bluuebunny/crossref_metadata_2025 huggingface dataset:
Informing antenna design for sky-averaged 21-cm experiments using a simulated Bayesian data analysis pipeline
Authors: Anstey Dominic , Cumner John , de Lera Acedo Eloy , Handley Will
Published: November 2021

Global 21-cm experiments aim to measure the sky-averaged H i absorption signal from cosmic dawn and the epoch of reionization. However, antenna chromaticity coupling to bright foregrounds can introduce distortions into the observational data of such experiments. We demonstrate a method for guiding the antenna design of a global experiment through data analysis simulations. This is done by performing simulated observations for a range of inserted 21-cm signals and then attempting to identify the signals with a data analysis pipeline. We demonstrate this method on five antennas that were considered as potential designs for the Radio Experiment for the Analysis of Cosmic Hydrogen: a conical log spiral antenna, an inverted conical sinuous antenna, and polygonal-, rectangular-, and elliptical-bladed dipoles. We find that the log spiral performs significantly better than the other antennas tested, able to correctly and confidently identify every inserted 21-cm signal. In second place is the polygonal dipole antenna, which was only unable to detect signals with both very low amplitudes of 0.05 K and low centre frequency of 80 MHz. The conical sinuous antenna was found to perform least accurately, only able to detect the highest amplitude 21-cm signals, and even then with biases. We also demonstrate that, due to the non-trivial nature of chromatic distortion and the processes of correcting for it, these are not the results that could have been expected superficially from the extent of chromatic variation in each antenna.
Second-generation dust in planetary systems: the case of HD 163296
Authors: D’Angelo Gennaro , Marzari Francesco
Published: November 2021

Observations indicate that large, dust-laden protoplanetary discs are common. Some features, like gaps, rings, and spirals, suggest they may host young planets, which can excite the orbits of nearby leftover planetesimals. Energetic collisions among these bodies can lead to the production of second-generation dust. Grains produced by collisions may have a dynamical behaviour different from that of first-generation, primordial dust out of which planetesimals and planets formed. We aim to study these differences for the HD 163296 system and determine whether dynamical signatures in the mixture of the two dust populations can help separate their contributions. We use three-dimensional (3D) hydrodynamic models to describe the gaseous disc with three, Saturn- to Jupiter-mass, embedded planets. Dust grains, of sizes $1\, \mu \mathrm{m}$–$1\, \mathrm{mm}$, are treated as Lagrangian particles with resolved thermodynamics and mass-loss. Initial disc and planet configurations are derived from observation-based work, which indicates low gas viscosity. The 3D approach also allows us to detect the formation of vortices induced by Rossby waves, where dust becomes concentrated and may contribute to planetesimal formation. We find that the main differences in the dynamical behaviour of first- and second-generation dust occur in the vertical distribution. The two populations have similar distributions around the disc mid-plane, although second-generation dust shows longer residence times close to the radial locations of the planets’ gas gaps. Sedimentation rates of $\mu$m-sized grains are comparable to or lower than the production rates by planetesimals’ collisions, making this population potentially observable. These outcomes can be extended to similar systems harbouring giant planets.
Charged particles energization during magnetic reconnection in the Earth’s magnetosphere by double layers: an analytical approach
Authors: Shamir M , Khan Imran A , Murtaza G
Published: November 2021

Charged particles energization at the magnetic reconnection sites in the Earth’s magnetosphere is a subject of active debate in space plasma, specifically in magnetopause and magnetotail regions. In the proximity of the reconnection region, Magnetospheric Multiscale (MMS) and other satellite missions have confirmed the existence of electron acceleration ranging from 100 keV to MeV. There is also evidence of cold ions acceleration in the separatrix region of the Earth’s magnetopause. An important candidate responsible for charged particles acceleration is believed to be the double layer (DL) structures, and which were first observed by the Cluster satellite in the separatrix region of the Earth’s magnetosphere. Moreover, the MMS mission also observed parallel electric field fluctuations up to 100 mV/m carried by DL at the magnetic reconnection site in the Earth’s magnetosphere. Motivated by the reported literature, we investigate the DL and its associated electric field at the magnetopause magnetic reconnection site by using a simple analytical model in which the DLs associated with kinetic Alfvén waves are studied in a low- $\beta$ electron-ion plasma with Tsallis distributed electrons and fluid ions using the Sagdeev potential technique. The non-extensive parameter (superthermality) of the Tsallis distribution has a pronounced effect on the DL’s strength (as defined by the potential drop) and its associated parallel electric field. Our results are consistent with the earlier studies on DLs in Earth’s magnetosphere. Additionally, we discuss the implications of our findings on charged particle energization in the separatrix region of the Earth’s magnetopause during magnetic reconnection.
Bottling the champagne: dynamics and radiation trapping of wind-driven bubbles around massive stars
Authors: Geen Sam , de Koter Alex
Published: November 2021

In this paper, we make predictions for the behaviour of wind bubbles around young massive stars using analytic theory. We do this in order to determine why there is a discrepancy between theoretical models that predict that winds should play a secondary role to photoionization in the dynamics of H iiregions, and observations of young H iiregions that seem to suggest a driving role for winds. In particular, regions such as M42 in Orion have neutral hydrogen shells, suggesting that the ionizing radiation is trapped closer to the star. We first derive formulae for wind bubble evolution in non-uniform density fields, focusing on singular isothermal sphere density fields with a power-law index of -2. We find that a classical ‘Weaver’-like expansion velocity becomes constant in such a density distribution. We then calculate the structure of the photoionized shell around such wind bubbles, and determine at what point the mass in the shell cannot absorb all of the ionizing photons emitted by the star, causing an ‘overflow’ of ionizing radiation. We also estimate perturbations from cooling, gravity, magnetic fields and instabilities, all of which we argue are secondary effects for the conditions studied here. Our wind-driven model provides a consistent explanation for the behaviour of M42 to within the errors given by observational studies. We find that in relatively denser molecular cloud environments around single young stellar sources, champagne flows are unlikely until the wind shell breaks up due to turbulence or clumping in the cloud.
Period-change rates in Large Magellanic Cloud Cepheids revisited
Authors: Rodríguez-Segovia N , Hajdu G , Catelan M , Espinoza-Arancibia F , Boggiano G , Cenzano C , Garcés E H , Joachimi K , Muñoz-López C , Ordenes-Huanca C , Orquera-Rojas C , Torres P , Valenzuela-Navarro Á
Published: November 2021

The period-change rate (PCR) of pulsating variable stars is a useful probe of changes in their interior structure, and thus of their evolutionary stages. So far, the PCRs of classical Cepheids in the Large Magellanic Cloud (LMC) have been explored in a limited sample of the total population of these variables. Here, we use a template-based method to build observed-minus-computed (O − C) period diagrams, from which we can derive PCRs for these stars by taking advantage of the long time baseline afforded by the Digital Access to a Sky Century @ Harvard light curves, combined with additional data from the Optical Gravitational Lensing Experiment, the MAssive Compact Halo Object project, Gaia’s Data Release 2, and in some cases the All-Sky Automated Survey. From an initial sample of 2315 sources, our method provides an unprecedented sample of 1303 LMC classical Cepheids with accurate PCRs, the largest for any single galaxy, including the Milky Way. The derived PCRs are largely compatible with theoretically expected values, as computed by our team using the Modules for Experiments in Stellar Astrophysics code, as well as with similar previous computations available in the literature. Additionally, five long-period ($P\,\gt\, 50\, \rm {d}$) sources display a cyclic behaviour in their O − C diagrams, which is clearly incompatible with evolutionary changes. Finally, on the basis of their large positive PCR values, two first-crossing Cepheid candidates are identified.
Inferring the morphology of AGN torus using X-ray spectra: a reliability study
Authors: Saha Tathagata , Markowitz Alex G , Buchner Johannes
Published: November 2021

Numerous X-ray spectral models have been developed to model emission reprocessed by the torus of an active galactic nucleus (AGN), e.g. UXCLUMPY, CTORUS, and MYTORUS. They span a range of assumed torus geometries and morphologies – some posit smooth gas distributions, and others posit distributions of clouds. It is suspected that given the quality of currently available data, certain model parameters, such as coronal power-law photon index and parameters determining the morphology of the AGN torus, may be poorly constrained due to model degeneracies. In this work, we test the reliability of these models in terms of recovery of parameters and the ability to discern the morphology of the torus using XMM–Newton and NuSTAR spectral data. We perform extensive simulations of X-ray spectra of Compton-thick AGNs under six X-ray spectral models of the torus. We use Bayesian methods to investigate degeneracy between model parameters, distinguish models and determine the dependence of the parameter constraints on the instruments used. For typical exposure times and fluxes for nearby Compton-thick AGN, we find that several parameters across the models used here cannot be well constrained, e.g. the distribution of clouds, the number of clouds in the radial direction, even when the applied model is correct. We also find that Bayesian evidence values can robustly distinguish between a correct and a wrong model only if there is sufficient energy coverage and only if the intrinsic flux of the object is above a particular value determined by the instrument combination and the model considered.
Variation in Release Factor Abundance Is Not Needed to Explain Trends in Bacterial Stop Codon Usage
Authors: Ho Alexander T , Hurst Laurence D
Published: November 2021

In bacteria stop codons are recognized by one of two class I release factors (RF1) recognizing TAG, RF2 recognizing TGA, and TAA being recognized by both. Variation across bacteria in the relative abundance of RF1 and RF2 is thus hypothesized to select for different TGA/TAG usage. This has been supported by correlations between TAG:TGA ratios and RF1:RF2 ratios across multiple bacterial species, potentially also explaining why TAG usage is approximately constant despite extensive variation in GC content. It is, however, possible that stop codon trends are determined by other forces and that RF ratios adapt to stop codon usage, rather than vice versa. Here, we determine which direction of the causal arrow is the more parsimonious. Our results support the notion that RF1/RF2 ratios become adapted to stop codon usage as the same trends, notably the anomalous TAG behavior, are seen in contexts where RF1:RF2 ratios cannot be, or are unlikely to be, causative, that is, at 3′untranslated sites never used for translation termination, in intragenomic analyses, and across archaeal species (that possess only one RF1). We conclude that specifics of RF biology are unlikely to fully explain TGA/TAG relative usage. We discuss why the causal relationships for the evolution of synonymous stop codon usage might be different from those affecting synonymous sense codon usage, noting that transitions between TGA and TAG require two-point mutations one of which is likely to be deleterious.
RNA marker modifications reveal the necessity for rigorous preparation protocols to avoid artifacts in epitranscriptomic analysis
Authors: Richter Florian , Plehn Johanna E , Bessler Larissa , Hertler Jasmin , Jörg Marko , Cirzi Cansu , Tuorto Francesca , Friedland Kristina , Helm Mark
Published: November 2021

The accurate definition of an epitranscriptome is endangered by artefacts resulting from RNA degradation after cell death, a ubiquitous yet little investigated process. By tracing RNA marker modifications through tissue preparation protocols, we identified a major blind spot from daily lab routine, that has massive impact on modification analysis in small RNAs. In particular, m6,6A and Am as co-varying rRNA marker modifications, appeared in small RNA fractions following rRNA degradation in vitro and in cellulo. Analysing mouse tissue at different time points post mortem, we tracked the progress of intracellular RNA degradation after cell death, and found it reflected in RNA modification patterns. Differences were dramatic between liver, where RNA degradation commenced immediately after death, and brain, yielding essentially undamaged RNA. RNA integrity correlated with low amounts of co-varying rRNA markers. Thus validated RNA preparations featured differentially modified tRNA populations whose information content allowed a distinction even among the related brain tissues cortex, cerebellum and hippocampus. Inversely, advanced cell death correlated with high rRNA marker content, and correspondingly little with the naïve state of living tissue. Therefore, unless RNA and tissue preparations are executed with utmost care, interpretation of modification patterns in tRNA and small RNA are prone to artefacts.
Voltage-dependent anion channel proteins associate with dynamicBamboo mosaic virus-induced complexes
Authors: Lee Hsiang-Chi , Huang Ying-Ping , Huang Ying-Wen , Hu Chung-Chi , Lee Chin-Wei , Chang Chih-Hao , Lin Na-Sheng , Hsu Yau-Heiu
Published: November 2021

Infection cycles of viruses are highly dependent on membrane-associated host factors. To uncover the infection cycle of Bamboo mosaic virus (BaMV) in detail, we purified the membrane-associated viral complexes from infected Nicotiana benthamiana plants and analyzed the involved host factors. Four isoforms of voltage-dependent anion channel (VDAC) proteins on the outer membrane of mitochondria were identified due to their upregulated expression in the BaMV complex-enriched membranous fraction. Results from loss- and gain-of-function experiments indicated that NbVDAC2, -3, and -4 are essential for efficient BaMV accumulation. During BaMV infection, all NbVDACs concentrated into larger aggregates, which overlapped and trafficked with BaMV virions to the structure designated as the “dynamic BaMV-induced complex.” Besides the endoplasmic reticulum and mitochondria, BaMV replicase and double-stranded RNAs were also found in this complex, suggesting the dynamic BaMV-induced complex is a replication complex. Yeast two-hybrid and pull-down assays confirmed that BaMV triple gene block protein 1 (TGBp1) could interact with NbVDACs. Confocal microscopy revealed that TGBp1 is sufficient to induce NbVDAC aggregates, which suggests that TGBp1 may play a pivotal role in the NbVDAC–virion complex. Collectively, these findings indicate that NbVDACs may associate with the dynamic BaMV-induced complex via TGBp1 and NbVDAC2, -3, or -4 and can promote BaMV accumulation. This study reveals the involvement of mitochondrial proteins in a viral complex and virus infection.
DE-STRESS: a user-friendly web application for the evaluation of protein designs
Authors: Stam Michael J , Wood Christopher W
Published: November 2021

De novo protein design is a rapidly growing field, and there are now many interesting and useful examples of designed proteins in the literature. However, most designs could be classed as failures when characterised in the lab, usually as a result of low expression, misfolding, aggregation or lack of function. This high attrition rate makes protein design unreliable and costly. It is possible that some of these failures could be caught earlier in the design process if it were quick and easy to generate information and a set of high-quality metrics regarding designs, which could be used to make reproducible and data-driven decisions about which designs to characterise experimentally.

We present DE-STRESS (DEsigned STRucture Evaluation ServiceS), a web application for evaluating structural models of designed and engineered proteins. DE-STRESS has been designed to be simple, intuitive to use and responsive. It provides a wealth of information regarding designs, as well as tools to help contextualise the results and formally describe the properties that a design requires to be fit for purpose.
Making university and industry research collaboration: Evidence from co-inventions in Japan
Authors: Nishimura Junichi , Nagaoka Sadao , Akaike Shinichi , Hosono Mitsuaki
Published: November 2021

This paper examines the making of university and industry research collaboration from the perspective of matching theory. Our analysis, based on an original survey in Japan, aims at identifying the mechanism of matching. The major findings are as follows. There is significant evidence for positive assortative matching at the project level: a researcher with better seeds or better needs gives a higher value to the partner’s research capability and the goodness-of-fit between the project and the partner’s capability in selecting its partner. The projects with the partners selected for research capability and goodness-of-fit are associated with high university and industry research collaboration performance. Furthermore, own contact is most used for positive assortative matching. These results indicate the importance of deep field knowledge and tacit knowledge of the researcher in the search process. These findings suggest that technology transfer policy would need to pay significant attention to the contribution of the decentralized matching process.
The Impact of Unplanned Return to the Operating Room on Health-related Quality of Life at the End of Growth-friendly Surgical Treatment for Early-onset Scoliosis
Authors: Roye Benjamin D. , Fano Adam N. , Matsumoto Hiroko , Fields Michael W. , Emans John B. , Sponseller Paul , Smith John T. , Thompson George H. , White Klane K. , Vitale Michael G.
Published: November 2021

Background:

Limiting complications, especially unplanned return to the operating room (UPROR), is a major focus in the surgical management of early-onset scoliosis (EOS). Although UPROR remains common in this population, its effect on long-term health-related quality of life (HRQoL) remains unclear. The purpose of this study was to investigate the association between UPROR and end-of-treatment HRQoL in EOS patients treated with growth-friendly instrumentation.

Methods:

Patients with EOS who underwent growth-friendly instrumentation at age less than 10 years from 1993 to 2018, and completed treatment, were identified in a multicenter EOS registry. UPROR events were recorded, and end-of-treatment (defined as skeletal maturity and/or definitive spinal fusion) HRQoL was assessed via the 24-item Early-Onset Scoliosis Questionnaire (EOSQ-24).

Results:

A total of 825 patients were identified, and 325 patients (age at surgery: 6.4 y, follow-up: 8.1 y) had end-of-treatment HRQoL data necessary for our investigation. Overall, 129/325 (39.7%) patients experienced 264 UPROR events; the majority (54.2%) were implant-related. Aside from age and etiology, no other variables were determined to be confounders or effect modifiers. Congenital patients with UPROR had worse pain/discomfort by 10.4 points (P=0.057) and worse pulmonary function by 7.8 points (P=0.102) compared with non-UPROR patients adjusting for age. Neuromuscular patients with UPROR had worse pulmonary function by 10.1 points compared with non-UPROR patients adjusting for age (P=0.037). Idiopathic and syndromic patients with UPROR reported consistently worse domain scores than their non-UPROR counterparts, but smaller (<5-point) differences were seen.

Conclusions:

UPROR during growth-friendly surgical treatment for EOS is associated with worse HRQoL in all patients, but particularly in those with neuromuscular or congenital etiologies. Ongoing efforts to avoid UPROR are critical.

Level of Evidence:

Level II. This is a multicenter retrospective cohort study investigating the effect of UPROR on HRQoL (prognostic study).
The Impact of the COVID-19 Global Pandemic on Undergraduate Nursing Students' Study of Anatomy and Physiology
Authors: Abdelkader Amany , Barbagallo Michael S.
Published: November 2021

The COVID-19 global pandemic caused major disruptions to the delivery of human Anatomy and Physiology courses to nursing students worldwide. The aim of the current study is to evaluate nursing students' experiences and perceptions of transitioning from a blended to a purely online study mode for first year Anatomy and Physiology courses during the global pandemic. Qualitative and quantitative methodologies were used with a sample of undergraduate nursing students enrolled at a regional Australian university across its three campuses. Descriptive statistical analysis was used to describe the study population. Content analysis was used to evaluate the participants' use of resources, experiences, and preferences in studying anatomy and physiology. There were 101 participants recruited in the study. Results indicated that face-to-face study mode (41.86%) was the preferred method of delivery during the global pandemic and participants were having a renewed appreciation for the blended study mode (38.37%). Online study mode was the least preferred (19.77%), with the participants' opinions of this mode of study not altered by the global pandemic. Although the COVID-19 global pandemic shifted the traditional teaching of anatomy and physiology in nursing programs to an online environment, the long-term impacts of this disruption have yet to be ascertained.
The Associations Between Child-Care Services During the Preschool Years and High School Graduation: A 20-Year Longitudinal Population-Based Study
Authors: Losier Talia , Orri Massimiliano , Boivin Michel , Larose Simon , Japel Christa , Tremblay Richard E. , Côté Sylvana M.
Published: November 2021

Objective:

Together with family factors, early care and education (ECE) services were shown to improve school readiness in kindergarten. However, it is not clear whether better school readiness at age 6 years translates into higher rates of high school graduation years later. Our objective was therefore to investigate the long-term associations between the use of ECE and high school graduation while considering the sex of the child and the socioeconomic status of the parents as moderators.

Methods:

Participants were children from the Quebec Longitudinal Study on Child Development (QLSCD) born in 1997 to 1998 (N = 2001). Intensity and type of ECE exposure were measured from age 5 months to 5 years. Administrative records were used to determine whether students had obtained a high school diploma by age 20 years. Factors explaining differences in the profiles of ECE users were controlled using propensity score weights.

Results:

Twenty-two percent of students did not have a high school diploma by age 20 years. Compared with children never exposed to center-based care, those exposed early (i.e., before toddlerhood) had better odds of graduating from high school (odds ratio = 1.49) after controlling for confounding factors. Late exposure to center-based care was not related to high school graduation rates.

Conclusion:

Exposure to regulated and center-based ECE on a regular basis from toddlerhood to school entry was associated with higher rates of high school graduation. Regulated center-based ECE at the population level may improve rates of high school graduation.
Application of the “Monitoring Child Development in Integrated Management of Childhood Illnesses Context” in Indian Infants and Toddlers
Authors: Mukherjee Sharmila Banerjee , Jain Abhishek , Annadurai Aswini , Sharma Suvasini
Published: November 2021

Objective:

The objective of this study was to determine the diagnostic accuracy of “Monitoring Child Development in the Integrated Management of Childhood Illnesses Context” (MCDIC) for developmental screening of Indian children younger than 3 years.

Method:

A hospital-based study of diagnostic accuracy was conducted over 17 months after obtaining institutional ethics committee approval. Children younger than 3 years were included in this study. Children with acute illnesses and who presented without their primary caregiver were excluded from this study. The calculated sample size was 272. Eligible children were enrolled after informed consent and stratified by age. MCDIC (index tool) was administrated to primary caregivers by trained interviewers to identify “suspected/probable developmental delay (SDD/PDD).” The reference tools included Developmental Profile, Third Edition, which assessed developmental status based on General Developmental Score (GDS), and Vineland Adaptive Behavior Scale, Second Edition, which evaluated adaptive function based on Adaptive Behavior Composite (ABC). Parameters of diagnostic accuracy were computed according to the number of children with “SDD/PDD” and “developmental delay” (GDS and ABC < −2 SDs).

Results:

The number of eligible children was 312. The sensitivity of MCDIC was 88.0% (95% confidence interval [CI] 68.8–97.5), specificity 85.7 (95% CI 81.1–89.6), positive predictive value 34.9 (95% CI 28.0–42.5), and negative predictive value 98.8 (95% CI 96.6–99.6).

Conclusion:

MCDIC had a high sensitivity and specificity that were above 70% and 80%, respectively, and a high negative predictive value, making it a suitable tool for screening and surveillance of Indian children younger than 3 years.
Subjective Responses to Various Filling Solutions in the Posterior Fluid Reservoir of Miniscleral Lenses at Application
Authors: Tan Jacqueline , Peguda Rajini , Siddireddy Jaya Sowjanya , Briggs Nancy , Stapleton Fiona
Published: November 2021

Purpose:

To compare the effect of the use of different lubrication eye drops and nonpreserved saline for the application of miniscleral contact lenses (CLs) on subjective experience during 6 hr of lens wear.

Methods:

Experienced soft CL wearers aged 18 to 45 years (inclusive) were enrolled in this prospective, randomized, double-masked, three arm comparison cross-over study. Subjects were custom fitted with KATT 16.5 mm diameter miniscleral lenses, ordered to their prescription. Subjects attended visits on three separate days and were randomized to receive instillation of an HP-guar/nanoemulsion drop or an HP-guar/sodium hyaluronate (HA) eye drop into the miniscleral lens before filling with saline or filling with saline alone (control). Subjective responses were collected up to 6 hr postapplication. Generalized linear mixed models with multinomial distribution and cumulative logit link were used to compare the rate at which responses improved post-CL application for the different treatments.

Results:

Twenty-four participants completed the study. Dryness symptoms were more likely to improve at a slower rate postlens application with saline alone compared with the addition of HP-guar/nanoemulsion (P=0.005) or HP-guar/HA (P=0.049) before lens application. Furthermore, the addition of HP-guar/nanoemulsion was more effective than saline alone in improving symptoms of fluctuating vision (P=0.011), grittiness/burning/stinging (P=0.001), and foreign body sensation (P=0.006) more quickly.

Conclusions:

The use of postlens lubrication may be useful in enhancing adaptation to miniscleral lenses.
Laryngeal cancers in paediatric and young adult patients: epidemiology, biology and treatment
Authors: Lechien Jerome R. , Sadoughi Babak , Hans Stéphane
Published: November 2021

Purpose of review

The aim of thi study was to review the recent literature on epidemiology, biology and treatment of laryngeal cancer in paediatric and young adult patients.

Recent findings

Epidemiological studies reported that 2–10% of patients with laryngeal cancer are younger than 40-year-old, while the prevalence of laryngeal cancer remains unknown in the paediatric population. The development of laryngeal cancer in young adults is multifactorial and may be linked to common carcinogens (tobacco and alcohol), occupational factors, laryngopharyngeal reflux, immunosuppression, human papillomavirus infection and genetic polymorphism. A substantial number of cohort studies reported a significant lower proportion of drinkers and smokers in young populations with laryngeal cancer, supporting the higher prevalence of chromosomal losses or abnormalities predisposing to cancer in this group. The development of laryngeal cancer in paediatric patients is strongly associated with genetic syndromes with DNA repair abnormalities. The pathological, clinical and survival outcome differences between young and old patient groups vary significantly between studies, depending on epidemiological, genetic features and therapeutic strategies used.

Paediatric and adult populations with laryngeal cancer present different clinical, pathological and survival outcomes. In the adult population, the patient age at the time of disease development underlies genetic and etiological differences with different mutation patterns between young and old patients, the latter being more frequently individuals with a history of tobacco and alcohol abuse. The differences between age groups regarding stage of cancer at initial presentation, as well as clinical and survival outcomes, are unclear, which may be due to demographic, ethnicity and population genetic differences.
Obligations and Behaviors That Impact Sleep in Prelicensure Baccalaureate Nursing Students
Authors: Blome Melissa , Johnson Michelle , Beck Mark , Jones Mark
Published: November 2021

Background

Nursing students have obligations and behaviors that impact sleep.

Purpose

The purpose of this study was to investigate sleep among prelicensure baccalaureate nursing students and describe factors that impact their sleep quality and daytime sleepiness.

Methods

Prelicensure nursing students (n = 254) completed questionnaires that included demographics; obligations and behaviors that always, sometimes, or never caused sleep loss on a daily or weekly basis; the Pittsburgh Sleep Quality Index; the Epworth Sleepiness Scale; and the Sleep Hygiene Index.

Results

College classes were the most frequent reason why participants always lost sleep. Obligations of work, classes, and technology use into the night significantly predicted sleep hygiene; obligations of work, family, activity with friends, and classes significantly predicted sleep quality.

Conclusion

There is a need for education about behaviors and obligations that impact sleep in undergraduate nursing students, along with resources to assist in coping with external stressors.
Evaluation of WGS performance for bacterial pathogen characterization with the Illumina technology optimized for time-critical situations
Authors: Bogaerts Bert , Winand Raf , Van Braekel Julien , Hoffman Stefan , Roosens Nancy H. C. , De Keersmaecker Sigrid C. J. , Marchal Kathleen , Vanneste Kevin
Published: November 2021

Whole genome sequencing (WGS) has become the reference standard for bacterial outbreak investigation and pathogen typing, providing a resolution unattainable with conventional molecular methods. Data generated with Illumina sequencers can however only be analysed after the sequencing run has finished, thereby losing valuable time during emergency situations. We evaluated both the effect of decreasing overall run time, and also a protocol to transfer and convert intermediary files generated by Illumina sequencers enabling real-time data analysis for multiple samples part of the same ongoing sequencing run, as soon as the forward reads have been sequenced. To facilitate implementation for laboratories operating under strict quality systems, extensive validation of several bioinformatics assays (16S rRNA species confirmation, gene detection against virulence factor and antimicrobial resistance databases, SNP-based antimicrobial resistance detection, serotype determination, and core genome multilocus sequence typing) for three bacterial pathogens (

Mycobacterium tuberculosis

,

Neisseria meningitidis

, and Shiga-toxin producing

Escherichia coli

) was performed by evaluating performance in function of the two most critical sequencing parameters, i.e. read length and coverage. For the majority of evaluated bioinformatics assays, actionable results could be obtained between 14 and 22 h of sequencing, decreasing the overall sequencing-to-results time by more than half. This study aids in reducing the turn-around time of WGS analysis by facilitating a faster response in time-critical scenarios and provides recommendations for time-optimized WGS with respect to required read length and coverage to achieve a minimum level of performance for the considered bioinformatics assay(s), which can also be used to maximize the cost-effectiveness of routine surveillance sequencing when response time is not essential.
At the metal–metabolite interface in Aspergillus fumigatus: towards untangling the intersecting roles of zinc and gliotoxin
Authors: Traynor Aimee M. , Owens Rebecca A. , Coughlin Claudia M. , Holton Maeve C. , Jones Gary W. , Calera José A. , Doyle Sean
Published: November 2021

Cryptic links between apparently unrelated metabolic systems represent potential new drug targets in fungi. Evidence of such a link between zinc and gliotoxin (GT) biosynthesis in Aspergillus fumigatus is emerging. Expression of some genes of the GT biosynthetic gene cluster gli is influenced by the zinc-dependent transcription activator ZafA, zinc may relieve GT-mediated fungal growth inhibition and, surprisingly, GT biosynthesis is influenced by zinc availability. In A. fumigatus, dithiol gliotoxin (DTG), which has zinc-chelating properties, is converted to either GT or bis-dethiobis(methylthio)gliotoxin (BmGT) by oxidoreductase GliT and methyltransferase GtmA, respectively. A double deletion mutant lacking both GliT and GtmA was previously observed to be hypersensitive to exogenous GT exposure. Here we show that compared to wild-type exposure, exogenous GT and the zinc chelator N,N,N′,N′-tetrakis(2-pyridinylmethyl)−1,2-ethanediamine (TPEN) inhibit A. fumigatus ΔgliTΔgtmA growth, specifically under zinc-limiting conditions, which can be reversed by zinc addition. While GT biosynthesis is evident in zinc-depleted medium, addition of zinc (1 µM) suppressed GT and activated BmGT production. In addition, secretion of the unferrated siderophore, triacetylfusarinine C (TAFC), was evident by A. fumigatus wild-type (at >5 µM zinc) and ΔgtmA (at >1 µM zinc) in a low-iron medium. TAFC secretion suggests that differential zinc-sensing between both strains may influence fungal Fe3+ requirement. Label-free quantitative proteomic analysis of both strains under equivalent differential zinc conditions revealed protein abundance alterations in accordance with altered metabolomic observations, in addition to increased GliT abundance in ΔgtmA at 5 µM zinc, compared to wild-type, supporting a zinc-sensing deficiency in the mutant strain. The relative abundance of a range of oxidoreductase- and secondary metabolism-related enzymes was also evident in a zinc- and strain-dependent manner. Overall, we elaborate new linkages between zinc availability, natural product biosynthesis and oxidative stress homeostasis in A. fumigatus.
A positively Tuned Voltage Indicator Reveals Electrical Correlates of Calcium Activity in the Brain
Authors: Evans S. Wenceslao , Shi Dongqing , Chavarha Mariya , Plitt Mark H. , Taxidis Jiannis , Madruga Blake , van Keulen Siri C. , Pang Michelle M. , Su Sharon , Hwang Fuu-Jiun , Zhang Guofeng , Reese Austin , Pradhan Lagnajeet , Fan Jiang Lan , Lee Sungmoo , Liu Yu , Suomivuori Carl-Mikael , Jiang Dongyun , Negrean Adrian , Wang Sui , Ji Na , Clandinin Thomas R. , Dror Ron O. , Bi Guoqiang , Makinson Christopher D. , Golshani Peyman , Giocomo Lisa M. , Losonczy Attila , Ding Jun B. , Lin Michael Z.
Published: November 2021

Neuronal spiking activity is routinely recorded using genetically encoded calcium indicators (GECIs), but calcium imaging is limited in temporal resolution and does not report subthreshold voltage changes. Genetically encoded voltage indicators (GEVIs) offer better temporal resolution and subthreshold sensitivity, but spike detection with fast GEVIs has required specialized imaging equipment. Here, we report the ASAP4 subfamily of genetically encoded voltage indicators (GEVIs) that brighten in response to membrane depolarization, inverting the fluorescence-voltage relationship of previous ASAP GEVIs. Two variants, ASAP4b and ASAP4e, feature 128% and 178% fluorescence increases over 100-mV of depolarization, respectively, facilitating spike detection in single trials in vivo with standard 1 and 2-photon imaging systems. Simultaneous voltage and calcium imaging confirms improved temporal resolution and spike discernment by ASAP4 GEVIs. Thus, positively tuned ASAP4 voltage indicators enable recording of neuronal spiking activity using similar equipment as calcium imaging, while providing higher temporal resolution.

One Sentence Summary

Upward ASAPs increase detection capability of GEVIs in vivo.
Machine Learning in the analysis of lethality and evolution of infection by the SARS-CoV-2 virus (COVID-19) in workers of the Mexico City Metro
Authors: García Islas Eréndira Itzel , de Anda Jáuregui Guillermo , Rodríguez Joaquín Salas , Soto Florencia Serranía
Published: November 2021

In terms of the number of fatalities, Mexico has been one of the countries most affected worldwide by the pandemic. Using different Machine Learning techniques, some of the first cases of the infection registered in Mexico City (CDMX), the geographical and political center of the country, are analyzed in order to determine the causes of lethality and evolution of infection by the SARS-CoV-2 virus, from April 1 to September 27, 2020 in workers of the Capital Metro.
Defining the architecture of cerebrospinal fluid cellular communities in neuroinflammatory diseases
Authors: Roostaei Tina , Diaconu Claudiu , Touil Hanane , Harbison Claire , Zhang Ya , Epstein Samantha , Tuddenham John , Thakur Kiran , Bryois Julien , Wiendl Heinz , Meyer Zu Hörste Gerd , Malhotra Dheeraj , Riley Claire , Menon Vilas , De Jager Philip L.
Published: November 2021

Cerebrospinal fluid (CSF) biomarkers are important for multiple sclerosis (MS) diagnosis. Moreover, absent of autopsy or biopsy tissue, CSF is the most relevant source for studying the immune cells involved in MS pathophysiology. Single-cell RNA sequencing (scRNA-seq) provides new opportunities to advance our understanding of disease-associated changes in CSF immune cells. Here, using scRNA-seq data generated from 58 CSF and 10 PBMC samples, we provide an updated atlas of the immune cells present in human CSF in MS and other neuroinflammatory conditions, including novel lymphoid and myeloid cell clusters. Our atlas can thus serve as a reference for future studies of immune cells in neuroinflammation. Our further characterization of CSF myeloid cells suggests that most CSF microglia-like cells resemble two of the previously-described brain microglia signatures. Additionally, our data from a sex-mismatched bone marrow transplant recipient suggest that CSF microglia-like cells are of peripheral origin. Our comparisons between MS and other neuroinflammatory disorders show a highly-specific increase in plasma cells, along with reductions in the proportion of microglia-like cells in MS CSF. Furthermore, our analyses on MS patients receiving anti-CD20 therapy ocrelizumab suggest that the treatment effects are not limited to B cell depletion, and ocrelizumab appears to reverse some MS-associated T and myeloid changes in CSF. Finally, we utilized our atlas to prioritize (1) CSF cell types expressing genes associated with MS susceptibility, and (2) ligand-receptor gene pairs that are differentially expressed in MS CSF, providing targets for further mechanistic and causal investigations in pathophysiology and treatment of MS.
Cohort profile: the Swiss Cerebral Palsy Registry (Swiss-CP-Reg) cohort study
Authors: Belle Fabiën N. , Hunziker Sandra M. , Fluss Joël , Grunt Sebastian , Juenemann Stephanie , Kuenzle Christoph , Meyer-Heim Andreas , Newman Christopher J. , Ramelli Gian Paolo , Weber Peter , Kuehni Claudia E. , Tscherter Anne
Published: November 2021

BACKGROUND

Cerebral Palsy (CP) is a group of permanent disorders of movement and posture that follows injuries to the developing brain. It results in motor dysfunction and a wide variety of comorbidities like epilepsy, pain, speech, hearing and vision disorders, cognitive dysfunction, and eating and digestive difficulties. Central data collection is essential to study the epidemiology, clinical presentations, care, and quality of life of patients affected by CP. CP specialists founded the Swiss Cerebral Palsy Registry (Swiss-CP-Reg) in 2017. This paper describes the design, structure, aims and achievements of the Swiss-CP-Reg and presents first results.

METHODS

Swiss-CP-Reg records patients of any age suffering from CP who are born, treated, or live in Switzerland. It collects data from medical records and reports, from questionnaires answered by patients and their families, and from data linkage with routine statistics and other registries. The registry contains information on diagnosis, clinical presentation, comorbidities, therapies, personal information, family history, and quality of life.

Results

From August 2017 to August 2021, 546 participants (55% males, mean age at registration 8 years (interquartile range [IQR]: 5-12) were enrolled in Swiss-CP-Reg. Most had been born at term (56%), were less than 2 years old at diagnosis (73%, median 9 months, IQR: 18-25), and were diagnosed with spastic CP (76%). Most (59%) live with a mild motor impairment (Gross Motor Function Classification System [GMFCS] level I or II), 12% with a moderate motor impairment (GMFCS level III), and 29% with a severe motor impairment (GMFCS level IV or V). In a subset of 170 participants, we measured intelligence quotient (IQ) and saw a reduced IQ by GMFCS scale increase. The Swiss-CP-Reg has a strong interest in research with currently 5 nested projects running, and many more planned.

CONCLUSIONS

Swiss-CP-Reg collects and exchanges national data on people living with CP to answer clinically relevant questions. Its structure enables retrospective and prospective data collection and knowledge exchange between experts to optimise and standardise treatment and improve the health and quality of life of those diagnosed with CP in Switzerland.

ClinicalTrials.gov identifier

NCT04992871
Comparing protein-protein interaction networks of SARS-CoV-2 and (H1N1) influenza using topological features
Authors: Khojasteh Hakimeh , Khanteymoori Alireza , Olyaee Mohammad Hossein
Published: November 2021

Background

SARS-CoV-2 pandemic first emerged in late 2019 in China. It has since infected more than 183 million individuals and caused about 4 million deaths globally. A protein-protein interaction network (PPIN) and its analysis can provide insight into the behavior of cells and lead to advance the procedure of drug discovery. The identification of essential proteins is crucial to understand for cellular survival. There are many centrality measures to detect influential nodes in complex networks. Since SARS-CoV-2 and (H1N1) influenza PPINs pose 553 common proteins. Analyzing influential proteins and comparing these networks together can be an effective step helping biologists in drug design.

Results

We used 21 centrality measures on SARS-CoV-2 and (H1N1) influenza PPINs to identify essential proteins. PCA-based dimensionality reduction was applied on normalized centrality values. Some measures demonstrated a high level of contribution in comparison to others in both PPINs, like Barycenter, Decay, Diffusion degree, Closeness (Freeman), Closeness (Latora), Lin, Radiality, and Residual. Using validation measures, the appropriate clustering method was chosen for centrality measures. We also investigated some graph theory-based properties like the power law, exponential distribution, and robustness.

Conclusions

Through analysis and comparison, both networks exhibited remarkable experimental results. The network diameters were equal and in terms of heterogeneity, SARS-CoV-2 PPIN tends to be more heterogeneous. Both networks under study display a typical power-law degree distribution. Dimensionality reduction and unsupervised learning methods were so effective to reveal appropriate centrality measures.
Ultrapotent and Broad Neutralization of SARS-CoV-2 Variants by Modular, Tetravalent, Bi-paratopic Antibodies
Authors: Miersch Shane , Saberianfar Reza , Chen Chao , Sharma Nitin , Amarasinghe Gaya K. , Caccuri Francesca , Zani Alberto , Caruso Arnaldo , Novelli Giuseppe , Sidhu Sachdev S
Published: November 2021

Neutralizing antibodies (nAbs) that target the SARS-CoV-2 spike protein are approved for treatment of COVID-19. However, with the emergence of variants of concern, there is a need for new treatment options. We report a novel format that enables modular assembly of bi-paratopic, tetravalent nAbs with antigen-binding sites from two distinct nAbs. The tetravalent nAb was purified in high yield, and it exhibited biophysical characteristics that were comparable to those of approved therapeutic antibodies. The tetravalent nAb bound to the spike protein trimer at least 100-fold more tightly than bivalent IgGs (apparent KD < 1 pM), and it exhibited extremely high potencies against a broad array of pseudoviruses, chimeric viruses, and authentic virus variants. Together, these results establish the tetravalent diabody-Fc-Fab as a robust, modular platform for rapid production of drug-grade nAbs with potencies and breadth of coverage that greatly exceed those of conventional bivalent IgGs.
Influence of heterogeneous age-group contact patterns on critical vaccination rates for herd immunity to SARS-CoV-2
Authors: Saldaña Joan , Scoglio Caterina
Published: November 2021

Currently, several western countries have more than half of their population fully vaccinated against COVID-19. At the same time, some of them are experiencing a fourth or even a fifth wave of cases, most of them concentrated in sectors of the populations whose vaccination coverage is lower than the average. So, the initial scenario of vaccine prioritization has given way to a new one where achieving herd immunity is the primary concern. Using an age-structured vaccination model with waning immunity, we show that, under a limited supply of vaccines, a vaccination strategy based on minimizing the basic reproduction number allows for the deployment of a number of vaccine doses lower than the one required for maximizing the vaccination coverage. Such minimization is achieved by giving greater protection to those age groups that, for a given social contact pattern, have smaller fractions of susceptible individuals at the endemic equilibrium without vaccination, that is, to those groups that are more vulnerable to infection.