bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulsar observations at low frequencies: applications to pulsar timing and solar wind models
Authors: Kumar P , White S M , Stovall K , Dowell J , Taylor G B
Published: February 2022

Efforts are underway to use high-precision timing of pulsars in order to detect low-frequency gravitational waves. A limit to this technique is the timing noise generated by dispersion in the plasma along the line of sight to the pulsar, including the solar wind. The effects due to the solar wind vary with time, influenced by the change in solar activity on different time-scales, ranging up to ∼11 yr for a solar cycle. The solar wind contribution depends strongly on the angle between the pulsar line of sight and the solar disc, and is a dominant effect at small separations. Although solar wind models to mitigate these effects do exist, they do not account for all the effects of the solar wind and its temporal changes. Since low-frequency pulsar observations are most sensitive to these dispersive delays, they are most suited to test the efficacy of these models and identify alternative approaches. Here, we investigate the efficacy of some solar wind models commonly used in pulsar timing using long-term, high-cadence data on six pulsars taken with the Long Wavelength Array, and compare them with an operational solar wind model. Our results show that stationary models of the solar wind correction are insufficient to achieve the timing noise desired by pulsar timing experiments, and we need to use non-stationary models, which are informed by other solar wind observations, to obtain accurate timing residuals.
The structure of AcrIE4-F7 reveals a common strategy for dual CRISPR inhibition by targeting PAM recognition sites
Authors: Hong Sung-Hyun , Lee Gyujin , Park Changkon , Koo Jasung , Kim Eun-Hee , Bae Euiyoung , Suh Jeong-Yong
Published: February 2022

Bacteria and archaea use the CRISPR-Cas system to fend off invasions of bacteriophages and foreign plasmids. In response, bacteriophages encode anti-CRISPR (Acr) proteins that potently inhibit host Cas proteins to suppress CRISPR-mediated immunity. AcrIE4-F7, which was isolated from Pseudomonas citronellolis, is a fused form of AcrIE4 and AcrIF7 that inhibits both type I-E and type I-F CRISPR-Cas systems. Here, we determined the structure of AcrIE4-F7 and identified its Cas target proteins. The N-terminal AcrIE4 domain adopts a novel α-helical fold that targets the PAM interaction site of the type I-E Cas8e subunit. The C-terminal AcrIF7 domain exhibits an αβ fold like native AcrIF7, which disables target DNA recognition by the PAM interaction site in the type I-F Cas8f subunit. The two Acr domains are connected by a flexible linker that allows prompt docking onto their cognate Cas8 targets. Conserved negative charges in each Acr domain are required for interaction with their Cas8 targets. Our results illustrate a common mechanism by which AcrIE4-F7 inhibits divergent CRISPR-Cas types.
Visual Attention to Health Warning Labels on Waterpipe Venue Menus in Immersive Virtual Reality
Authors: Kidanu Azieb W , Shi Rui , Cruz-Cano Raul , Feldman Robert H , Butler James , Dyer Typhanye V , Fryer Craig S , Varshney Amitabh , Lee Eric , Clark Pamela I
Published: February 2022

Introduction

This study examined how health warning labels (HWL) on a waterpipe venue menu captured and held the attention of consumers and influenced waterpipe tobacco smoking (WTS) attitudes, beliefs, and behaviors.

Aims and Methods

A randomized experiment (N = 96) of young adult waterpipe smokers was conducted in an immersive virtual reality laboratory. Participants viewed one of two virtual reality scenarios, a menu with an HWL and nicotine concentration or menu without an HWL and nicotine concentration. Eye-tracking metrics were collected, and participants completed posttest questionnaires on demographics, tobacco use history, and WTS attitudes, beliefs, and behaviors. T-tests were used to assess group differences, and a mediation analysis conducted to examine the relationship between the HWL and intention to quit WTS.

Results

Participants in the HWL group demonstrated greater visual attention to the warning and nicotine areas and less visual attention to the flavor and ingredients areas of the menu compared to the control group. The HWL group demonstrated greater negative attitudes toward WTS (p = .002), greater perceived risk of decreased lung function (p = .026), and greater intention to quit WTS (p = 0.003). The mediation model indicated the relationship between the HWL on a menu and intention to quit WTS was mediated by an increase in negative attitudes toward WTS.

Conclusions

The HWLs on a menu captured and held the attention of consumers and increased negative attitudes, perceptions of health risk, and intention to quit WTS indicating potential benefit of including a warning label or nicotine concentration on menus to correct misperceptions of WTS.

Implications

The study contributes to the broader literature on communicating the harms and risks of WTS. The findings suggest that HWL and nicotine concentration on waterpipe venue menus attract attention from consumers in environments comparable to the real world and the strategy warrants further exploration as a targeted policy intervention to educate the public and reduce the health burden of WTS.
Predictors of social participation: evidence from repeated cross-sectional population surveys in England
Authors: Wilding A , Munford L A , Sutton M
Published: February 2022

Background

Social participation is linked to better health and well-being. However, there is limited research on the individual and area-level predictors of participation. This study aims to determine the characteristics associated with participation, particularly the impact of community asset availability.

Methods

We used data from 34 582 adult respondents to the nationally representative Community Life Survey from 2013 to 2018. We measured social participation by reported participation in 15 types of groups. We used probit and negative binomial regression models and included a wide range of individual, household and area characteristics, and availability of 14 types of community assets.

Results

The following characteristics were associated with higher levels of participation: being female (+3.0 percentage points (p.p.) (95% CI 1.8 to 4.1p.p.), Black, Asian or Minority Ethnicity (+3.7p.p. (1.9 to 5.5p.p.)), homeownership (+4.1 p.p. (2.7 to 5.6p.p.)) and living in a rural area (+2.1p.p. (0.5 to 3.6p.p)). Respondents from the most deprived areas were less likely to participate than those in average deprivation areas (−3.9p.p. (−5.9 to −1.99p.p.)). Higher availability of community assets was associated with increased participation in groups. The effect of availability on participation varied by type of asset.

Conclusion

Improving community assets infrastructure in high deprivation and urban areas would encourage more social participation in these areas.
nQMaker: Estimating Time Nonreversible Amino Acid Substitution Models
Authors: Dang Cuong Cao , Minh Bui Quang , McShea Hanon , Masel Joanna , James Jennifer Eleanor , Vinh Le Sy , Lanfear Robert
Published: February 2022

Amino acid substitution models are a key component in phylogenetic analyses of protein sequences. All commonly used amino acid models available to date are time-reversible, an assumption designed for computational convenience but not for biological reality. Another significant downside to time-reversible models is that they do not allow inference of rooted trees without outgroups. In this article, we introduce a maximum likelihood approach nQMaker, an extension of the recently published QMaker method, that allows the estimation of time nonreversible amino acid substitution models and rooted phylogenetic trees from a set of protein sequence alignments. We show that the nonreversible models estimated with nQMaker are a much better fit to empirical alignments than pre-existing reversible models, across a wide range of data sets including mammals, birds, plants, fungi, and other taxa, and that the improvements in model fit scale with the size of the data set. Notably, for the recently published plant and bird trees, these nonreversible models correctly recovered the commonly estimated root placements with very high-statistical support without the need to use an outgroup. We provide nQMaker as an easy-to-use feature in the IQ-TREE software (http://www.iqtree.org), allowing users to estimate nonreversible models and rooted phylogenies from their own protein data sets. The data sets and scripts used in this article are available at https://doi.org/10.5061/dryad.3tx95x6hx. [amino acid sequence analyses; amino acid substitution models; maximum likelihood model estimation; nonreversible models; phylogenetic inference; reversible models.]
Should trustees invest in sustainability-linked bonds?
Authors: Broadway Luke
Published: February 2022

This article considers the suitability of sustainability-linked bonds as trust investments. Particular focus is placed on the coupon ratchet, and whether the engagement of the ratchet operates in accordance with a trustee’s duties.
Advanced Integrated Science Courses: Building a Skill Set to Engage With the Interface of Research and Medicine
Authors: Miloslavsky Eli M. , Besche Henrike C. , Calderwood Stephen B. , Chang Bernard S. , Dienstag Jules L. , King Randall W. , Mitchell Richard N. , Schwartzstein Richard M. , Thomas Horatio , Hundert Edward M. , Flanagan John G. ,   for the Advanced Integrated Science Courses Working Group
Published: February 2022

Scientific research has been changing medical practice at an increasing pace. To keep up with this change, physicians of the future will need to be lifelong learners with the skills to engage with emerging science and translate it into clinical care.

How medical schools can best prepare students for ongoing scientific change remains unclear. Adding to the challenge is reduced time allocated to basic science in curricula and rapid expansion of relevant scientific fields. A return to science with greater depth after clinical clerkships has been suggested, although few schools have adopted such curricula and implementation can present challenges.

The authors describe an innovation at Harvard Medical School, the Advanced Integrated Science Courses (AISCs), which are taken after core clerkships. Students are required to take 2 such courses, which are offered in a variety of topics. Rather than factual content, the learning objectives are a set of generalizable skills to enable students to critically evaluate emerging research and its relationship to medical practice. Making these generalizable skills the defining principle of the courses has several important advantages: it allows standardization of acquired skills to be combined with diverse course topics ranging from basic to translational and population sciences; students can choose courses and projects aligned with their interests, thereby enhancing engagement, curiosity, and career relevance; schools can tailor course offerings to the interests of local faculty; and the generalizable skills delineate a unique purpose of these courses within the overall medical school curriculum.

For the 3 years AISCs have been offered, students rated the courses highly and reported learning the intended skill set effectively. The AISC concept addresses the challenge of preparing students for this era of rapidly expanding science and should be readily adaptable to other medical schools.
Postoperative Infection: Prevention, Diagnosis, and Treatment Guidelines for the Sports Surgeon
Authors: Pullen W. Michael , Money Adam J. , Ray Taylor E. , Freehill Michael T. , Sherman Seth L.
Published: February 2022

Postoperative infection remains a potentially devastating complication facing the sports medicine surgeon. Infection prevention begins with a thorough history and physical examination to identify patient specific risk factors and aid in risk stratification. Perioperative steroid injections should be used cautiously, with increased time prior to or following surgery being associated with lower infection risk. Sterile preparation with an alcohol containing solution is typically preferred, though there is limited evidence to identify which product is superior. Diagnosis can be challenging with a high index of suspicion needed to identify and appropriately manage patients. Treatment involves prompt irrigation and debridement with deep cultures. Antibiotic coverage should begin with empiric broad treatment and be tailored based on culture results. Early consultation with an infectious disease specialist is recommended to ensure appropriate antibiotic coverage and duration of treatment.
Late responses in the anterior insula reflect the cognitive component of pain: evidence of nonpain processing
Authors: Taniguchi Nami , Hironaga Naruhito , Mitsudo Takako , Tamura Shunsuke , Yamaura Ken , Tobimatsu Shozo
Published: February 2022

Introduction:

Pain is a complex experience influenced by sensory and psychological factors. The insula is considered to be a core part of the pain network in the brain. Previous studies have suggested a relationship between the posterior insula (PI) and sensory processing, and between the anterior insula (AI) and cognitive–affective factors.

Objectives:

Our aim was to distinguish sensory and cognitive responses in pain-related insular activities.

Methods:

We recorded spatiotemporal insular activation patterns of healthy participants (n = 20) during pain or tactile processing with painful or nonpainful movie stimuli, using a magnetoencephalography. We compared the peak latency between PI and AI activities in each stimulus condition, and between pain and tactile processing in each response. The peak latency and amplitude between different movies were then examined to explore the effects of cognitive influence. A visual analogue scale was used to assess subjective perception.

Results:

The results revealed one clear PI activity and 2 AI activities (early and late) in insular responses induced by pain/tactile stimulation. The early response transmitted from the PI to AI was observed during sensory-associated brain activity, whereas the late AI response was observed during cognitive-associated activity. In addition, we found that painful movie stimuli had a significant influence on both late AI activity and subjective perception, caused by nonpainful actual stimulation.

Conclusions:

The current findings suggested that late AI activation reflects the processing of cognitive pain information, whereas the PI and early AI responses reflect sensory processing.
Increasing numbers of killer whale individuals use fisheries as feeding opportunities within subantarctic populations
Authors: Amelot Morgane , Plard Floriane , Guinet Christophe , Arnould John P. Y. , Gasco Nicolas , Tixier Paul
Published: February 2022

Fisheries can generate feeding opportunities for large marine predators in the form of discards or accessible catch. How the use of this anthropogenic food may spread as a new behaviour, across individuals within populations over time, is poorly understood. This study used a 16-year (2003–2018) monitoring of two killer whaleOrcinus orcasubantarctic populations (regularandType-Dat Crozet), and Bayesian multistate capture–mark–recapture models, to assess temporal changes in the number of individuals feeding on fish caught on hooks (‘depredation’ behaviour) of a fishery started in 1996. For both populations, the number of depredating individuals increased during the study period (34 to 94 forregular; 17 to 43 forType-D). Increasing abundance is unlikely to account for this and, rather, the results suggest depredation was acquired by increasing numbers of existing individuals. Forregularkiller whales, a plateau reached from 2014 suggests that it took 18 years for the behaviour to spread across the whole population. A more recent plateau was apparent forType-Ds but additional years are needed to confirm this. These findings show how changes in prey availability caused by human activities lead to rapid, yet progressive, innovations in killer whales, likely altering the ecological role of this top-predator.
Idiosyncratic learning performance in flies
Authors: Smith Matthew A.-Y. , Honegger Kyle S. , Turner Glenn , de Bivort Benjamin
Published: February 2022

Individuals vary in their innate behaviours, even when they have the same genome and have been reared in the same environment. The extent of individuality in plastic behaviours, like learning, is less well characterized. Also unknown is the extent to which intragenotypic differences in learning generalize: if an individual performs well in one assay, will it perform well in other assays? We investigated this using the fruit fly
Drosophila melanogaster
, an organism long-used to study the mechanistic basis of learning and memory. We found that isogenic flies, reared in identical laboratory conditions, and subject to classical conditioning that associated odorants with electric shock, exhibit clear individuality in their learning responses. Flies that performed well when an odour was paired with shock tended to perform well when the odour was paired with bitter taste or when other odours were paired with shock. Thus, individuality in learning performance appears to be prominent in isogenic animals reared identically, and individual differences in learning performance generalize across some aversive sensory modalities. Establishing these results in flies opens up the possibility of studying the genetic and neural circuit basis of individual differences in learning in a highly suitable model organism.
Allee effects and the Allee-effect zone in northwest Atlantic cod
Authors: Perälä Tommi , Hutchings Jeffrey A. , Kuparinen Anna
Published: February 2022

According to the theory of compensatory dynamics, depleted populations should recover when the threat responsible for their decline is removed because
per capita
population growth is assumed to be highest when populations are at their smallest viable sizes. Yet, many seriously depleted fish populations have failed to recover despite threat mitigation. Atlantic cod (
Gadus morhua
) stocks off Newfoundland, despite 30 years of dramatically reduced fishing mortality and numerous fishery closures, have not recovered, suggesting that drivers other than fishing can regulate the growth of collapsed fish populations, inhibiting or preventing their recovery. Here, using Bayesian inference, we show strong evidence of Allee effects in a south Newfoundland cod population, based on data on recruitment and spawning stock biomass. We infer the Allee-effect threshold, below which recovery is impaired. We demonstrate the necessity of data at low population sizes to make inferences about the nature of low-abundance dynamics. Our work indicates that Allee effects are not negligible in commercially exploited fish populations, as commonly projected, and that they represent an inhibitory force that can effectively prevent recovery from overfishing. Our findings contrast with prevailing fisheries management practices that assume compensatory dynamics at low abundances with potential to seriously overestimate the recovery potential of collapsed populations.
In vitro
cell composition identification of wood decay fungi by Fourier transform infrared spectroscopy
Authors: Gupta Barun Shankar , Jelle Bjørn Petter , Gao Tao
Published: February 2022

Decay pathogens follow dissimilar metabolic mechanisms to cause irreversible damage to woody tissues. The objective of this study is to perform inter- and intra-species microbial cell structural comparison using attenuated total reflectance Fourier transform infrared spectroscopy. Representative fungi species, causing brown rot and white rot, namely,
Postia placenta
and
Trametes versicolor
, respectively, were cultured in laboratory conditions.
In vitro
spectral measurements were performed at periodic two week intervals of fungal growth. The study shows structural differences for both species of fungi. The prominent presence of protein amide, carbohydrate and carboxyl bands was of interest. Spectral deconvolution of the infrared broadband around approximately 3300 cm
−1
produced peaks at four different wavenumbers. The hydrogen bond energy obtained at the four wavenumbers, from deconvolution, varied from approximately 41 kJ mol
−1
to approximately 7 kJ mol
−1
, indicating the presence of strong and weak forces in microbial cell structure. The hydrogen bond distance, obtained at the deconvoluted wavenumbers, varied between 2.7 Å–2.8 Å, indicating the presence of short and long-distance forces within microbial cells. Microscopic observation showed mycelium colonization, hyphal tip and lateral branching.
Battery characterization for wireless sensor network applications to investigate the effect of load on surface temperatures
Authors: Ali Omer , Ishak Mohamad Khairi , Ooi Chia Ai , Bhatti Muhammad Kamran Liaquat
Published: February 2022

Wireless sensor networks (WSN) are commonly used in remote environments for monitoring and sensing. These devices are typically powered by batteries, the performance of which varies depending on environmental (such as temperature and humidity) as well as operational conditions (discharge rate and state-of-charge, SOC). As a result, assessing their technical viability for WSN applications requires performance evaluation based on the aforementioned stimuli. This paper proposes an efficient method for examining battery performance parameters such as capacity, open-circuit voltage (OCV) and SOC. Four battery types (lithium-ion, lithium-polymer, nickel-metal hydride and alkaline) were subjected to IEEE 802.15.4 protocol-based discharge rates to record the discharge characteristics. Furthermore, the combined effect of discharge rates on battery surface temperature and OCV variations was investigated. Shorter relaxation times (4–8 h) were observed in lithium-based batteries, resulting in faster energy recovery while maintaining rated capacity. It was observed that nearly 80% of the voltage region was flat, with minor voltage variations during the discharge cycle. Furthermore, lithium-based batteries experienced negligible changes in surface temperatures (approx. 0.03°C) with respect to discharge rates, making them the best battery choice for low-power applications such as WSNs.
Development of three ecological spectroscopic methods for analysis of betrixaban either alone or in mixture with lercanidipine: greenness assessment
Authors: El-Masry Amal A. , El-Wasseef Dalia R. , Eid Manal , Shehata Ihsan A. , Zeid Abdallah M.
Published: February 2022

Three eco-friendly spectrophotometric methods were developed for determination of the novel anticoagulant drug, betrixaban (BTX). The first method (method A) was based on direct analysis of BTX at 229.4 nm on the zero-order spectrum using methanol as the optimum solvent. While the second method (method B) was based on measuring difference absorption value (ΔA) of BTX at 335 nm, which was obtained from pH-induced spectral difference (difference spectra of BTX in 0.1 M NaOH versus 0.1 M HCl). The third method (method C) was based on measurement of the first-derivative amplitudes of BTX and its co-administered Ca channel blocker lercanidipine (LER) at 304 and 229 nm for simultaneous assay of BTX and LER, respectively. All methods were linear over concentration ranges of 1.0–20.0 and 8.0–80.0 µg ml−1for BTX in methods A and B, respectively, and of 1.0–20.0 and 1.0–25.0 µg ml−1for BTX and LER, respectively, in method C. The three methods were fully validated and assessed for greenness by three metrics: analytical eco-scale, green analytical procedure index and Analytical GREEnness metrics. The results indicated the validity and greenness of the proposed methods. Moreover, the methods were applied to assay the studied analytes in their dosage forms with high percentage of recovery and low percentage of relative s.d. values.
Drivers of diversification in freshwater gastropods vary over deep time
Authors: Neubauer Thomas A. , Hauffe Torsten , Silvestro Daniele , Scotese Christopher R. , Stelbrink Björn , Albrecht Christian , Delicado Diana , Harzhauser Mathias , Wilke Thomas
Published: February 2022

Unravelling the drivers of species diversification through geological time is of crucial importance for our understanding of long-term evolutionary processes. Numerous studies have proposed different sets of biotic and abiotic controls of speciation and extinction rates, but typically they were inferred for a single, long geological time frame. However, whether the impact of biotic and abiotic controls on diversification changes over time is poorly understood. Here, we use a large fossil dataset, a multivariate birth–death model and a comprehensive set of biotic and abiotic predictors, including a new index to quantify tectonic complexity, to estimate the drivers of diversification for European freshwater gastropods over the past 100 Myr. The effects of these factors on origination and extinction are estimated across the entire time frame as well as within sequential time windows of 20 Myr each. Our results find support for temporal heterogeneity in the factors associated with changes in diversification rates. While the factors impacting speciation and extinction rates vary considerably over time, diversity-dependence and topography are consistently important. Our study highlights that a high level of heterogeneity in diversification rates is best captured by incorporating time-varying effects of biotic and abiotic factors.
Men are less religious in more gender-equal countries
Authors: Moon Jordan W. , Tratner Adam E. , McDonald Melissa M.
Published: February 2022

Sex differences in religiosity are cross-culturally common and robust, yet it is unclear why sex differences in some cultures are larger than in others. Although women are more religious than men in most countries, religions frequently provide asymmetrical benefits to men at the expense of women. Two global analyses (51 countries and 74 countries) found that country-level gender equality was consistently and negatively associated with religiousness (i.e. religious attendance, reported importance of God and frequency of prayer) for men, more than for women, leading to a larger sex difference in religiousness in more gender-equal countries. Results were especially robust for religious attendance, and hold accounting for country-level wealth, as well as individuals' religious affiliation, the moralization of sexuality, age and education level. We interpret results through a rational choice lens, which assumes that people are more drawn to religion when it is consistent with their reproductive goals.
DNA metabarcoding reveals host-specific communities of arthropods residing in fungal fruit bodies
Authors: Lunde Lisa Fagerli , Birkemoe Tone , Kauserud Håvard , Boddy Lynne , Jacobsen Rannveig M. , Morgado Luis , Sverdrup-Thygeson Anne , Maurice Sundy
Published: February 2022

Biological communities within living organisms are structured by their host's traits. How host traits affect biodiversity and community composition is poorly explored for some associations, such as arthropods within fungal fruit bodies. Using DNA metabarcoding, we characterized the arthropod communities in living fruit bodies of 11 wood-decay fungi from boreal forests and investigated how they were affected by different fungal traits. Arthropod diversity was higher in fruit bodies with a larger surface area-to-volume ratio, suggesting that colonization is crucial to maintain arthropod populations. Diversity was not higher in long-lived fruit bodies, most likely because these fungi invest in physical or chemical defences against arthropods. Arthropod community composition was structured by all measured host traits, namely fruit body size, thickness, surface area, morphology and toughness. Notably, we identified a community gradient where soft and short-lived fruit bodies harboured more true flies, while tougher and long-lived fruit bodies had more oribatid mites and beetles, which might reflect different development times of the arthropods. Ultimately, close to 75% of the arthropods were specific to one or two fungal hosts. Besides revealing surprisingly diverse and host-specific arthropod communities within fungal fruit bodies, our study provided insight into how host traits structure communities.
Multispecialty multidisciplinary input into comorbidities in heart failure reduces hospitalisation and clinic attendance
Authors: Essa Hani , Walker Lauren , Mohee Kevin , Oguguo Emeka , Douglas Homeyra , Kahn Matthew , Rao Archana , Bellieu Julie , Hadcroft Justine , Hartshorne-Evans Nick , Bliss Janet , Akpan Asan , Wong Christopher , Cuthbertson Daniel J , Sankaranarayanan Rajiv
Published: February 2022

Aims

Heart failure (HF) is associated with multiple co-morbidities which independently influence response to treatment as well as outcomes. This retrospective observational study (January 2020-June 2021) analysed the impact of monthly virtual HF multi-specialty multi-disciplinary team (MDT) meetings to address the management of associated comorbidities and thereby upon provision, cost of care and HF outcomes.

Methods

Patients acted as their own controls, with outcomes compared for equal periods (for each patient) pre versus post-MDT meeting. The MDT comprised of HF cardiologists (primary, secondary, tertiary care), HF specialist nurses (hospital, community), nephrologist, endocrinologist, palliative care specialist, chest physician, pharmacist, clinical pharmacologist and geriatrician. Outcome measures were 1) all-cause hospitalisations, 2) outpatient clinic attendances, and 3) cost.

Results

334 patients (mean age 72.5±11 years) were discussed virtually through MDT meetings and follow-up duration was 13.9 ± 4 months. The mean age-adjusted Charlson Co-morbidity Index was 7.6 ± 2.1 and Rockwood Frailty Score was 5.5 ± 1.6. The mean number of clinic attendances prevented was 1.6 ± 0.4. The total cost of funding monthly meetings for the duration of the study was £32400 and the 64 clinic appointments generated cost £9600. The MDT meetings prevented 534 clinic appointments (cost saving £80,100) and reduced all-cause hospitalisations (pre-MDT meeting 1.1±0.4 vs. 0.6±0.1 post-MDT meeting; p<0.001), reduction of 1586 hospital bed-days and cost-savings of £634,400. The total cost-saving to the healthcare system was £672,500.

Conclusion

The HF multispecialty virtual MDT model provides integration of care across all tiers of healthcare for HF management and a holistic approach addressing associated co-morbidities. This approach can reduce the need for out-patient attendances and all-cause hospitalisations, leading to significant cost-savings.

Key questions

What is already known about this subject?

Heart failure is associated with several co-morbid health conditions (multi-morbidity) which independently influence outcomes as well as response to treatment.

What does this study add?

This study assesses the impact of multispecialty multi-morbidity input into the management of co-morbidities and thereby the effect upon all-cause outcomes.

How might this impact on clinical practice?

Results of this study illustrate that multi-speciality management of comorbidities associated with heart failure, may not only improve all-cause outcomes but could also prove to be cost-beneficial.
Integrating Multiple Imaging Modalities does not Boost Prediction of Carotid Artery Intima-Media Thickness in Midlife Adults
Authors: Sentis Amy Isabella , Rasero Javier , Gianaros Peter J. , Verstynen Timothy D.
Published: February 2022

Background

Human neuroimaging evidence suggests that cardiovascular disease (CVD) risk may relate to functional and structural features of the brain. The present study tested whether combining functional and structural (multimodal) brain measures, derived from magnetic resonance imaging (MRI), would yield a multivariate brain biomarker that reliably predicts a subclinical marker of CVD risk, carotid-artery intima-media thickness (CA-IMT).

Methods

Neuroimaging, cardiovascular, and demographic data were assessed in 324 midlife and otherwise healthy adults who were free of (a) clinical CVD and (b) use of medications for chronic illness (aged 30-51 years, 49% female). We implemented a prediction stacking algorithm that combined multimodal brain imaging measures and Framingham Risk Scores (FRS) to predict CA-IMT. We included imaging measures that could be easily obtained in clinical settings: resting state functional connectivity and structural morphology measures from T1-weighted images.

Results

Our models reliably predicted CA-IMT using FRS, as well as for several individual MRI measures; however, none of the individual MRI measures outperformed FRS. Moreover, stacking functional and structural brain measures with FRS did not boost prediction accuracy above that of FRS alone.

Conclusions

Combining multimodal functional and structural brain measures through a stacking algorithm does not appear to yield a reliable brain biomarker of subclinical CVD, as reflected by CA-IMT.
Comparative complete scheme and booster effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 infections with SARS-CoV-2 Omicron (BA.1) and Delta (B.1.617.2) variants
Authors: Kislaya Irina , Peralta-Santos André , Borges Vítor , Vieira Luís , Sousa Carlos , Ferreira Bibiana , Pelerito Ana , Gomes João Paulo , Leite Pedro Pinto , Nunes Baltazar
Published: February 2022

Introduction

Information on vaccine effectiveness and viral loads in a context of novel variants of concern (VOC) emergence is of key importance to inform public health policies. This study aimed to estimate a measure of comparative vaccine effectiveness between Omicron (BA.1) and Delta (B.1.617.2 and sub-lineages) VOC according to vaccination exposure (primary or booster) and time since primary vaccination and to compare cycle threshold (Ct) values between Omicron and Delta VOC infections according to the vaccination status as an indirect measure of viral load.

Methods

We developed a case-case study using data on RT-PCR SARS-CoV-2 positive cases notified in Portugal during weeks 49-51 2021. The odds of vaccination in Omicron cases were compared to Delta using logistic regression adjusted for age group, sex, region and week of diagnosis and laboratory of origin. RT-PCR Ct values were compared by vaccination status and variant using linear regression model.

Results

Higher odds of vaccination were observed in cases infected by Omicron (BA.1) VOC compared to Delta (B.1.617.2) VOC cases for both complete primary vaccination (OR=2.1; CI 95% :1.8 to 2.4) and booster dose (OR= 5.2; CI 95%: 3.1 to 8.8), indicating vaccine effectiveness reduction against Omicron. No differences in distribution of Ct-values between these two VOC were observed for any vaccination exposure categories.

Conclusion

Consistent lower VE was observed against Omicron infection. Complete primary vaccination may not be protective against SARS-CoV-2 infection in regions where Omicron variant is dominant, but a massive rollout of booster vaccination campaign can contribute to reduce SARS-CoV-2 incidence in the population.
SARS-CoV-2 Variant Surveillance Using Tandem Targeted RT-PCR-based Genotyping Assays and Whole Genome Sequencing
Authors: Pinkhover Nicholas P. , Sanchez Eduardo , Pontbriand Kerriann M. , Okello Kenneth , Garvey Liam M. , Fletcher Kelli P. , Pum Alex , Li Kurvin , DeOliveira Gabriel , Proctor Teddie , Feenstra Jelena D. M. , Sorel Océane , Gandhi Manoj , Auclair Jared R.
Published: February 2022

Genomic surveillance is critical for tracking SARS-CoV-2 Variants of Concern (VOC) and for rapid detection of emerging variants. Whole genome sequencing (WGS) is the predominant method for genomic surveillance; but it is a laborious process for large-scale testing. The aim of this study was to assess the performance of a PCR-based mutation panel for the discrimination of 5 known VOC; Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529). Genotyping analysis was performed on 128 SARS-CoV-2 positive samples collected at the Life Science Testing Center at Northeastern University from April-December 2021. RNA extraction was performed using MagMax™ Viral/Pathogen II Nucleic Acid Isolation Kit. SARS-CoV-2 detection was confirmed using the TaqPath™ COVID-19 Combo Kit. Variant determination was conducted using a panel of TaqMan™ SARS-CoV-2 single nucleotide polymorphism (SNP) assays. On November 25, 2021, the emerging VOC (Omicron) was reported by South Africa and the panel was quickly modified to detect Omicron by substituting P681H and K417N assays. Based on the SNP panel analysis, variant identification in 128 samples were as follows: Alpha (N=34), Beta (N=1), Gamma (N=7), Delta (N=41) and Omicron (N=21). The genotyping panel accurately assigned lineages to 104 samples, confirmed by Ion Torrent GeneStudio S5 WGS. VOC discrimination using RT-PCR genotyping is a rapid, versatile method for detecting known and emerging SARS-CoV-2 variants. The versatility of SNP panels allows monitoring of emerging strains by simple layout adaptations. RT-PCR genotyping assays can expedite variant identification, enable high-throughput variant surveillance, and support WGS prioritization for detection of new variants.
Predicting animal to human translation: A proof of concept study using qualitative comparative analysis
Authors: Leenaars Cathalijn H.C. , Teerenstra Steven , Meijboom Franck L.B. , Bleich André
Published: February 2022

Drug development suffers from high attrition rates; promising drug candidates fail in clinical trials. Low animal-to-human translation may impact attrition. We previously summarised published translational success rates, which varied from 0% to 100%. Based on analyses of individual factors, we could not predict translational success.

Several approaches exist to analyse effects of combinations of potential predictors on an outcome. In biomedical research, regression analysis (RGA) is common. However, with RGA it is challenging to analyse multiple interactions and specific configurations (≈ combinations) of variables, which could be highly relevant to translation.

Qualitative comparative analysis (QCA) is an approach based on set theory and Boolean algebra. It was successfully used to identify specific configurations of factors predicting an outcome in other fields. We reanalysed the data from our preceding review with a QCA. This QCA resulted in the following formula for successful translation:

Which means that within the analysed dataset, the combination of relative recency (∼ means not; >1999), analyses at event or study level (not at intervention level), n<75, inclusion of more than one species and quantitative (instead of binary) analyses always resulted in successful translation (>85%). Other combinations of factors showed less consistent or negative results. An RGA on the same data did not identify any of the included variables as significant contributors.

While these data were not collected with the QCA in mind, they illustrate that the approach is viable and relevant for this research field. The QCA seems a highly promising approach to furthering our knowledge on animal-to-human translation and decreasing attrition rates in drug development.
Micapipe: A Pipeline for Multimodal Neuroimaging and Connectome Analysis
Authors: Cruces Raúl R. , Royer Jessica , Herholz Peer , Larivière Sara , Vos de Wael Reinder , Paquola Casey , Benkarim Oualid , Park Bo-yong , Degré-Pelletier Janie , Nelson Mark , DeKraker Jordan , Tardif Christine , Poline Jean-Baptiste , Concha Luis , Bernhardt Boris C.
Published: February 2022

Abstract

Multimodal magnetic resonance imaging (MRI) has accelerated human neuroscience by fostering the analysis of brain structure, function, and connectivity across multiple scales and in living brains. The richness and complexity of multimodal neuroimaging, however, demands processing methods to integrate information across modalities and different spatial scales. Here, we present micapipe, an open processing pipeline for BIDS-conform multimodal MRI datasets. micapipe can generate i) structural connectomes derived from diffusion tractography, ii) functional connectomes derived from resting-state signal correlations, iii) geodesic distance matrices that quantify cortico-cortical proximity, and iv) microstructural profile covariance matrices that assess inter-regional similarity in cortical myelin proxies. These matrices are routinely generated across established 18 cortical parcellations (100-1000 parcels), in addition to subcortical and cerebellar parcellations. Results are represented on three different surface spaces (native, conte69, fsaverage5), and outputs are BIDS-conform. Processed outputs can be quality controlled at the individual and group level. micapipe was tested on several datasets and is available at https://github.com/MICA-MNI/micapipe, documented at https://micapipe.readthedocs.io/, and containerized as a BIDS App http://bids-apps.neuroimaging.io/apps/. We hope that micapipe will foster robust and integrative studies of human brain microstructure, morphology, and connectivity.
Gut-liver-axis microphysiological system for studying cellular fluidic shear stress and inter-tissue interaction
Authors: Yang Jiandong , Hirai Yoshikazu , Imamura Satoshi , Tsuchiya Toshiyuki , Tabata Osamu , Kamei Ken-ichiro
Published: February 2022

Gut-liver-axis (GLA) is a fundamental interaction between the gut and liver for maintaining human health. To clarify the physiological and pathological roles of GLA in the human body, a GLA microphysiological system (GLA-MPS) holds great potential. However, in current GLA-MPS, the importance of a physiologically relevant flow for gut and liver cells’ cultivation is not fully addressed. In addition, the integration of individual organ perfusion, circulation flow, and organ tissue functions in a single device has not been achieved. Here, we introduce a GLA-MPS by integrating two cell culture chambers with individually applied perfusion flows and a circulation channel with an on-chip pneumatic micropump under cell culture chambers via a porous membrane for interconnecting them. We analyzed the fluid shear stress (FSS) with computational fluid dynamics simulations and confirmed that the physiologically relevant FSS (i.e., 8 × 10−3 and 1.2 × 10−7 dyne cm−2) could be applied for the gut (Caco-2) and liver (HepG2) cells, respectively. Under physiologically relevant flow, the Caco-2 and HepG2 cells in the GLA-MPS maintained a cell survival rate of 95% and 92%, respectively; further, they enhanced the expression of functional proteins such as zonula occludens 1 (ZO-1) and albumin (ALB), respectively. Thus, the presented GLA-MPS can be adapted as an advanced in vitro model in a wide range of applications for disease modeling associated with inter-tissue interactions, such as fatty liver diseases.
Understanding Chicks’ Emotions: Are Eye Blinks & Facial Temperatures Reliable Indicators?
Authors: Pijpers Naomi , van den Heuvel Huib , Duncan Ian H. , Yorzinski Jessica , Neethirajan Suresh
Published: February 2022

In commercial farming systems, chicks are reared without a mother. This absence of maternal influence can cause welfare problems when the chicks become older. Chicks imprint on their mothers they are young, and this mediates their stress and fear response. It is important to recognise problems early in the development of chicks to avoid welfare issues when they are older. One way to assess welfare is by measuring affective states. Research has shown chickens can display empathy, both towards their offspring and towards conspecifics. Measures of negative and positive affective states, either behavioural or physiological, could be good welfare indicators. This study employed non-invasive methods to measure affective states in laying hen chicks. Using video and thermal imaging, it analysed temperature changes in the peripheral areas and head region as well as changes in blinking behaviour before and after exposure to a stressor. The prediction was that the temperature would decrease in the eye and peripheral regions in response to a stressor and that the blinking rate would decrease. These changes would be indicative of a negative affective state. The results showed that the eye temperature as well as the blinking rate both decreased, whereas the temperature in the head region and the beak area increased. These results could be indicative of a negative affective state.
Human immunodeficiency virus type 2 capsid protein mutagenesis reveals amino acid residues important for virus particle assembly
Authors: Yang Huixin , Talledge Nathaniel , Arndt William G. , Zhang Wei , Mansky Louis M.
Published: February 2022

Human immunodeficiency virus (HIV) Gag drives virus particle assembly. The capsid (CA) domain is critical for Gag multimerization mediated by protein-protein interactions. The Gag protein interaction network defines critical aspects of the retroviral lifecycle at steps such as particle assembly and maturation. Previous studies have demonstrated that the immature particle morphology of HIV-2 is intriguingly distinct relative to that of HIV-1. Based upon this observation, we sought to determine the amino acid residues important for virus assembly that might help explain the differences between HIV-1 and HIV-2. To do this, we conducted site-directed mutagenesis of targeted locations in the HIV-2 CA domain of Gag and analyzed various aspects of virus particle assembly. A panel of 31 site-directed mutants of residues that reside at the HIV-2 CA inter-hexamer interface, intra-hexamer interface and CA inter-domain linker were created and analyzed for their effects on the efficiency of particle production, particle morphology, particle infectivity, Gag subcellular distribution and in vitro protein assembly. Seven conserved residues between HIV-1 and HIV-2 (L19, A41, I152, K153, K157, N194, D196) and two non-conserved residues (G38, N127) were found to significantly impact Gag multimerization and particle assembly. Taken together, these observations complement structural analyses of immature HIV-2 particle morphology and Gag lattice organization as well as provide important comparative insights into the key amino acid residues that can help explain the observed differences between HIV immature particle morphology and its association with virus replication and particle infectivity.
SleepMat: A New Behavioral Analysis Software Program for Sleep and Circadian Rhythms
Authors: Sisobhan Shiju , Rosensweig Clark , Lear Bridget C , Allada Ravi
Published: February 2022

Drosophila is a premier model for the study of circadian rhythms and sleep, revealing molecular mechanisms that are conserved with vertebrates, including humans. The Drosophila Activity Monitoring (DAM) system has been employed for automated, high throughput analyses, enabling measures of a wide range of measures of circadian and sleep, including period, rhythmicity, anticipation, sleep amount, bout length, and bout number. Yet there are no publicly available programs that capture the full breadth of these measures. Here we develop a new program SleepMat that analyzes a uniquely broader range of circadian and sleep parameters. The program is built on a Matlab platform, employs an easy-to-use graphic user interface, and is highly flexible to customize data inputs. This program will enable a user-friendly high throughput analysis of a broad range of sleep and circadian parameters that can be coupled to the power of Drosophila genetics.