bluuebunny/crossref_metadata_2025 huggingface dataset:
Model reduction by mean-field homogenization in viscoelastic composites. III. Dual theory
Authors: Lahellec Noel , Idiart Martín I. , Suquet Pierre
Published: May 2021

The mean-field homogenization scheme for viscoelastic composites proposed by Lahellec & Suquet (2013
Int. J. Plasticity
42, 1–13 (
doi:10.1016/j.ijplas.2012.09.005
)) is revisited from the standpoint recently adopted in a companion paper (Idiart MI
et al.
2020
Proc. R. Soc. A
20200407 (
doi:10.1098/rspa.2020.0407
)). It is shown that the scheme generates a reduced-order approximation wherein the microscopic kinetics of the composite are described in terms of a finite set of macroscopic forces identified with the phase averages and intraphase covariances of the various microscopic force fields, which can be evaluated by mean-field homogenization techniques. The approximation exhibits a two-potential structure with a convex complementary energy density but a non-convex force potential. The consequential properties of the approximation are exposed and their implications are discussed. The exposition is supplemented by proofs of equivalence between the present scheme and other candidate schemes proposed in the literature for composites with elementary local rheologies of Maxwellian type.
A new perspective on the BO06 trial in osteosarcoma: short- and long-term prognostic value of histologic response and intensified chemotherapy
Authors: Musta Eni , van Geloven Nan , Anninga Jakob , Gelderblom Hans , Fiocco Marta
Published: May 2021

Purpose

Cure rate models accounting for cured and uncured patients, provide additional insights into long and short term survival. We aim to better understand the prognostic value of histologic response and chemotherapy intensification on cure fraction and progression-free survival (PFS) for the uncured patients.

Methods

A logistic model is assumed for the effect of histologic response and intensified chemotherapy on the cure status, while a Cox regression model is estimated only for the uncured patients on PFS. The mixture cure model is used to simultaneously study these two effects.

Results

Histologic response is a strong prognostic factor for the cure status (OR: 3.00 [1.75-5.17]), but it has no clear effect on PFS for the uncured patients (HR: 0.78 [0.53-1.16]). The cure fractions are 55% [46%-63%] and 29% [22%-35%] among patients with good histologic response (GR) and poor responders (PR) respectively. The intensified regimen was associated with higher cure fraction among PR (OR: 1.90 [0.93 – 3.89]), with no evidence of effect for GR (OR: 0.78 [0.38 – 1.59]).

Conclusions

Accounting for cured patients is valuable in distinguishing the covariate effects on cure and PFS. Estimating cure chances based on these prognostic factors is relevant for counseling patients and can affect treatment decisions.
Evaluation of High Flow Local Extraction on control of the aerosol plume in an operating theatre
Authors: Marriott Logan , Harper Matthew , Zhou Tongming , Sun Chenlin
Published: May 2021

Background

Engineering controls are a necessity for minimising aerosol transmission of SARS-CoV-2, yet so far, little attention has been given to such interventions. High flow local extraction (HFLE) is a standard in other industries that deal with airborne contaminants.

Objective

This study aims to provide a quantitative evaluation of an HFLE concept feasible to implement in most real clinical settings.

Design

A unique combined experimental model of Laser sheet illumination videography paired with continuous nanoparticle counts was used to quantitatively assess the impact of HFLE in an operating theatre. Propylene Glycol was aerosolised via a customised physiological lung simulator and dispersion was measured in 3 dimensions. Cumulative probability heat maps were generated to describe aerosol behaviour. Continuous particle counts were made at 15 locations throughout the room to validate laser assessments.

Results

High flow local extraction reduced dispersion of simulated exhaled aerosols to undetectable levels. With the HFLE in operation and optimally positioned, the aerosol plume was tightly controlled. Particle counts remained at baseline when HFLE was active. HFLE becomes less effective when positioned at increasing distance from the mouth.

Aerosol plume behaviour in the absence of HFLE was highly variable and unpredictable.

Conclusions

This analysis demonstrates great potential for HFLE to have a significant impact in reducing aerosol transmission. Simple HFLE devices can be easily engineered and could be widely deployed without impacting on the safe delivery of care.
A Cross-Sectional Analysis of Oral Health Spending Over the Lifespan in Commercial and Medicaid Insured Populations
Authors: Tranby Eric P , Frantsve-Hawley Julie , Minter-Jordan Myechia , Thommes James , Jacob Matt , Monopoli Michael , Okunev Ilya , Boynes Sean G.
Published: May 2021

Background

Life course theory creates a better framework to understand how oral health needs and challenges align with specific phases of the lifespan, care models, social programs, and changes in policy.

Methods

Data are from the 2018 IBM Watson Multi-State Medicaid Marketscan Database (31 million claims) and the 2018 IBM Watson Dental Commercial and Medicare Supplemental Claims Database (45 million claims). Analysis compares per enrollee spending fee-for-service dental claims and medical spending on dental care from ages 0 to 89.

Results

Dental utilization and spending are lower during the first 4 years of life and in young adulthood than in other periods of life. Stark differences in the timing, impact, and severity of caries, periodontal disease, and oral cancer are seen between those enrolled in Medicaid and commercial dental plans. Early childhood caries and oral cancer occur more frequently and at younger ages in Medicaid populations.

Conclusions

This unique lifespan analysis of the U.S. multi-payer dental care system demonstrates the complexities of the current dental service environment and a lack of equitable access to oral healthcare.

Practical Implications

Health policies should be focused on optimizing care delivery to provide effective preventive care at specific stages of the lifespan.
Prognostic accuracy of shock index for severe postpartum hemorrhage in high-income country: Protocol for a systematic review and meta-analysis
Authors: Makino Yuto , Miyake Kentaro , Okada Asami , Ikeda Yumie , Okada Yohei
Published: May 2021

Background

This review aims to conduct a systematic review and meta-analysis to assess the prognostic value of shock index for prediction of severe Postpartum hemorrhage (PPH) in high-income countries.

Method

We will perform a systematic review and meta-analysis for diagnostic test accuracy (DTA). We will search CENTRAL, MEDLINE (Ovid), Web of Science, and other sources and include all relevant reports on the prognostic accuracy of shock index for severe PPH. The target condition is defined as severe PPH required higher-level care. Two review authors will independently screen the study eligibility and extract data from included studies. Two authors will also assess study quality using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. We will use the hierarchical models comprising both the bivariate model and the hierarchical summary receiver operating characteristic (HSROC) model for data synthesis if appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs).

Trial registration

This review is submitted with University hospital medical information network clinical trial registry (UMIN-CTR) [UMIN 000044230].

Conflicts of interest

All authors declare to have no conflicts of interest

Funding

None
Amplitude setting and dopamine response of finger tapping and gait are related in Parkinson’s disease
Authors: Syeda Hafsa Bareen , Glover Aliyah , Pillai Lakshmi , Kemp Aaron S. , Spencer Horace , Lotia Mitesh , Larson-Prior Linda , Virmani Tuhin
Published: May 2021

Objective

Movement amplitude setting is affected early in Parkinson’s disease (PD), clinically manifesting as bradykinesia. Our objective was to determine if amplitude setting of upper limb bimanual movements and bipedal gait are similarly modulated in PD.

Methods

27 PD and 24 control participants were enrolled. Participants performed a bimanual anti-phase finger tapping task wearing gloves with joint angular sensors, and an instrumented gait assessment. Motor load was varied by asking participants to perform movements at a normal and fast pace. PD participants were evaluated OFF (PD-OFF) and ON (PD-ON) levodopa.

Results

PD-OFF participants had shorter tap interval, smaller tap amplitude, and greater tap amplitude variability than controls in the more affected hands (all p<0.05). Tap amplitude and stride length (p=0.030), and tap frequency and gait cadence (p=0.011) were correlated in PD-OFF. Tap frequency and amplitude were also correlated with motor UPDRS (p<0.005) and bradykinesia motor (p<0.05) and ADL (p<0.005) UPDRS subscales. Levodopa improved mean tap amplitude and stride length during fast tapping in PD participants.

Conclusion

In PD-OFF, mean finger tapping amplitude and gait stride length were correlated and showed similar dopaminergic response.

Significance

Future studies manipulating upper limb amplitude could help provide greater understanding of the networks responsible for amplitude setting in PD.
Epidemiology and genetic diversity of SARS-CoV-2 lineages circulating in Africa
Authors: Okoh Olayinka Sunday , Nii-Trebi Nicholas Israel , Jakkari Abdulrokeeb , Olaniran Tosin Titus , Senbadejo Tosin Yetunde , Kafintu-kwashie Anna Aba , Dairo Emmanuel Oluwatobi , Ganiyu Tajudeen Oladunni , Akaninyene Ifiokakaninyene Ekpo , Ezediuno Louis Odinakaose , Adeosun Idowu Jesulayomi , Ockiya Michael Asebake , Jimah Esther Moradeyo , Spiro David J. , Oladipo Elijah Kolawole , Trovão Nídia S.
Published: May 2021

COVID-19 disease dynamics have been widely studied in different settings around the globe, but little is known about these patterns in the African continent.

To investigate the epidemiology and genetic diversity of SARS-CoV-2 lineages circulating in Africa, more than 2400 complete genomes from 33 African countries were retrieved from the GISAID database and analyzed. We investigated their diversity using various clade and lineage nomenclature systems, reconstructed their evolutionary divergence and history using maximum likelihood inference methods, and studied the case and death trends in the continent. We also examined potential repeat patterns and motifs across the sequences.

In this study, we show that after almost one year of the COVID-19 pandemic, only 143 out of the 782 Pango lineages found worldwide circulated in Africa, with five different lineages dominating in distinct periods of the pandemic. Analysis of the number of reported deaths in Africa also revealed large heterogeneity across the continent. Phylogenetic analysis revealed that African viruses cluster closely with those from all continents but more notably with viruses from Europe. However, the extent of viral diversity observed among African genomes is closest to that of the Oceania outbreak, most likely due to genomic under-surveillance in Africa. We also identified two motifs that could function as integrin-binding sites and N-glycosylation domains.

These results shed light on the evolutionary dynamics of the circulating viral strains in Africa, elucidate the functions of protein motifs present in the genome sequences, and emphasize the need to expand genomic surveillance efforts in the continent to better understand the molecular, evolutionary, epidemiological, and spatiotemporal dynamics of the COVID-19 pandemic in Africa.
Economic Impact Payment, Human Mobility and the COVID-19 Mitigation in the United States
Authors: Zhang Ruohao
Published: May 2021

This paper studies the relationship between the individual’s income and COVID-19 mitigation effort contribution. The paper suggests that in addition to the government mandatory policies, the income compensation policy is an alternative government instrument that helps increase the individual and social aggregate COVID-19 mitigation effort. I empirically test the effect of the income compensation policy by utilizing the United States economic impact payment (EIP) in April 2020 as a quasi-natural experiment, and use the cellphone GPS measured human mobility data as the outcome indicator of the COVID-19 mitigation effort. I find that by receiving EIP, individuals on average significantly increase median home dwell time by 3% – 5% (about 26–45 minutes). This paper highlights an unintended effect of EIP: in addition to providing economic assistance, EIP also helps mitigate the COVID-19 virus transmission.

JEL codes

D11 D12 H41 I12 I14 I18
Socioeconomic Status and COVID-19 Related Outcomes in India: Hospital Based Study
Authors: Sharma Arvind Kumar , Gupta Rajeev , Baig Vaseem Naheed , Singh Teja Veer , Chakraborty Surabhi , Sunda Jagdish P , Dhakar Prahalad , Sharma Shiv P , Panwar Raja Babu , Katoch Vishwa Mohan
Published: May 2021

Background & Objective

COVID-19 infection has disproportionately affected ethnic minorities and deprived populations in Europe and North America. Influence of socioeconomic status on COVID-19 related outcomes has not been studied in India. To determine association of educational status, as marker of socioeconomic status, with COVID-19 related outcomes we performed a study.

Methods

Clinically and virologically confirmed successive patients of COVID-19 presenting at a government hospital in India were recruited. Demographic and clinical details were recorded. The cohort was classified according to educational status into Group 1-illiterate or < primary, Group 2-higher secondary, and Group 3-some college. To compare outcomes among groups we performed univariate and multivariate logistic regression and odds ratios (OR) and 95% confidence intervals (CI) were calculated.

Results

From March-September 2020 we recruited 4645 patients (men 3386, women 1259) with laboratory confirmed COVID-19. Mean age was 46+18y, most lived in moderate or large households and 30.5% had low educational status. Smoking or tobacco use was in 29.5%, co-morbidities in 28.6% and low oxygen concentration (SpO2<95%) at admission in 30%. Average length of hospital stay was 6.8+3.7 days, supplemental oxygen was provided in 18.4%, high flow oxygen or non-invasive ventilation 7.1%, and mechanical ventilation in 3.6%. 340 patients (7.3%) died. Group 1 patients were younger, more women, larger households, higher tobacco use and were more hypoxic at admission with lower lymphocyte counts, elevated liver enzymes and greater kidney dysfunction. In Group 1 vs Groups 2 and 3 requirement of oxygen (21.6 vs 16.7 and 17.0%), non-invasive ventilation (8.0 vs 5.9 and 7.1%), invasive ventilation (4.6 vs 3.5 and 3.1%) and deaths (10.0 vs 6.8 and 5.5%) were significantly greater (p<0.05). Compared to Group 3, OR for deaths were significantly higher in Group 1 (1.91, 1.46-2.51) and Group 2 (1.24, 0.93-1.66). Adjustment for age, sex, household size, risk factors and comorbidities led to attenuation in OR in Groups 1 (1.44, 1.07-1.93) and 2 (1.38, 1.02-1.85) that remained with adjustments for clinical and laboratory parameters and oxygen support in Groups 1 (1.38, 0.99-1.93) and 2 (1.52, 1.01-2.11).

Conclusion

Illiterate and less educational (socioeconomic) status patients with COVID-19 in India have significantly greater adverse in-hospital outcomes and mortality. This is related to more severe disease at presentation.
The human hepatocyte TXG-MAPr: WGCNA transcriptomic modules to support mechanism-based risk assessment
Authors: Callegaro Giulia , Kunnen Steven J. , Trairatphisan Panuwat , Grosdidier Solène , Niemeijer Marije , den Hollander Wouter , Guney Emre , Piñero Gonzalez Janet , Furlong Laura , Webster Yue W. , Saez-Rodriguez Julio , Sutherland Jeffrey J. , Mollon Jennifer , Stevens James L. , van de Water Bob
Published: May 2021

Mechanism-based risk assessment is urged to advance and fully permeate into current safety assessment practices, possibly at early phases of drug safety testing. Toxicogenomics is a promising source of comprehensive and mechanisms-revealing data, but analysis tools to interpret mechanisms of toxicity and specific for the testing systems (e.g. hepatocytes) are lacking. In this study we present the TXG-MAPr webtool (available athttps://txg-mapr.eu/WGCNA_PHH/TGGATEs_PHH/), an R-Shiny-based implementation of weighted gene co-expression networks (WGCNA) obtained from the Primary Human Hepatocytes (PHH) TG-GATEs dataset. Gene co-expression networks (modules) were annotated with functional information (pathway enrichment, transcription factor) to reveal their mechanistic interpretation. Several well-known stress response pathways were captured in the modules, are perturbed by specific stressors and show preserved in rat systems (rat primary hepatocytes and ratin vivoliver), highlighting stress responses that translate across species/testing systems. The TXG-MAPr tool was successfully applied to investigate the mechanism of toxicity of TG-GATEs compounds and using external datasets obtained from different hepatocyte cells and microarray platforms. Additionally, we suggest that module responses can be calculated from targeted RNA-seq data therefore imputing biological responses from a limited gene. By analyzing 50 different PHH donors’ responses to a common stressor, tunicamycin, we were able to suggest modules associated with donor’s traits, e.g. pre-existing disease state, therefore connected to donors’ variability. In conclusion, we demonstrated that gene co-expression analysis coupled to an interactive visualization environment, the TXG-MAPr, is a promising approach to achieve mechanistic relevant, cross-species and cross-platform evaluation of toxicogenomic data.
Cortical network structure mediates response to stimulation: an optogenetic study in non-human primates
Authors: Bloch Julien , Greaves-Tunnell Alexander , Shea-Brown Eric , Harchaoui Zaid , Shojaie Ali , Yazdan-Shahmorad Azadeh
Published: May 2021

As aberrant network-level functional connectivity underlies a variety of neural disorders, the ability to induce targeted functional reorganization would be a profound development towards therapies for neural disorders. Brain stimulation has been shown to alter large-scale network-wide functional connectivity, but the mapping from stimulation to the modification is unclear. Here, we leverage advances in neural interfaces, interpretable machine learning, and graph theory to arrive at a model which accurately predicts stimulation-induced network-wide functional reorganization. The model jointly considers the stimulation protocol and the cortical network structure, departing from the standard approach which only considers the stimulation protocol. We validate our approach in the primary sensorimotor cortex of non-human primates using paired optogenetic stimulation through a large-scale optogenetic interface. We observe that the stimulation protocol only predicts a small portion of the induced functional connectivity changes while the network structure predicts much more, indicating that the underlying network is the primary mediator of the response to stimulation. We extract the relationships linking the stimulation and network characteristics to the functional connectivity changes and observe that the mappings diverge over frequency bands and successive stimulations. Finally, we uncover shared processes governing real-time and longer-term effects of stimulation. Our framework represents a paradigm shift for targeted neural stimulation and can be used to interrogate, improve, and develop stimulation-based interventions for neural disorders.

Teaser

Brain stimulation rewires the brain, but the pre-existing network structure of the brain controls the rewiring.
Evaluation of the Family Liaison Officer (FLO) role during the COVID-19 Pandemic
Authors: Hughes Luke , Anderton Lisa , Taylor Rachel M
Published: May 2021

Objectives

During the first wave of COVID-19 heavy restrictions were placed on hospital visitations in the United Kingdom. To support communication between families and patients a central London hospital introduced the role of the Family Liaison Officer. Communication within healthcare settings is often the subject of contention, particularly for patient’s families. During periods of crisis communication can become strained for patients and their families. We aimed to evaluate the rapid implementation of this role to provide guidance if it was required in the future and to explore the potential for this to become a standard role.

Design

Service evaluation

Setting

Single National Health Service hospital in London.

Methods

Semi-structured video interviews with a convenience sample of 12 participants. Data were analysed using Framework Analysis.

Participants

Family Liaison Officers (n=5) and colleagues who experienced working alongside them (n=7).

Results

Key themes were identified from the interviews pertaining to the role, the team, the impact and the future. Two versions of the role emerged though the process based on the Family Liaison Officer’s previous background: Clinical Family Liaison Officers (primarily nurses) and Pastoral Family Liaison Officers (primarily play specialists). Both the Family Liaison Officers and their colleagues agreed that the role had a very positive impact on the wards during this time. Negative aspects of the role, such as a lack of induction, boundaries or clear structure were also discussed.

Conclusion

The Family Liaison Officer was a key role during the pandemic in facilitating communication between patient, clinical team and family. The challenges associated with the role reflect the speed in which it was implemented but it was evident to those in the role and clinicians who the role was supporting that it has potential to help improve hospital communication, and the work of healthcare staff outside of a pandemic.

Strengths and limitations of this study

This was an in-depth evaluation of the Family Liaison Officer role from the perspective of those in the role and the clinical team who they were providing support.

The sample included representation of the different disciplines who worked in the FLO role.

The evaluation only represents the professional perspective and not the experience of the family.
Vaccination against COVID-19 and society’s return to normality in England: a modelling study of impacts of different types of naturally acquired and vaccine induced immunity
Authors: Song Fujian , Bachmann Max O.
Published: May 2021

Objectives

To project impacts of mass vaccination against COVID-19, and investigate possible impacts of different types of naturally acquired and vaccine-induced immunity on future dynamics of SARS-CoV-2 transmission from 2021 to 2029 in England.

Design

Deterministic, discrete-time population dynamic modelling.

Participants

Population in England.

Interventions

mass vaccination programmes.

Outcome measures

daily and cumulative number of deaths from COVID-19.

Results

If vaccine efficacy is ≥ 70%, the vaccine-induced sterilising immunity lasts ≥ 182 days, and the reinfectivity is greatly reduced (by ≥ 40%), mass vaccination programmes can prevent further COVID-19 outbreaks in England. Under such optimistic scenarios, the cumulative number of COVID-19 deaths is estimated to be from 113,000 to 115,000 by the end of 2029 in England. However, under plausible scenarios with lower vaccine efficacy, shorter durability of immunity, and smaller reduction in reinfectivity, repeated vaccination programmes could not prevent further COVID-19 outbreaks.

Conclusions

Under optimistic scenarios, mass immunisation using efficacious vaccines may enable society safely to return to normality. However, under plausible scenarios with low vaccine efficacy and short durability of immunity, COVID-19 could continue to cause recurrent waves of severe morbidity and mortality despite frequent vaccinations. It is crucial to monitor the vaccination effects in the real world, and to better understand characteristics of naturally acquired and vaccine induced immunity against SARS-CoV-2.

ARTICLE SUMMARY

Strengths and limitations of this study

We used a population dynamic model to assess impacts of vaccination programmes on future dynamics of SARS-CoV-2 transmission dynamics, and to explicitly investigate the impacts of different types of immune responses to SARS-CoV-2 infection and vaccines on the COVID-19 epidemic in England.

The model has been verified based on historically observed outcome data in England, and a large number of projection scenarios are explored.

Findings from our study improves the understanding of key immunological parameters relevant to future SARS-CoV-2 transmission dynamics and vaccination strategies.

This is a deterministic simulation model, and uncertainty in estimated parameters may have not been fully accommodated. There remain many uncertainties regarding durability and types of naturally acquired and vaccine-induced immunity.
Evidence for PKD2L1-positive neurons present distant from the central canal in the ventromedial spinal cord and Medulla of the adult mouse
Authors: Jurčić Nina , Michelle Caroline , Trouslard Jérôme , Wanaverbecq Nicolas , Kastner Anne
Published: May 2021

Neurons in contact with the cerebrospinal fluid (CSF) are found around the medullo-spinal central canal (CC) in adult mice. These neurons (CSF-cNs), located within or below the ependymal cell layer known as the stem cell niche, present a characteristic morphology with a dendrite projecting to the CC and ending with a protrusion. They are GABAergic, characterized by an immature neuronal phenotype and selectively express PKD2L1, a channel member of the TRP channel superfamily with properties of sensory receptor.

Using immunohistological techniques in mice, we characterize a new population of PKD2L1 positive cells that is observed around embryonic day 16 (E16), is present distant from the CC in a zone enriched with astrocytes and ependymal fibers of the ventro-medial spinal cord and medulla. With development, their number appears stable although smaller than that of CSF-cNs and they progressively become more distant from the CC with the reorganization of the CC region. These neurons share both functional and phenotypical properties with CSF-cNs, but they appear subdivided in two groups. One, present along the midline, has a bipolar morphology and extend a long dendrite along ependymal fibers and towards the CC. The second group, localized in more ventro-lateral regions, has a multipolar morphology and no apparent projection to the CC

Altogether, we describe a novel population of PKD2L1+ neurons distant from the CC but with properties similar to CSF-cNs that might serve to sense modification in the composition of either CSF or interstitial liquid, a function that will need to be confirmed.
Targeting neurons in the tumor microenvironment with bupivacaine nanoparticles reduces breast cancer progression and metastases
Authors: Kaduri Maya , Sela Mor , Kagan Shaked , Poley Maria , Abumanhal-Masarweh Hanan , Mora-Raimundo Patricia , Ouro Alberto , Dahan Nitsan , Shklover Jeny , Shainsky-Roitman Janna , Buganim Yosef , Schroeder Avi
Published: May 2021

Neurons within the tumor microenvironment promote cancer progression, thus their local targeting has potential clinical benefits. We designed PEGylated lipid nanoparticles loaded with a non-opioid analgesic, bupivacaine, to target neurons within breast cancer tumors and suppress nerve-to-cancer crosstalk.In vitro, 100-nm nanoparticles were taken up readily by primary neurons, trafficking from the neuronal body and along the axons. We demonstrate that signaling between triple-negative breast cancer cells (4T1) and neurons involves secretion of cytokines stimulating neurite outgrowth. Reciprocally, neurons stimulated 4T1 proliferation, migration and survival through secretion of neurotransmitters. Bupivacaine curbs neurite growth and signaling with cancer cells, inhibiting cancer-cell viability.In vivo, bupivacaine-loaded nanoparticles administered intravenously, suppressed neurons in orthotopic triple-negative breast cancer tumors, inhibiting tumor growth and metastatic dissemination. Overall, our findings suggest that reducing nerve involvement in tumors is important for treating cancer.
Intrinsic mechanical sensitivity of auditory neurons as a contributor to sound-driven neural activity
Authors: Perez Flores Maria C. , Verschooten Eric , Lee Jeong Han , Kim Hyo Jeong , Joris Philip X. , Yamoah Ebenezer N.
Published: May 2021

Mechanosensation – by which mechanical stimuli are converted into a neuronal signal – is the basis for the sensory systems of hearing, balance, and touch. Mechanosensation is unmatched in speed and its diverse range of sensitivities, reaching its highest temporal limits with the sense of hearing; however, hair cells (HCs) and the auditory nerve (AN) serve as obligatory bottlenecks for sounds to engage the brain. Like other sensory neurons, auditory neurons use the canonical pathway for neurotransmission and millisecond-duration action potentials (APs). How the auditory system utilizes the relatively slow transmission mechanisms to achieve ultrafast speed and high audio-frequency hearing remains an enigma. Here, we address this paradox and report that the AN is mechanically sensitive, and minute mechanical displacement profoundly affects its response properties. Sound-mimicking sinusoidal mechanical and electrical current stimuli affect phase-locked responses. In a phase-dependent manner, the two stimuli can also evoke suppressive responses. We propose that mechanical sensitivity interacts with synaptic responses to shape responses in the AN, including frequency tuning and temporal phase-locking. The combination of neurotransmission and mechanical sensation to control spike patterns gives the AN a secondary receptor role, an emerging theme in primary neuronal functions.
Dependable Algorithm for Visualizing Snoring Duration through Acoustic Analysis
Authors: Kao Hsueh-Hsin , Lin Yen-Chang , Kao Yee-Hsin , Ho Madan , Yu Hsiao-Chen , Wang Chun-Lung , Chiang Jui-Kun
Published: May 2021

Background

Snoring is a nuisance for the bed partners of people who snore and is also associated with chronic diseases. Estimating the snoring duration from a whole-night-sleep period is challenging. The authors present a dependable algorithm for visualizing snoring durations through acoustic analysis.

Method

Both instruments (Sony digital recorder and smartphone’s SnoreClock app) were placed within 30 cm from the examinee’s head during the sleep period. Subsequently, spectrograms were plotted based on audio files recorded from Sony recorders. The authors developed an algorithm to validate snoring durations through visualization of typical snoring segments.

Results

In total, 37 snoring recordings obtained from six individuals were analyzed. The mean age of the participants was 44.6 ± 9.9 years. A 3-s segment demonstrated the typical dominant frequency bands and amplitude waves of two snores. Every recorded file was tailored to a regular 600-s segment and plotted. Visualization revealed that the typical features of the clustered snores in the amplitude domains were near-isometric spikes (most had an ascending–descending trend). The recorded snores exhibited one or more visibly fixed frequency bands. Intervals were noted between the snoring clusters and were incorporated into the whole-night snoring calculation. The correlative coefficients of snoring rates of digitally recorded files examined by Examiners A and B were higher (0.865,p< 0.001) than those with SnoreClock app (0.757,p< 0.001; 0.787,p< 0.001, respectively).

Conclusion

A dependable algorithm with high reproducibility was developed for visualizing snoring durations.
Identifiability analysis for models of the translation kinetics after mRNA transfection
Authors: Pieschner Susanne , Hasenauer Jan , Fuchs Christiane
Published: May 2021

Mechanistic models are a powerful tool to gain insights into biological processes. The parameters of such models, e.g. kinetic rate constants, usually cannot be measured directly but need to be inferred from experimental data. In this article, we study dynamical models of the translation kinetics after mRNA transfection and analyze their parameter identifiability. Previous studies have considered ordinary differential equation (ODE) models of the process, and here we formulate a stochastic differential equation (SDE) model. For both model types, we consider structural identifiability based on the model equations and practical identifiability based on simulated as well as experimental data and find that the SDE model provides better parameter identifiability than the ODE model. Moreover, our analysis shows that even for those parameters of the ODE model that are considered to be identifiable, the obtained estimates are sometimes unreliable. Overall, our study clearly demonstrates the relevance of considering different modeling approaches and that stochastic models can provide more reliable and informative results.
Peripheral neuropathy linked mRNA export factor GANP reshapes gene regulation in human motor neurons
Authors: Woldegebriel Rosa , Kvist Jouni , White Matthew , Sinkko Matilda , Hänninen Satu , Sainio Markus T , Torregrosa-Munumer Rubén , Harjuhaahto Sandra , Huber Nadine , Herukka Sanna-Kaisa , Haapasalo Annakaisa , Carpen Olli , Bassett Andrew , Ylikallio Emil , Sreedharan Jemeen , Tyynismaa Henna
Published: May 2021

Loss-of-function of the mRNA export protein GANP (MCM3AP gene) cause early-onset sensorimotor neuropathy, characterised by axonal degeneration in long peripheral nerves. GANP functions as a scaffold at nuclear pore complexes, contributing to selective nuclear export of mRNAs. Here, we aimed to identify motor neuron specific transcripts that are regulated by GANP and may be limiting for local protein synthesis in motor neuron axons. We compared motor neurons with a gene edited mutation in the Sac3 mRNA binding domain of GANP to isogenic controls. We also examined patient-derived motor neurons. RNA sequencing of motor neurons as well as nuclear and axonal subcompartments showed that mutant GANP had a profound effect on motor neuron transcriptomes, with alterations in nearly 40 percent of all expressed genes and broad changes in splicing. Expression changes in multiple genes critical for neuronal functions, combined with compensatory upregulation of protein synthesis and early-stage metabolic stress genes, indicated that RNA metabolism was abnormal in GANP-deficient motor neurons. Surprisingly, limited evidence was found for large-scale nuclear retention of mRNA. This first study of neuropathy-linked GANP defects in human motor neurons shows that GANP has a wide gene regulatory role in a disease-relevant cell type that requires long-distance mRNA transport.
A transcriptomics-guided drug target discovery strategy identifies novel receptor ligands for lung regeneration
Authors: Wu Xinhui , Bos I. Sophie T. , Conlon Thomas M. , Ansari Meshal , Verschut Vicky , Verkleij Lars A. , D’Ambrosi Angela , Matveyenko Aleksey , Schiller Herbert B. , Königshoff Melanie , Schmidt Martina , Kistemaker Loes E. M. , Yildirim Ali Önder , Gosens Reinoud
Published: May 2021

Currently, there is no pharmacological treatment targeting defective tissue repair in chronic disease. Here we utilized a transcriptomics-guided drug target discovery strategy using gene signatures of smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke, identifying druggable targets expressed in alveolar epithelial progenitors of which we screened the function in lung organoids. We found several drug targets with regenerative potential of which EP and IP prostanoid receptor ligands had the most significant therapeutic potential in restoring cigarette smoke-induced defects in alveolar epithelial progenitors in vitro and in vivo. Mechanistically, we discovered by using scRNA-sequencing analysis that circadian clock and cell cycle/apoptosis signaling pathways were enriched in alveolar epithelial progenitor cells in COPD patients and in a relevant model of COPD, which was prevented by PGE2 or PGI2 mimetics. Conclusively, specific targeting of EP and IP receptors offers therapeutic potential for injury to repair in COPD.
Automated Assignment of Proteoform Classification Levels
Authors: Rolfs Zach , Smith Lloyd M.
Published: May 2021

Proteoform identification is required to fully understand the biological diversity present in a sample. However, these identifications are often ambiguous because of the challenges in analyzing full length proteins by mass spectrometry. A five-level proteoform classification system was recently developed to delineate the ambiguity of proteoform identifications and to allow for comparisons across software platforms and acquisition methods. Widespread adoption of this system requires software tools to provide classification of the proteoform identifications. We describe here implementation of the five-level classification system in the software program MetaMorpheus, which provides both bottom-up and top-down identifications. Additionally, we developed a stand-alone program called ProteoformClassifier that allows users to classify proteoform results from any search program, provided that the program writes output that includes the information necessary to evaluate proteoform ambiguity. This stand-alone program includes a small test file and database to evaluate if a given program provides sufficient information to evaluate ambiguity. If the program does not, then ProteoformClassifier provides meaningful feedback to assist developers with implementing the classification system. We tested currently available top-down software programs and found that none of them other than MetaMorpheus provided sufficient information regarding identification ambiguity to permit classification.
Encoding of inflammatory hyperalgesia in mice spinal cord
Authors: Barkai Omer , Butterman Rachely , Rayi Prudhvi Raj , Katz Ben , Lev Shaya , Binshtok Alexander M
Published: May 2021

Inflammation modifies the input-output properties of peripheral nociceptive neurons, thus leading to hyperalgesia, a condition in which the perception of noxious heat stimuli is altered such that the same stimulus produces enhanced pain. The increased nociceptive output enters the superficial dorsal spinal cord (SDH), which comprises the first CNS network integrating the noxious information. Here we used in vivo calcium imaging and a computational approach to investigate how the SDH network in mice encodes the injury-mediated abnormal input from peripheral nociceptive neurons. We show that the application of noxious heat stimuli to the hind paw in naïve mice before induction of injury affects the activity of 70% of recorded neurons by either increasing or suppressing it. Application of the same noxious heat stimuli to hyperalgesic skin following injury leads to activation of previously non-responded cells and de-suppression of the “suppressed” neurons. We further demonstrate that reduction in synaptic inhibition mimics the response to the noxious stimuli in hyperalgesic conditions. Using a computational model of the SDH network, we predict that the “disinhibitory” effect of hyperalgesic stimuli results from the inflammation-mediated increased afferent input to the SDH network and a decrease in SDH inhibition. Both of these processes synergistically contribute to the injury-mediated increase in SDH output towards higher brain centers.
Contactless recordings of retinal activity using optically pumped magnetometers
Authors: Westner Britta U. , Lubell James I. , Jensen Mads , Hokland Sigbjørn , Dalal Sarang S.
Published: May 2021

Optically pumped magnetometers (OPMs) have been adopted for the recording of brain activity. Without the need to be cooled to cryogenic temperatures, an array of these sensors can be placed more flexibly, which allows for the recording of neuronal structures other than neocortex. Here we use eight OPM sensors to record human retinal activity following flash stimulation. We compare this magnetoretinographic (MRG) activity to the simultaneously recorded electroretinogram of the eight participants. The MRG shows the familiar flash-evoked potentials (a-wave and b-wave) and shares a highly significant amount of information with the electroretinogram recording (both in a simultaneous and separate recording). We conclude that OPM sensors have the potential to become a contactless alternative to fiber electrodes for the recording of retinal activity. Such a contactless solution can benefit both clinical and neuroscientific settings.
A multi-site, multi-participant magnetoencephalography resting-state dataset to study dementia: The BioFIND dataset
Authors: Vaghari Delshad , Bruna Ricardo , Hughes Laura E. , Nesbitt David , Tibon Roni , Rowe James B. , Maestu Fernando , Henson Richard N.
Published: May 2021

Early detection of Alzheimer’s Disease (AD) is vital to reduce the burden of dementia and for developing effective treatments. Neuroimaging can detect early brain changes, such as hippocampal atrophy in Mild Cognitive Impairment (MCI), a prodromal state of AD. However, selecting the most informative imaging features by machine-learning requires many cases. While large publically-available datasets of people with dementia or prodromal disease exist for Magnetic Resonance Imaging (MRI), comparable datasets are missing for Magnetoencephalography (MEG). MEG offers advantages in its millisecond resolution, revealing physiological changes in brain oscillations or connectivity, before structural changes are evident with MRI. We introduce a MEG dataset with 324 individuals: patients with MCI and healthy controls. Their brain activity was recorded while resting with eyes closed, using a 306-channel MEG scanner at one of two sites (Madrid or Cambridge), enabling tests of generalization across sites. A T1-weighted MRI is provided to assist source localisation. The MEG and MRI data can be formatted according to international BIDS standards, and analysed freely on the DPUK platform (https://portal.dementiasplatform.uk/Apply).
Expression and analysis of the SAM-dependent RNA methyltransferase Rsm22 from Saccharomyces cerevisiae
Authors: Alam Jahangir , Rahman Farah Tazkera , Sah-Teli Shiv K. , Venkatesan Rajaram , Koski M. Kristian , Autio Kaija J. , Hiltunen J. Kalervo , Kastaniotis Alexander J.
Published: May 2021

The Saccharomyces cerevisiae Rsm22 protein (Sc-Rsm22), encoded by the nuclear RSM22 (systematic name YKL155c) gene, is a distant homologue of Rsm22 from Trypanosoma brucei (Tb-Rsm22) and METTL17 from mouse (Mm-METTL17). All three proteins have been shown to be associated with mitochondrial gene expression, and Sc-Rsm22 has been documented to be essential for mitochondrial respiration. The Sc-Rsm22 protein comprises a polypeptide of molecular weight 72.2 kDa that is predicted to harbor an N-terminal mitochondrial targeting sequence. The precise physiological function of Rsm22-family proteins is unknown, and no structural information has been available for Sc-Rsm22 to date. In this study, Sc-Rsm22 was expressed and purified in monomeric and dimeric forms, their folding was confirmed by circular-dichroism analyses and their low-resolution structures were determined using a small-angle X-ray scattering (SAXS) approach. The solution structure of the monomeric form of Sc-Rsm22 revealed an elongated three-domain arrangement, which differs from the shape of Tb-Rsm22 in its complex with the mitochondrial small ribosomal subunit in T. brucei (PDB entry 6sg9). A bioinformatic analysis revealed that the core domain in the middle (Leu117–Asp462 in Sc-Rsm22) resembles the corresponding region in Tb-Rsm22, including a Rossmann-like methyltransferase fold followed by a zinc-finger-like structure. The latter structure is not present in this position in other methyltransferases and is therefore a unique structural motif for this family. The first half of the C-terminal domain is likely to form an OB-fold, which is typically found in RNA-binding proteins and is also seen in the Tb-Rsm22 structure. In contrast, the N-terminal domain of Sc-Rsm22 is predicted to be fully α-helical and shares no sequence similarity with other family members. Functional studies demonstrated that the monomeric variant of Sc-Rsm22 methylates mitochondrial tRNAs in vitro. These data suggest that Sc-Rsm22 is a new and unique member of the RNA methyltransferases that is important for mitochondrial protein synthesis.
The resilient – smart city development: a literature review and novel frameworks exploration
Authors: Khatibi Hamed , Wilkinson Suzanne , Baghersad Mostafa , Dianat Heiman , Ramli Hidayati , Suhatril Meldi , Javanmardi Ahad , Ghaedi Khaled
Published: May 2021

Purpose

This paper aims to develop a framework that could establish and further the terminology of smart city/resilient city discourse in that resilience could support urban “smartness”, a term that is widely argued being not easily measured nor quantifiably assessed.

Design/methodology/approach

The qualitative approach was employed, and based on selected keywords, a systematic literature review was carried out to understand the main themes within the smart city and resilient city concepts databases. Upon screening, 86 papers were used and synthesised through the meta-synthesis method using both synthesis approach, meta-aggregation and meta-ethnography that systematically identifies both properties and characteristics, to build an innovative framework as an indicator-based smart/resilience quantification model.

Findings

Two novel frameworks are proposed, smart resilient city (SRC) and resilient smart city (RSC), as guidelines regulatory that establish a city's smartness and resilience.

Research limitations/implications

The quantitative research phase is not provided as the framework builds on the exploratory approach in which the model is proposed through the postulation of data definitions.

Practical implications

Although the study's scope was limited to the city, proposed frameworks may be interpreted for other contexts that deal with the topic of resilience and smart.

Originality/value

The established framework proposal would encourage further exploration in context, serving as an inspiration for other scholars, decision-makers, as well as municipalities to keep strengthening smart city through resilience factors.
Understanding the disclosure of personal data online
Authors: Parker Heather J. , Flowerday Stephen
Published: May 2021

Purpose

Social media has created a new level of interconnected communication. However, the use of online platforms brings about various ways in which a user’s personal data can be put at risk. This study aims to investigate what drives the disclosure of personal information online and whether an increase in awareness of the value of personal information motivates users to safeguard their information.

Design/methodology/approach

Fourteen university students participated in a mixed-methods experiment, where responses to Likert-type scale items were combined with responses to interview questions to provide insight into the cost–benefit analysis users conduct when disclosing information online.

Findings

Overall, the findings indicate that users are able to disregard their concerns due to a resigned and apathetic attitude towards privacy. Furthermore, subjective norms enhanced by fear of missing out (FOMO) further allows users to overlook potential risks to their information in order to avoid social isolation and sanction. Alternatively, an increased awareness of the personal value of information and having experienced a previous privacy violation encourage the protection of information and limited disclosure.

Originality/value

This study provides insight into privacy and information disclosure on social media in South Africa. To the knowledge of the researchers, this is the first study to include a combination of the theory of planned behaviour and the privacy calculus model, together with the antecedent factors of personal valuation of information, trust in the social media provider, FOMO.