of developing COVID-19, while atopic disease was associated with decreased risk.

Funding

Barts Charity, Health Data Research UK
Midwifery and nurse staffing of inpatient maternity services – a systematic scoping review of associations with outcomes and quality of care
Authors: Turner Lesley , Griffiths Peter , Kitson-Reynolds Ellen
Published: March 2021

Objective

To undertake a scoping literature review of studies examining the quantitative association between staffing levels and outcomes for mothers, neonates, and staff. The purpose was to understand the strength of the available evidence, the direction of effects, and to highlight gaps for future research.

Data Sources

Systematic searches were conducted in Medline (Ovid), Embase (Ovid), CINAHL (EBCSCO), Cochrane Library, TRIP, Web of Science and Scopus.

Study Selection and Review methods

To be eligible, staffing levels had to be quantified for in-patient settings, such as ante-natal, labour/delivery or post-natal care. Staff groups include registered midwives, nurse midwives or equivalent, and assistant staff working under the supervision of registered professionals. Studies of the quality of care, patient outcomes and staff outcomes were included. All quantitative designs were included, including controlled trials, time series, cross-sectional, cohort studies and case controlled studies.

Data were extracted and sources of bias identified by considering the study design, measurement of exposure and outcomes, and risk adjustment. Studies were grouped by outcome noting the direction and significance of effects.

Results

The search yielded a total of 3280 records and 21 studies were included in this review. There were three randomised controlled trials, eleven cohort studies, one case control study and six cross sectional studies. Seventeen were multicentre studies and nine of them had over 30,000 participants.

Reduced incidence of epidural use, augmentation, perineal damage at birth, postpartum haemorrhage, maternal readmission, and neonatal resuscitation were associated with increased midwifery staff. Few studies have suggested a negative impact of increasing staffing rates, although a number of studies have found no significant differences in outcomes. Impact on the mode of birth were unclear. Increasing midwifery support staff was not associated with improved patient outcomes. No studies were found on the impact of low staffing levels for the midwifery workforce.

Conclusions and Implications for practice

Although there is some evidence that higher midwifery staffing is associated with improved outcomes, current research is insufficient to inform service planning. Studies mainly reported outcomes relating to labour, highlighting a gap in research evidence for the antenatal and postnatal periods. Further studies are needed to assess the costs and consequences of variations in maternity staffing, including the deployment of maternity care assistants and other staff groups.
The potential of digital health technologies in African context, Ethiopia
Authors: Manyazewal Tsegahun , Woldeamanuel Yimtubezinash , Blumberg Henry M. , Fekadu Abebaw , Marconi Vincent C.
Published: March 2021

The World Health Organization (WHO) recently put forth a Global Strategy on Digital Health 2020 - 2025 with several countries having already achieved key milestones. We aimed to understand whether and how digital health technologies (DHTs) are absorbed in Africa, tracking Ethiopia as a key node. We conducted a systematic review, searching PubMed-MEDLINE, ScienceDirect, African Journals Online, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform databases from inception to 02 February 2021 for studies of any design that investigated the potential of DHTs in clinical or public health practices in Ethiopia. This review was designed to inform our ongoing DHT-enabled randomized controlled trial (RCT) (ClinicalTrials.gov ID: NCT04216420). We found 23,897 potentially-relevant citations, among which 47 studies met the inclusion criteria, comprising a total of 594,999 patients, healthy individuals, and healthcare professionals. The studies involved seven DHTs: mHealth (25 studies, 573,623 participants); electronic health records (13 studies, 4,534 participants); telemedicine (3 studies, 445 participants); cloud-based application (2 studies, 2,382 participants); genomics data (1 study, 47 participants); information communication technology (2 studies, 551 participants), and artificial intelligence (1 study, 13,417 participants). The studies targeted six health conditions: maternal and child health (15), infectious diseases (11), non-communicable diseases (3), dermatitis (1), surgery (3), and general health conditions (14). The outcomes of interest were feasibility, usability, willingness or readiness, effectiveness, quality improvement, and knowledge or attitude towards DHTs. Four studies involved RCTs. The analysis showed that although DHTs are a relatively recent phenomenon in Ethiopia, their potential harnessing clinical and public health practices are highly visible. Their adoption and implementation in full capacity requires more training, access to better devices such as smartphones, and infrastructure. DHTs hold much promise tackling major clinical and public health backlogs and strengthening the healthcare ecosystem in Africa. More RCTs are needed on emerging DHTs including artificial intelligence, big data, cloud, genomics data, cybersecurity, telemedicine, and wearable devices to provide robust evidence of their potential use in such settings and to materialize the WHO’s Global Digital Health Strategy.
Relative burdens of the COVID-19, malaria, tuberculosis, and HIV/AIDS epidemics in sub-Saharan Africa
Authors: Bell David , Hansen Kristian Schultz
Published: March 2021

COVID-19 has had considerable global impact, but in sub-Saharan Africa is one of several infectious disease priorities. Prioritization is normally guided by disease burden, but the highly age-dependent nature of COVID-19 and other infectious diseases makes comparisons challenging unless considered through metrics that incorporate life years lost and time lived in adverse health. We therefore compared 2020 mortality and Disability-Adjusted Life Years lost (DALYs lost) estimates for malaria, tuberculosis, and HIV/AIDS in sub-Saharan African populations with 12+ months of COVID-19 burden (up to end March 2021), applying known age-related mortality to United Nations estimates of age structure. We further compared exacerbations of disease burden predicted from the COVID-19 public health response. Data was derived from public sources, predicted exacerbations derived from those published by international agencies. For sub-Saharan African populations north of South Africa, recorded COVID-19 DALYs lost in 2020 was 3.7%, 2.3%, and 2.4% of those estimated for tuberculosis, HIV/AIDS and malaria respectively. Predicted exacerbations of these comparator diseases were greater than the estimated COVID-19 burden. Including South Africa and Lesotho, COVID-19 DALYs lost were <12% of those for comparator diseases and dominated by them in all age groups below 65 years. The analysis suggests a relatively low impact from COVID-19. While all four epidemics continue, tuberculosis, HIV/AIDS, and malaria remain far greater health priorities based on disease burden. Resource diversion to COVID-19 therefore runs a high risk of increasing the overall disease burden and causing net harm, further increasing global inequities in health and life expectancy.
Tolerance of Wildlife in Protected Area Borderlands
Authors: Merz Leandra , Pienaar Elizabeth F. , Fik Timothy , Muyengwa Shylock
Published: March 2021

Increases in human-wildlife conflict globally threaten human wellbeing and biodiversity conservation. Sustainable solutions that promote coexistence of people and wildlife are needed, especially in human-dominated landscapes surrounding protected areas. People’s attitudes toward wildlife influence their behaviours, including tolerance for human-wildlife interactions, poaching, and habitat degradation. Better understanding of how to improve people’s attitudes toward wildlife is instrumental to promoting coexistence between people and wildlife in shared spaces. Efforts to promote coexistence often fail because they are based on the inaccurate assumption that people’s attitudes towards wildlife are directly and proportionally related to wildlife-based financial incentives and costs. In reality, people’s attitudes towards wildlife are far more complex. We analysed surveys (n=237) from Mozambique to examine people’s attitudes toward wildlife in the buffer zones surrounding protected areas using logistic regression and Getis-Ord hot-spot analysis (GI*). Mozambique, which is under-represented in the wildlife-based research literature, is characterized by extreme poverty and rewilding efforts. We found that most respondents were tolerant of wildlife and tolerance was positively correlated with people’s age, gender, and agreement with rules governing wildlife conservation. People’s tolerance for wildlife was also reinforced if they receive benefits from wildlife and are situated further from the park fence. Predation, human harm, and crop loss were not significant predictors of tolerance. We found no evidence of spatial patterns in tolerance for wildlife. Our results suggest that wildlife conservation programs are more likely to be successful if benefits are distributed equitably and community members are actively involved in decision making.
Mathematical Modeling and Analysis of Mitochondrial Retrograde Signaling Dynamics
Authors: Chiu Shao-Ting , Tseng Wen-Wei , Wei An-Chi
Published: March 2021

Mitochondria, semi-autonomous eukaryotic organelles, participate in energy production and metabolism, making mitochondrial quality control crucial. As most mitochondrial proteins are encoded by nuclear genes, quality control depends on proper mitochondria-nucleus communication, designated mitochondrial retrograde signaling. Early studies focused on retrograde signaling participants and specific gene knockouts. However, mitochondrial signal modulation remains elusive. Using yeast, we simulated signal propagation following mitochondrial damage and proposed a mathematical model based ordinary differential equations. Mitochondrial retrograde signaling decisions were described using a Boolean model. Dynamics were analyzed through an ordinary differential equation-based model and extended to evaluate the model response to noisy damage signals. Simulation revealed localized protein concentration dynamics, including waveforms, frequency response, and robustness under noise. Retrograde signaling is bistable with three localized steady states, and increased damage compromises robustness. We elucidated mitochondrial retrograde signaling, thus providing a basis for drug design against yeast and fungi.

Author Summary

The yeast RTG pathway regulates mitochondrial metabolism and mitochondrial quality through passing mitochondrial signal to the nucleus to modulate gene expressions. Using microscopic data of RTG proteins translocation from cytosol to nucleus, the parameters were found by fitting 16 knockout conditions simulated from the proposed differential equation-based model. Further, through dose response, ultrasensitivity, frequency response and noise interference, we demonstrated a switch-like property of RTG pathway activation, a capacity charging property of RTG protein translocation, a low pass filter property of signals in different frequencies, and noise amplification due to mitochondrial signal. The proposed mathematical model enables us to understand the dynamics and mechanisms in mitochondrial retrograde signaling in yeast and provides potential antifungal treatment strategies.