bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse driving behaviors are associated with sleep apnea severity and age in cognitively normal older adults at risk for Alzheimer’s disease
Authors: Doherty Jason M , Roe Catherine M , Murphy Samantha A , Johnson Ann M , Fleischer Ella , Toedebusch Cristina D , Redrick Tiara , Freund David , Morris John C , Schindler Suzanne E , Fagan Anne M , Holtzman David M , Lucey Brendan P , Babulal Ganesh M
Published: March 2022

Alzheimer’s disease (AD) pathology accumulates for decades before the onset of cognitive decline. Cognitively normal individuals with biomarker evidence of AD brain pathology (i.e. biomarker + or preclinical AD) can be differentiated from individuals without AD brain pathology based on naturalistic driving data, such as hard acceleration or braking and speeding, measured using in-vehicle dataloggers. Older adults are at increased risk of injury and death from motor vehicle crashes and driving cessation is also linked to negative health outcomes. Identifying potentially modifiable risk factors that increase driving risk may prolong safe driving in old age. Sleep apnea is associated with adverse driving behaviors across the age span. In this study, we hypothesized that high-risk driving behaviors would be associated with increased sleep apnea severity and AD pathology. We found that higher sleep apnea severity measured by a home sleep apnea test was associated with a higher incidence of adverse driving behaviors even after controlling for multiple confounders (β = 0.24 ± 0.09, p < 0.01). This association was independent of AD biomarker positivity (i.e. increased t-tau/Aβ 42 ratio). Increasing age was associated with a higher likelihood of high-risk driving behaviors in individuals with AD brain pathology (β = 0.12 ± 0.04, p < 0.01), but a lower likelihood in individuals without AD brain pathology (β = −0.06 ± 0.03, p < 0.05). These findings suggest that adverse driving behaviors linked to a higher rate of traffic crashes in older adults are associated with sleep apnea severity and AD pathology even in cognitively unimpaired individuals. Further studies are needed to determine if treatment of sleep apnea decreases high-risk driving behaviors and therefore motor vehicle crashes.
In the footsteps of Albert Calmette: an ecological study of TB, leprosy and potential exposure to wild-type Mycobacterium bovis
Authors: Pépin Jacques , Fox Aicha , LeBlanc Louiselle , De Wals Philippe , Rousseau Marie-Claude
Published: March 2022

Background

One hundred years ago, Albert Calmette developed an avirulent strain of Mycobacterium bovis, but there is no evidence that his BCG strain was more immunogenic than wild-type M. bovis. Geographic variations in BCG efficacy remain ill-understood. We hypothesized that exposure to M. bovis through unpasteurized milk might protect against Mycobacterium tuberculosis and Mycobacterium leprae.

Methods

After excluding high-income countries (with universal milk pasteurization) and microstates, an ecological study comprising 113 countries was conducted. National data were obtained from United Nations agencies and international organizations about milk production per capita (1980–1999) as a proxy for exposure to wild-type M. bovis, TB (2000–2019) and leprosy (2005–2019) incidence, HIV prevalence (2000–2019), human development index (2010), global hunger index (2010), neonatal BCG coverage (1980–1999), urbanization (2000) and temperature (1990–2020). Multiple linear regression analyses were performed using log-transformed variables.

Results

For TB, the association differed by region. An inverse association with milk production was seen in regions outside, but not within, sub-Saharan Africa, after adjustment for confounders. The incidence of leprosy was inversely associated with milk production when combining all countries, but the association was stronger in sub-Saharan Africa.

Conclusions

Exposure to wild-type M. bovis through unpasteurized milk may provide cross-protection against M. tuberculosis and M. leprae and contribute to geographic disparities in BCG efficacy. This needs to be confirmed by individual-level studies.
The Impact of Upper Cervical Spine Alignment on Patient-reported Outcome Measures in Anterior Cervical Decompression and Fusion
Authors: Divi Srikanth N. , Karamian Brian A. , Canseco Jose A. , Chang Michael , Toci Gregory R. , Goyal Dhruv K.C. , Nicholson Kristen J. , Mujica Victor E. , Bronson Wesley , Kaye I. David , Kurd Mark F. , Woods Barrett I. , Radcliff Kris E. , Rihn Jeffrey A. , Anderson D. Greg , Hilibrand Alan S. , Kepler Christopher K. , Vaccaro Alexander R. , Schroeder Gregory D.
Published: March 2022

Study Design:

This was a retrospective cohort study.

Objective:

To determine the extent to which the upper cervical spine compensates for malalignment in the subaxial cervical spine, and how changes in upper cervical spine sagittal alignment affect patient-reported outcomes.

Summary of Background Data:

Previous research has investigated the relationship between clinical outcomes and radiographic parameters in the subaxial cervical spine following anterior cervical discectomy and fusion (ACDF). However, limited research exists regarding the upper cervical spine (occiput to C2), which accounts for up to 40% of neck movement and has been hypothesized to compensate for subaxial dysfunction.

Materials and Methods:

Patients undergoing ACDF for cervical radiculopathy and/or myelopathy at a single center with minimum 1-year follow-up were included. Radiographic parameters including cervical sagittal vertical axis, C0 angle, C1 inclination angle, C2 slope, Occiput-C1 angle (Oc–C1 degrees), Oc–C2 degrees, Oc–C7 degrees, C1–C2 degrees, C1–C7 degrees, and C2–C7 degrees cervical lordosis (CL) were recorded preoperatively and postoperatively. Delta (Δ) values were calculated by subtracting preoperative values from postoperative values. Correlation analysis as well as multiple linear regression analysis was used to determine relationships between radiographic and clinical outcomes. Alpha was set at 0.05.

Results:

A total of 264 patients were included (mean follow-up 20 mo). C2 slope significantly decreased for patients after surgery (Δ=−0.8, P=0.02), as did parameters of regional cervical lordosis (Oc–C7 degrees, C1–C7 degrees, and C2–C7 degrees; P<0.001, <0.001, and 0.01, respectively). Weak to moderate associations were observed between postoperative CL and C1 inclination (r=−0.24, P<0.001), Oc–C1 degrees (r=0.59, P<0.001), and C1–C2 degrees (r=−0.23, P<0.001). Increased preoperative C1–C2 degrees and Oc–C2 degrees inversely correlated with preoperative SF-12 Mental Composite Score (MCS-12) scores (r=−0.16, P=0.01 and r=−0.13, P=0.04). Cervical sagittal vertical axis was found to have weak but significant associations with Short Form-12 (SF-12) Physical Composite Score (PCS-12) (r=−0.13, P=0.03) and MCS-12 (r=0.12, P=0.05).

Conclusion:

No clinically significant relationship between upper cervical and subaxial cervical alignment was detected for patients undergoing ACDF for neurological symptoms. Upper cervical spine alignment was not found to be a significant predictor of patient-reported outcomes after ACDF.

Level of Evidence:

Level III.
Pattern and risk factors of menstrual regulation service use among ever-married women in Bangladesh: evidence from a nationally representative cross-sectional survey
Authors: Alam Md. Rashed , Khan Md. Nuruzzaman , Sawangdee Yothin
Published: March 2022

Background

Around 47% of the total conceptions in Bangladesh are unintended which leads to several adverse consequences, including maternal and child mortality. Availability of menstrual regulation (MR) service and its use can help women to end conception at an earlier stage, as such, reducing adverse consequences related to the unintended pregnancy. We explored the prevalence and determinants of MR service knowledge and its use among ever-married women in Bangladesh.

Methods

A total of 20 127 ever-married women data from the 2017 Bangladesh Demographic and Health Survey were analyzed. Knowledge about menstrual regulation (MR) and its use were our outcomes of interest. Several individual, household and community-level factors were considered as explanatory variables. The multilevel mixed-effects Poisson regression model was used to determine the factors associated with MR service knowledge and its use in Bangladesh.

Results

Around 71% of the total analyzed women reported they know about MR service while only 7% of them reported they used this service within three years of the survey date. MR service knowledge was found to be higher among women with increased age and education and engaged in income-generating employment. Knowledge about MR service was also found to be higher among women whose husbands were higher educated and engaged in physical work or business. Rural women and women who resided in the community with lower poverty and higher illiteracy were reported lower knowledge of MR service. MR service use was found higher among higher-aged women, women whose husbands were either physical workers or businessmen, women who have an increased number of children and inherent in the community with lower poverty. Lower use of MR service was found among women who resided in the Chattogram, Khulna, and Mymensingh divisions and women who resided in the community with increased illiteracy.

Conclusion

Use of MR service is very low in Bangladesh. This could be responsible for higher adverse consequences related to unintended pregnancy including higher maternal and child mortality. Policies and programs are important to aware women of MR.
Beyond inappropriate fire regimes: a synthesis of fire-driven declines of threatened mammals in Australia
Authors: Santos Julianna L. , Hradsky Bronwyn A. , Keith David A. , Rowe Kevin , Senior Katharine L. , Sitters Holly , Kelly Luke T.
Published: March 2022

Fire can promote biodiversity but changing patterns of fire threaten species worldwide. While scientific literature often describes ‘inappropriate fire regimes’ as a significant threat to biodiversity, less attention has been paid to the characteristics that make a fire regime inappropriate. We go beyond this generic description and synthesize how inappropriate fire regimes contribute to declines of animal populations, using threatened mammals as a case study. We developed a demographic framework for classifying mechanisms by which fire regimes cause population decline, and applied the framework in a systematic review to identify fire characteristics and interacting threats associated with population declines in Australian threatened land mammals (n=99). Inappropriate fire regimes threaten 88% of Australian threatened land mammals. Our review indicates that intense, large, and frequent fires are the primary cause of fire-related population declines, particularly through their influence on survival rates. However, several species are threatened by a lack of fire and there is considerable uncertainty in the evidence base for fire-related declines. Climate change and predation are documented or predicted to interact with fire to exacerbate mammalian declines. This demographic framework will help target conservation actions globally and would be enhanced by empirical studies of animal survival, dispersal, and reproduction.
NFAT5 induction by the tumor microenvironment enforces CD8 T cell exhaustion
Authors: Tillé Laure , Cropp Daniela , Bodley Gabrielle , Andreatta Massimo , Charmoy Mélanie , Crespo Isaac , Nassiri Sina , Lourenco Joao , Leblond Marine , Lopez-Rodriguez Cristina , Speiser Daniel E. , Carmona Santiago J. , Held Werner , Verdeil Grégory
Published: March 2022

Persistent exposure to antigen during chronic infection or cancer renders T cells dysfunctional. The molecular mechanisms regulating this state of exhaustion are thought to be common in infection and cancer, despite obvious differences in their microenvironments. We discovered that NFAT5, an NFAT family member lacking an AP-1 docking site, is highly expressed in exhausted T cells from murine and human tumors and is a central player in tumor-induced exhaustion. While NFAT5 overexpression reduced tumor control, NFAT5 deletion improved tumor control by promoting the accumulation of tumor-specific CD8+ T cells that expressed less TOX and PD-1 and produced more cytokines particularly among precursor exhausted cells. Conversely, NFAT5 had no effect on chronic infection-induced T cell exhaustion. Mechanistically we found that TCR triggering induced NFAT5 expression and that hyperosmolarity stimulated transcriptional activity of NFAT5. We propose that NFAT5 takes over NFAT1/2 to promote exhaustion specifically in tumor-infiltrating CD8+ T cells.
Sea anemone Frizzled receptors play partially redundant roles in the oral-aboral axis patterning
Authors: Niedermoser Isabell , Lebedeva Tatiana , Genikhovich Grigory
Published: March 2022

Canonical Wnt (cWnt) signaling is involved in a plethora of basic developmental processes such as endomesoderm specification, gastrulation and patterning the main body axis. To activate the signal, Wnt ligands form complexes with LRP5/6 and Frizzled receptors, which leads to nuclear translocation of β-catenin and transcriptional response. In Bilateria, the expression of different Frizzled genes is often partially overlapping, and their functions are known to be redundant in several developmental contexts. Here we demonstrate that all four Frizzled receptors take part in the cWnt-mediated oral-aboral axis patterning in the cnidarian Nematostella vectensis but show partially redundant functions. However, we do not see evidence for their involvement in the specification of the endoderm – an earlier event likely relying on maternal, intracellular β-catenin signaling components. Finally, we demonstrate that the main Wnt ligands crucial for the early oral-aboral patterning are Wnt3 and Wnt4. Comparison of our data to the knowledge from other models suggests that distinct but overlapping expression domains and partial functional redundancy of cnidarian and bilaterian Frizzled genes may represent a shared ancestral trait.
Tempo: an unsupervised Bayesian algorithm for circadian phase inference in single-cell transcriptomics
Authors: Auerbach Benjamin J. , FitzGerald Garret A. , Li Mingyao
Published: March 2022

The circadian clock is a 24-hour cellular timekeeping mechanism that temporally regulates human physiology. Answering several fundamental questions in circadian biology will require joint measures of single-cell circadian phases and transcriptomes. However, no widespread experimental approaches exist for this purpose. While computational approaches exist to infer cell phase directly from single-cell RNA-sequencing (scRNA-seq) data, existing methods yield poor circadian phase estimates, and do not quantify estimation uncertainty, which is essential for interpretation of results from highly sparse scRNA-seq data. To address these unmet needs, we developed Tempo, a Bayesian variational inference approach that incorporates domain knowledge of the clock and quantifies phase estimation uncertainty. Through simulations and analyses of real data, we demonstrate that Tempo yields more accurate estimates of circadian phase than existing methods and provides well-calibrated uncertainty quantifications. We further demonstrate that these properties generalize to the cell cycle. Tempo will facilitate large-scale studies of single-cell circadian transcription.
TidyMass: An Object-oriented Reproducible Analysis Framework for LC-MS Data
Authors: Shen Xiaotao , Yan Hong , Wang Chuchu , Gao Peng , Johnson Caroline H. , Snyder Michael P.
Published: March 2022

Reproducibility and transparency have been longstanding but significant problems for the metabolomics field. Here, we present the tidyMass project (https://www.tidymass.org/), a comprehensive computational framework that can achieve the shareable and reproducible workflow needs of data processing and analysis for LC-MS-based untargeted metabolomics. TidyMass was designed based on the following strategies to address the limitations of current tools: 1) Cross-platform utility. TidyMass can be installed on all platforms; 2) Uniformity, shareability, traceability, and reproducibility. A uniform data format has been developed, specifically designed to store and manage processed metabolomics data and processing parameters, making it possible to trace the prior analysis steps and parameters; 3) Flexibility and extensibility. The modular architecture makes tidyMass a highly flexible and extensible tool, so other users can improve it and integrate it with their own pipeline easily.
Dynamical Systems Models for Plasma Dilution
Authors: Chambers Dylan , Christensen Neil
Published: March 2022

Recent experiments provide evidence that diluting the blood plasma restores the plasma environment to a more youthful level at least partially restoring the health of organs and tissues throughout the body. We propose that a dynamical-systems model representing the plasma constituents could support the optimization process and help determine the appropriate dilution level, frequency and any simultaneous plasma infusions to achieve the most favorable outcome. We use a combination of a gradient descent, a simulated annealing and a genetic algorithm to find a population of models that fit illustrative data. We analyze this population and present distributions of the model parameters and include a collection of plots of the dilution process for illustrative models. We then consider modifications of the dilution in order to illustrate what predictions might be possible had we more data to disambiguate the model.
Drug mechanism enrichment analysis improves prioritization of therapeutics for repurposing
Authors: Garana Belinda B. , Joly James H. , Delfarah Alireza , Hong Hyunjun , Graham Nicholas A.
Published: March 2022

BACKGROUND

There is a pressing need for improved methods to identify effective therapeutics for disease. Many computational approaches have been developed to repurpose existing drugs to meet this need. However, these tools often output long lists of candidate drugs that are difficult to interpret, and individual drug candidates may suffer from unknown off-target effects. We reasoned that an approach which aggregates information from multiple drugs that share a common mechanism of action (MOA) would increase on-target signal compared to evaluating drugs on an individual basis. In this study, we present Drug Mechanism Enrichment Analysis (DMEA), an adaptation of Gene Set Enrichment Analysis (GSEA), which groups drugs with shared MOAs to improve the prioritization of drug repurposing candidates.

RESULTS

First, we tested DMEA on simulated data and showed that it can sensitively and robustly identify an enriched drug MOA. Next, we used DMEA on three types of rank-ordered drug lists: (1) perturbagen signatures based on gene expression data, (2) drug sensitivity scores based on high-throughput cancer cell line screening, and (3) molecular classification scores of intrinsic and acquired drug resistance. In each case, DMEA detected the expected MOA as well as other relevant MOAs. Furthermore, the rankings of MOAs generated by DMEA were better than the original single-drug rankings in all tested data sets. Finally, in a drug discovery experiment, we identified potential senescence-inducing and senolytic drug MOAs for primary human mammary epithelial cells and then experimentally validated the senolytic effects of EGFR inhibitors.

CONCLUSIONS

DMEA is a fast and versatile bioinformatic tool that can improve the prioritization of candidates for drug repurposing. By grouping drugs with a shared MOA, DMEA increases on-target signal and reduces off-target effects compared to analysis of individual drugs. DMEA is publicly available as both a web application and an R package athttps://belindabgarana.github.io/DMEA.
Unsupervised discovery of tissue architecture in multiplexed imaging
Authors: Kim Junbum , Rustam Samir , Mosquera Juan Miguel , Randell Scott H. , Shaykhiev Renat , Rendeiro André F. , Elemento Olivier
Published: March 2022

Multiplexed imaging and spatial transcriptomics enable highly resolved spatial characterization of cellular phenotypes, but still largely depend on laborious manual annotation to understand higher-order patterns of tissue organization. As a result, higher-order patterns of tissue organization are poorly understood and not systematically connected to disease pathology or clinical outcomes. To address this gap, we developed UTAG, a novel method to identify and quantify microanatomical tissue structures in multiplexed images without human intervention. Our method combines information on cellular phenotypes with the physical proximity of cells to accurately identify organ-specific microanatomical domains in healthy and diseased tissue. We apply our method to various types of images across physiological and disease states to show that it can consistently detect higher level architectures in human organs, quantify structural differences between healthy and diseased tissue, and reveal tissue organization patterns with relevance to clinical outcomes in cancer patients.
Automated neuron tracking inside moving and deforming animals using deep learning and targeted augmentation
Authors: Park Core Francisco , Keshteli Mahsa Barzegar , Korchagina Kseniia , Delrocq Ariane , Susoy Vladislav , Jones Corinne L. , Samuel Aravinthan D. T. , Rahi Sahand Jamal
Published: March 2022

Advances in functional brain imaging now allow sustained rapid 3D visualization of large numbers of neurons inside behaving animals. To decode circuit activity, imaged neurons must be individually segmented and tracked. This is particularly challenging when the brain itself moves and deforms inside a flexible body. The field has lacked general methods for solving this problem effectively. To address this need, we developed a method based on a convolutional neural network (CNN) Awith specific enhancements which we apply to freely moving Caenorhabditis elegans. For a traditional CNN to track neurons across images of a brain with different postures, the CNN must be trained with ground truth (GT) annotations of similar postures. When these postures are diverse, an adequate number of GT annotations can be prohibitively large to generate manually. We introduce ‘targeted augmentation’, a method to automatically synthesize reliable annotations from a few manual annotations. Our method effectively learns the internal deformations of the brain. The learned deformations are used to synthesize annotations for new postures by deforming the manual annotations of similar postures in GT images. The technique is germane to 3D images, which are generally more difficult to analyze than 2D images. The synthetic annotations, which are added to diversify training datasets, drastically reduce manual annotation and proofreading. Our method is effective both when neurons are represented as individual points or as 3D volumes. We provide a GUI that incorporates targeted augmentation in an end-to-end pipeline, from manual GT annotation of a few images to final proofreading of all images. We apply the method to simultaneously measure activity in the second-layer interneurons in C. elegans: RIA, RIB, and RIM, including the RIA neurite. We find that these neurons show rich behaviors, including switching entrainment on and off dynamically when the animal is exposed to periodic odor pulses.
Targeted Anatomical and Functional Identification of Antinociceptive and Pronociceptive Serotonergic Neurons that Project to the Spinal Dorsal Horn
Authors: Ganley Robert P. , Magalhaes de Sousa Marília , Werder Kira , Öztürk Tugce , Mendes Raquel , Ranucci Matteo , Wildner Hendrik , Zeilhofer Hanns Ulrich
Published: March 2022

Spinally-projecting serotonergic neurons play a key role in controlling pain sensitivity and can either increase or decrease nociception depending on physiological context. It is currently unknown how serotonergic neurons mediate these opposing effects. Utilizing virus-based strategies, we identified two anatomically separated populations of serotonergic hindbrain neurons located in the lateral paragigantocellularis (LPGi) and the medial hindbrain, which respectively innervate the superficial and deep spinal dorsal horn and have contrasting effects on sensory perception. Our tracing experiments revealed that serotonergic neurons of the LPGi were much more susceptible to transduction with spinally injected AAV2retro vectors than medial hindbrain serotonergic neurons. Taking advantage of this difference, we employed intersectional chemogenetic approaches to demonstrate that activation of the LPGi serotonergic projections decreases thermal sensitivity, whereas activation of medial serotonergic neurons increases sensitivity to mechanical von Frey stimulation. Together these results suggest that there are functionally distinct classes of serotonergic hindbrain neurons that differ in their anatomical location in the hindbrain, their postsynaptic targets in the spinal cord, and their impact on nociceptive sensitivity. The LPGi neurons that give rise to rather global and bilateral projections throughout the rostrocaudal extent of the spinal cord appear to be ideally posed to contribute to widespread systemic pain control.
Deep Learning-Derived Myocardial Strain
Authors: Kwan Alan C. , Tokodi Márton , Jain Ishan , Chang Ernest , Theurer John , Tang Xiu , Francisco Nadia , Haddad Francois , Liang David , Yuan Neal , Merkely Béla , Siegel Robert , Cheng Susan , Kovács Attila , Ouyang David
Published: March 2022

Background

Echocardiographic strain measurements require extensive operator experience and have significant inter-vendor variability. This study sought to develop an automated deep learning strain (DLS) analysis pipeline and validate its performance both externally and prospectively.

Methods

The DLS pipeline takes blood pool semantic segmentation results from the EchoNet-Dynamic network and derives longitudinal strain from the frame-by-frame change in the length of the left ventricular endocardial contour. The pipeline was developed using 7,465 echocardiographic videos, with preprocessing steps optimized to determine the change in endocardial length from systole to diastole. It was evaluated on a large external retrospective dataset and was prospectively compared with manual within-patient acquisition of repeated measures by two experienced sonographers and two separate vendor speckle-tracking methods on different machines.

Results

In the external validation set, the DLS method maintained moderate agreement (intraclass correlation coefficient (ICC) 0.58, p<0.001) with a bias of -2.33% (limits of agreement -10.61 to 5.93%). The absolute difference in measurements was independent of subjective image quality (ß: 0.12, SE: 0.10, p=0.21). Compared to readers on repeated measures, our method has reduced variability (standard deviation: 1.35 vs. 2.55%) and better inter-vendor agreement (ICC: 0.45 vs. 0.29).

Conclusions

The DLS measurement provides lower variance than human measurements and similar quantitative results. The method is rapid, consistent, vendor-agnostic, publicly released, and robust across a wide range of imaging qualities.
COVID-19 Vaccine Hesitancy in Ghana: The Roles of Political Allegiance, Misinformation Beliefs, and Sociodemographic Factors
Authors: Brackstone Ken , Atengble Kirchuffs , Head Michael G , Boateng Laud A
Published: March 2022

The vast majority of people in the world who are unvaccinated against COVID-19 reside in LMIC countries in sub-Saharan Africa. This includes Ghana, where only 15.9% of the country are fully vaccinated as of April 2022. A key factor negatively impacting vaccination campaigns is vaccine hesitancy, defined as the delay in the acceptance, or blunt refusal, of vaccines. Four online cross-sectional surveys of Ghanaian citizens were conducted in August 2020 (N = 3048), March 2021 (N = 1558), June 2021 (N = 1295), and February 2022 (N = 424) to observe temporal trends of vaccine hesitancy in Ghana, and to examine key groups associated with hesitancy. Overall hesitancy decreased from 36.8% (95% CI: 35.1%-38.5%) in August 2020 to 17.2% (95% CI: 15.3%-19.1%) in March 2021. However, hesitancy increased to 23.8% (95% CI: 21.5%-26.1%) in June 2021, and then again to 52.2% (95% CI: 47.4%-57.0%) in February 2022. Key reasons included not having enough vaccine-related information (50.6%) and concerns over vaccine safety (32.0%). Hesitant groups included Christians, urban dwellers, opposition political party voters, people with more years of education, females, people who received COVID-19 information from internet sources, and people who expressed uncertainty about COVID-19 misinformation beliefs.
Outdoor long-range transmission of COVID-19 and patient zero
Authors: Rowe B.R. , Mitchell J.B.A. , Canosa A. , Draxler R.
Published: March 2022

Following the outdoor model of risk assessment developed in one of our previous studies, we demonstrate in the present work that long-range transport of infectious aerosols could initiate patient “zero” creation at distances downwind beyond one hundred kilometers. The very low probability of this outdoor transmission can be compensated by high numbers and densities of infected and susceptible people such as it occurs in large cities, respectively in the source and the target.
Acceptance of COVID 19 vaccine among sub-Sahara African (SSA): a comparative study of residents and diaspora dwellers
Authors: Miner Chundung Asabe , Timothy Chikasirimobi G. , Mashige Khathutshelo Percy , Osuagwu Uchechukwu Levi , Envuladu Esther Awazzi , Amiebenomo Onyekachukwu Mary-Anne , Ovenseri-Ogbomo Godwin , Charwe Deborah Donald , Goson Piwuna Christopher , Ekpenyong Bernadine N , Abu Emmanuel Kwasi , Langsi Raymond , Oloruntoba Richard , Ishaya Tanko , Agho Kingsley
Published: March 2022

The COVID-19 vaccines are being rolled out across all the Sub-Saharan Africa (SSA) countries, with countries setting targets for achieving full vaccination rates. The aim of this study was to compare the uptake of, resistance and hesitancy to the COVID-19 vaccine between SSA locally residents and in the diaspora. This was a cross-sectional study conducted using a web and paper-based questionnaire to obtain relevant information on COVID-19 vaccine acceptance. The survey items included questions on demography, uptake and planned acceptance or non-acceptance of the COVID-19 vaccines among SSAs. Multinomial logistic regression was used to determine probabilities of outcomes for factors associated with COVID-19 vaccination resistance and hesitancy among SSA respondents residing within and outside Africa. Uptake of COVID-19 vaccines varied among the local (14.2%) and diaspora (25.3%) residents. There was more resistance to COVID-19 vaccine among locals (68.1%) and across the sociodemographic variables of sex [ adjusted Relative Risk (ARR) =0.73, 95% CI; 0.58 – 0.93], primary/less [ARR =0.22, 95% CI; 0.12 – 0.40] and bachelor’s degree [ARR =0.58, 95% CI; 0.43 – 0.77] educational levels, occupation [ARR =0.32, 95% CI; 0.25 - 0.40] and working status [ARR =1.40, 95%CI; 1.06 - 1.84]. COVID-19 vaccine hesitancy was almost similar between locals and diasporas (17.7% and 17.8% respectively) significant only among healthcare workers [ARR =0.46, 95% CI; 0.16 – 1.35] in the diaspora after adjusting for the variables. Similarly, knowledge and perception of COVID-19 vaccine among locals were substantial, but only perception was remarkable to resistance [ARR =0.86, 95% CI; 0.82 – 0.90] and hesitancy [ARR =0.85, 95% CI; 0.80 – 0.90] of the vaccine. Differences exist in the factors that influence COVID-19 vaccine acceptance between local SSA residents and those in the diaspora. Knowledge about COVID-19 vaccines affects the uptake, resistance, and hesitancy to the COVID-19 vaccine. Information campaigns focusing on the efficacy and safety of vaccines could lead to improved acceptance of COVID-19 vaccines.
Monoclonal antibody and antiviral therapy for treatment of mild-to-moderate COVID-19 in pediatric patients
Authors: Vora Surabhi B. , Englund Janet A. , Trehan Indi , Waghmare Alpana , Kong Ada , Adler Amanda , Zerr Danielle M.
Published: March 2022

The recent surge of SARS-CoV-2 Omicron variant (B.1.1.529) coincided with new treatment options for mild-to-moderate Covid-19 in high-risk adolescents and adults. In this report we describe patient characteristics, treatment-related process measures and outcomes associated with early Covid-19 therapy in high-risk pediatric patients.
Mobility was a Significant Determinant of Reported COVID-19 Incidence During the Omicron Surge in the Most Populous U.S. Counties
Authors: Harris Jeffrey E.
Published: March 2022

Background

Significant immune escape by the Omicron variant, along with the emergence of widespread worry fatigue, have called into question the robustness of the previously observed relation between population mobility and COVID-19 incidence.

Methods

We employed principal component analysis to construct a one-dimensional summary indicator of six Google mobility categories. We related this mobility indicator to case incidence among 111 of the most populous U.S. counties during the Omicron surge from December 2021 through February 2022.

Results

Reported COVID-19 incidence peaked earlier and declined more rapidly among those counties exhibiting more extensive decline in mobility between December 20 and January 3. Based upon a fixed-effects, longitudinal cohort model, we estimated that every 1-percent decline in mobility between December 20 and January 3 was associated with a 0.63 percent decline in peak incidence during the week ending January 17 (95% confidence interval, 0.40-0.86 percent). Based upon a cross-sectional analysis including mean household size and vaccination participation as covariates, we estimated that the same 1-percent decline in mobility was associated with a 0.36 percent decline in cumulative reported COVID-19 incidence from January 10 through February 28 (95% CI, 0.18-0.54 percent).

Conclusion

Omicron did not simply sweep through the U.S. population until it ran out of susceptible individuals to infect. To the contrary, a significant fraction managed to avoid infection by engaging in risk-mitigating behaviors. More broadly, the behavioral response to perceived risk should be viewed as an intrinsic component of the natural course of epidemics in humans.
IRON REGULATORY PROTEIN (IRP)-MEDIATED IRON HOMEOSTASIS IS CRITICAL FOR NEUTROPHIL DEVELOPMENT AND DIFFERENTIATION IN THE BONE MARROW
Authors: Bonadonna Michael , Altamura Sandro , Tybl Elisabeth , Palais Gael , Qatato Maria , Polycarpou-Schwarz Maria , Schneider Martin , Kalk Christina , Rüdiger Wibke , Ertl Alina , Anstee Natasha , Bogeska Ruzhica , Helm Dominic , Milsom Michael D. , Galy Bruno
Published: March 2022

Iron is mostly devoted to the hemoglobinization of erythrocytes for oxygen transport. Yet, emerging evidence points to a broader role for the metal in hematopoiesis, including the formation of the immune system. Iron availability in mammalian cells is controlled by iron-regulatory proteins (IRP)-1 and −2. We report that global disruption of both IRP1 and IRP2 in adult mice impairs neutrophil development and differentiation in the bone marrow, yielding immature neutrophils with abnormally high glycolytic and autophagic activity, resulting in neutropenia. IRPs promote neutrophil differentiation in a cell intrinsic manner by securing cellular iron supply together with transcriptional control of neutropoiesis to facilitate differentiation to fully mature neutrophils. Unlike neutrophils, monocyte count was not affected by IRP and iron deficiency, suggesting a lineage-specific effect of iron on myeloid output. This study unveils the previously unrecognized importance of IRPs and iron metabolism in the formation of a major branch of the innate immune system.
Thermoregulatory Dynamics Reveal Sex-Specific Inflammatory Responses to Experimental Autoimmune Encephalomyelitis in Mice: Implications for Multiple Sclerosis-Induced Fatigue in Females
Authors: Faraji Jamshid , Bettenson Dennis , Babatunde Stella , Gangur-Powell Tabitha , Yong Voon Wee , Metz Gerlinde A.S.
Published: March 2022

The course of multiple sclerosis (MS) is characterized by striking sex differences in symptoms such as fatigue and impaired thermal regulation, which are associated with aggravated systemic pro-inflammatory processes. The purpose of this study was to replicate these symptoms in experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice in the quest to advance the preclinical study of non-motor symptoms of MS. Male and female C57BL/6 mice exposed to a mild form of EAE were evaluated for the progression of clinical, behavioural, thermal, and inflammatory processes. We show higher susceptibility in females to EAE than males based on greater clinical score and cumulative disease index (CDI), fatigue-like and anxiety-like behaviours. Accordingly, infrared (IR) thermography indicated higher cutaneous temperature in females from post-induction days 12 to 23. Females also responded to EAE with greater splenic and adrenal gland weights than males as well as sex-specific changes in pro- and anti-inflammatory cytokines. These findings provide the first evidence of a sex-specific thermal response to immune-mediated demyelination, thus proposing a non-invasive assessment approach of the psychophysiological dynamics in EAE mice. The results are discussed in relation to the thermoregulatory correlates of fatigue and how endogenously elevated body temperature without direct heat exposure may be linked to psychomotor inhibition in patients with MS.
Observation of topological action potentials in engineered tissues
Authors: Ori Hillel , Ramirez Marc Duque , Hayward Rebecca Frank , Tian He , Ortiz Gloria , Cohen Adam E.
Published: March 2022

Due to the nonlinear current-voltage relations of ion channels, an interface between two tissues can have very different bioelectrical properties compared to either tissue on its own. Here we show experimentally that gap junction-coupled interfaces between non-excitable tissues can be electrically excitable. This topologically protected excitability occurs over a far larger range of ion channel expression levels than does excitability in the bulk. Topological excitations at tissue interfaces can cause local elevations in calcium concentration, possibly providing a bioelectrical mechanism for interface sensing. As in condensed matter physics, topological excitations in electrophysiology constitute a distinct class of phenomena which may show exotic and novel properties.
Patterns of retrieval-related cortico-striatal connectivity are stable across the adult lifespan
Authors: Hill Paul F. , de Chastelaine Marianne , Rugg Michael D.
Published: March 2022

Memory retrieval effects in the striatum are well documented and robust across a number of experimental paradigms and stimulus materials. However, the functional significance of these effects, and whether they are moderated by age, remains unclear. In the present study, we used fMRI paired with an associative recognition task to examine retrieval effects in the striatum in a large sample of healthy young, middle aged, and older adults. We identified anatomically segregated patterns of enhanced striatal BOLD activity during recollection- and familiarity-based memory judgments. Successful recollection was associated with enhanced BOLD activity in bilateral putamen and nucleus accumbens. Familiarity effects were evident in the head of the caudate nucleus bilaterally. Crucially, none of these effects were reliably moderated by age. Using psychophysiological interaction analyses, we observed a monitoring-related increase in functional connectivity between the caudate and regions of the frontoparietal control network, and between the putamen and bilateral retrosplenial cortex and intraparietal sulcus. In all instances, monitoring-related increases in cortico-striatal connectivity were unmoderated by age. These results suggest that the striatum, and the caudate in particular, couples with the frontoparietal control network to support top-down retrieval monitoring operations, and that the integrity of these effects are preserved in advanced age.
VEGFR3 modulates brain microvessel branching in a mouse model of 22q11.2 deletion syndrome
Authors: Cioffi Sara , Flore Gemma , Martucciello Stefania , Bilio Marchesa , Turturo Maria Giuseppina , Illingworth Elizabeth
Published: March 2022

The loss of a single copy of TBX1 accounts for most of the clinical signs and symptoms of 22q11.2 deletion syndrome (22q11.2DS), a common genetic disorder that is characterized by multiple congenital anomalies and brain-related clinical problems, some of which likely have vascular origins. Tbx1 mutant mice have brain vascular anomalies, thus making them a useful model to gain insights into the brain disorders associated with the human disease. Here, we found that Tbx1 has a dynamic expression pattern in brain endothelial cells (ECs), including tip cells, during early vascularization, but it is not expressed in EC progenitors. Its main morphogenetic function in the brain is to regulate negatively filopodia biogenesis and vessel branching. Because of similar phenotypes reported for Vegfr3 loss of function, we pursued a mouse genetic approach to test TBX1-VEGFR3 interaction through gain and loss of function experiments. Vegfr3 is expressed in brain ECs with extensive overlap with Tbx1 expression. We demonstrate that inactivating Vegfr3 in the Tbx1 expression domain in a Tbx1 mutant background enhances vessel branching and filopodia formation to a greater extent than that observed in the individual mutants. Furthermore, using a mouse transgenic line, we show that increasing Vegfr3 expression in the Tbx1 expression domain fully rescued the vessel branching and filopodia phenotypes caused by Tbx1 loss of function. Similar results were obtained using an in vitro model of endothelial tubulogenesis. Overall, these results provide genetic evidence that Vegfr3 is a regulator of early vessel branching and filopodia formation in the brain, and is a likely critical effector of the brain vascular phenotype caused by Tbx1 loss of function.
Geometry of spiking patterns in early visual cortex: a Topological Data Analytic approach
Authors: Guidolin Andrea , Desroches Mathieu , Victor Jonathan D. , Purpura Keith P. , Rodrigues Serafim
Published: March 2022

In the brain, spiking patterns live in a high-dimensional space of neurons and time. Thus, determining the intrinsic structure of this space presents a theoretical and experimental challenge. To address this challenge, we introduce a new framework for applying topological data analysis (TDA) to spike train data and use it to determine the geometry of spiking patterns in the visual cortex. Key to our approach is a parameterized family of distances based on the timing of spikes that quantifies the dissimilarity between neuronal responses. We applied TDA to visually driven single-unit and multiple single-unit spiking activity in macaque V1 and V2. TDA across timescales reveals a common geometry for spiking patterns in V1 and V2 which, among simple models, is most similar to that of a low-dimensional space endowed with Euclidean or hyperbolic geometry with modest curvature. Remarkably, the inferred geometry depends on timescale, and is clearest for the timescales that are important for encoding contrast, orientation, and spatial correlations.
Higher visual areas act like domain-general filters with strong selectivity and functional specialization
Authors: Khosla Meenakshi , Wehbe Leila
Published: March 2022

Neuroscientific studies rely heavily on a-priori hypotheses, which can bias results toward existing theories. Here, we use a hypothesis-neutral approach to study category selectivity in higher visual cortex. Using only stimulus images and their associated fMRI activity, we constrain randomly initialized neural networks to predict voxel activity. Despite no category-level supervision, the units in the trained networks act as detectors for semantic concepts like ‘faces’ or ‘words’, providing solid empirical support for categorical selectivity. Importantly, this selectivity is maintained when training the networks without images that contain the preferred category, strongly suggesting that selectivity is not domain-specific machinery, but sensitivity to generic patterns that characterize preferred categories. The ability of the models’ representations to transfer to perceptual tasks further reveals the functional role of their selective responses. Finally, our models show selectivity only for a limited number of categories, all previously identified, suggesting that the essential categories are already known.

Teaser

Models trained solely to predict fMRI activity from images reveal strong category selectivity in higher visual areas, even without exposure to these categories in training.
Minicollagens play the governing role in polar capsule formation in parasitic cnidarians, the Myxozoa
Authors: Kyslík Jiří , Vancová Marie , Bartošová-Sojková Pavla , Lövy Alena , Holzer Astrid S. , Fiala Ivan
Published: March 2022

Minicollagens are major structural components in the biogenesis of nematocysts in Cnidaria. Sequence mining and recent proteomic analysis of polar capsules, homologues of cnidarian nematocysts, have confirmed the presence of minicollagens in this evolutionarily ancient cnidarian endoparasitic group. Nonetheless, the role of nematocyst-associated proteins in polar capsule morphogenesis has never been studied in myxozoans. Here, we report the gene expression of three myxozoan minicollagens, ncol-1, ncol-3, and the recently identified ncol-5, during the intrapiscine development of Myxidium lieberkuehni, the myxozoan parasite of Northern pike Esox lucius. Moreover, we determined the abundance and localisation of Ncol-1 and Ncol-5 proteins in the developing myxozoan stages by western blotting and by immunofluorescence and immunogold electron microscopy. We found that expression of minicollagens was spatiotemporally restricted to developing polar capsules in sporogonic stages. Intriguingly, Ncol-1 and Ncol-5 were localised as major components of the polar capsule wall and polar tubule. These results support the common origin of nematocysts and myxozoan polar capsules. Furthermore, our findings have practical implications for a more accurate identification of developmental stages of myxozoan parasites.