bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBacteria 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

Abstract

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

Abstract

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

Abstract
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.]
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.
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

Abstract

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.
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

AbstractAimsHeart 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.MethodsPatients 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.Results334 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.ConclusionThe 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 questionsWhat 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

AbstractBackgroundHuman 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).MethodsNeuroimaging, 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.ResultsOur 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.ConclusionsCombining 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

AbstractIntroductionInformation 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.MethodsWe 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.ResultsHigher 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.ConclusionConsistent 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

AbstractGenomic 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

AbstractDrug 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.