bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Expansion of SARS-CoV-2 Variants of Concern: Dispersal Patterns and Influence of Air Travel
Authors: Tegally Houriiyah , Wilkinson Eduan , Martin Darren , Moir Monika , Brito Anderson , Giovanetti Marta , Khan Kamran , Huber Carmen , Bogoch Isaac I. , San James Emmanuel , Tsui Joseph L.-H. , Poongavanan Jenicca , Xavier Joicymara S. , Candido Darlan da S. , Romero Filipe , Baxter Cheryl , Pybus Oliver G. , Lessells Richard , Faria Nuno R. , Kraemer Moritz U.G. , de Oliveira Tulio
Published: November 2022

In many regions of the world, the Alpha, Beta and Gamma SARS-CoV-2 Variants of Concern (VOCs) co-circulated during 2020-21 and fueled waves of infections. During 2021, these variants were almost completely displaced by the Delta variant, causing a third wave of infections worldwide. This phenomenon of global viral lineage displacement was observed again in late 2021, when the Omicron variant disseminated globally. In this study, we use phylogenetic and phylogeographic methods to reconstruct the dispersal patterns of SARS-CoV-2 VOCs worldwide. We find that the source-sink dynamics of SARS-CoV-2 varied substantially by VOC, and identify countries that acted as global hubs of variant dissemination, while other countries became regional contributors to the export of specific variants. We demonstrate a declining role of presumed origin countries of VOCs to their global dispersal: we estimate that India contributed <15% of all global exports of Delta to other countries and South Africa <1-2% of all global Omicron exports globally. We further estimate that >80 countries had received introductions of Omicron BA.1 100 days after its inferred date of emergence, compared to just over 25 countries for the Alpha variant. This increased speed of global dissemination was associated with a rebound in air travel volume prior to Omicron emergence in addition to the higher transmissibility of Omicron relative to Alpha. Our study highlights the importance of global and regional hubs in VOC dispersal, and the speed at which highly transmissible variants disseminate through these hubs, even before their detection and characterization through genomic surveillance.

Highlights

Global phylogenetic analysis reveals relationship between air travel and speed of dispersal of SARS-CoV-2 variants of concern (VOCs)

Omicron VOC spread to 5x more countries within 100 days of its emergence compared to all other VOCs

Onward transmission and dissemination of VOCs Delta and Omicron was primarily from secondary hubs rather than initial country of detection during a time of increased global air travel

Analysis highlights highly connected countries identified as major global and regional exporters of VOCs
School-based caries prevention and the impact on acute and chronic student absenteeism
Authors: Ruff Ryan Richard , Habib Rami , Barry-Godin Tamarinda , Niederman Richard
Published: November 2022

Background

Poor oral health is negatively associated with absenteeism, being attributed to millions of lost school days per year. The role of school-based dental programs that address oral health inequities on student attendance has not yet been explored.

Methods

CariedAwaywas a longitudinal, cluster-randomized, non-inferiority trial of preventive medicines for dental caries used in a school-based program. To explore the potential impact of caries prevention on attendance, we extracted data on average school absenteeism and the proportion of chronically absent students from publicly-available datasets maintained by the New York City Department of Education for years before, during, and after program onset. Data were obtained for all CariedAwayschools as well as a group of untreated comparator schools. Total absences and the proportion of chronically absent students were modeled using multilevel mixed effects linear and two-limit tobit regression, respectively. Multiple model specifications were considered, including exposures to time-varying treatments across multiple years. Models also included a group of untreated comparator schools.

Results

In years in which treatment was provided through a school-based comprehensive caries prevention program, schools recorded approximately 944 fewer absences than in non-treatment years (95% CI = −1739, −149). Averaged across all study years, schools receiving either treatment had 1500 fewer absences than comparator schools, but this was not statistically significant. In contrast, chronic absenteeism was found to significantly decrease in later years of the program (B = -.037, 95% CI = -.062, -.011). Removing data for years affected by COVID-19 eliminated the significant reduction in total absences during treatment years, yet still showed a marginally significant interaction for chronic absenteeism.

Discussion

Though originally designed to mitigate access barriers to critical oral healthcare, early integration of school-based dental programs may positively impact school attendance. However, concerns over the reliability of attendance records due to the closing of school facilities resulting from COVID-19 may mask the true effect.
A Mixed-Method Approach to Determining Contact Matrices in the Cox’s Bazar Refugee Settlement
Authors: Walker Joseph , Aylett-Bullock Joseph , Shi Difu , Gidraf Kahindo Maina Allen , Evers Egmond Samir , Harlass Sandra , Krauss Frank
Published: November 2022

Contact matrices are an important ingredient in age-structured epidemic models to inform the simulated spread of the disease between sub-groups of the population. These matrices are generally derived using resource-intensive diary-based surveys and few exist in the Global South or tailored to vulnerable populations. In particular, no contact matrices exist for refugee settlements - locations under-served by epidemic models in general. In this paper we present a novel, mixed-method approach, for deriving contact matrices in populations which combines a lightweight, rapidly deployable, survey with an agent-based model of the population informed by census and behavioural data. We use this method to derive the first set of contact matrices for the Cox’s Bazar refugee settlement in Bangladesh. The matrices from the refugee settlement show strong banding effects due to different age cut-offs in attendance at certain venues, such as distribution centres and religious sites, as well as the important contribution of the demographic profile of the settlement which was encoded in the model. These can have significant implications to the modelled disease dynamics. To validate our approach, we also apply our method to the population of the UK and compare our derived matrices against well-known contact matrices previously collected using traditional approaches. Overall, our findings demonstrate that our mixed-method approach can address some of the challenges of both the traditional and previously proposed agent-based approaches to deriving contact matrices, and has the potential to be rolled-out in other resource-constrained environments. This work therefore contributes to a broader aim of developing new methods and mechanisms of data collection for modelling disease spread in refugee and IDP settlements and better serving these vulnerable communities.
Predicting cognitive decline in a low-dimensional representation of brain morphology
Authors: Lamontagne-Caron Rémi , Desrosiers Patrick , Potvin Olivier , Duchesne Simon , Doyon Nicolas
Published: November 2022

Identifying early signs of neurodegeneration due to Alzheimer’s disease (AD) is a necessary first step towards preventing cognitive decline. Individual cortical thickness measures, available after processing anatomical magnetic resonance imaging (MRI), are sensitive markers of neurodegeneration. However, normal aging cortical decline and high inter-individual variability complicate the comparison and statistical determination of the impact of AD-related neurodegeneration on trajectories. In this paper, we computed trajectories in a 2D representation of a 62-dimensional manifold of individual cortical thickness measures. To compute this representation, we used a novel, nonlinear dimension reduction algorithm called Uniform Manifold Approximation and Projection (UMAP). We trained two embeddings, one on cortical thickness measurements of 6,237 cognitively healthy participants aged 18 to 100 years old and the other on 233 mild cognitively impaired (MCI) and AD participants from the longitudinal database, the Alzheimer’s Disease Neuroimaging Initiative database (ADNI). Each participant had multiple visits (n≥ 2), one year apart. The first embedding’s principal axis was shown to be positively associated (r= 0.65) with participants’ age. Data from ADNI is projected into these 2D spaces. After clustering the data, average trajectories between clusters were shown to be significantly different between MCI and AD subjects. Moreover, some clusters and trajectories between clusters were more prone to host AD subjects. This study was able to differentiate AD and MCI subjects based on their trajectory in a 2D space with an AUC of 0.80 with 10-fold cross-validation.
The spatial and temporal distribution of SARS-CoV-2 from the built environment of COVID-19 patient rooms: A multicentre prospective study
Authors: Fralick Michael , Burella Madison , Hinz Aaron , Mejbel Hebah S. , Guttman David S. , Xing Lydia , Moggridge Jason , Lapp John , Wong Alex , Nott Caroline , Harris-Linton Nicole , Kassen Rees , MacFadden Derek
Published: November 2022

Background

SARS-CoV-2 can be detected from the built environment (e.g., floors), but it is unknown how the viral burden changes over space and time surrounding an infected patient. Characterising these data can help advance our understanding and interpretation of surface swabs from the built environment.

Methods

We conducted a prospective study at two hospitals in Ontario, Canada between January 19, 2022 and February 11, 2022. We performed serial floor sampling for SARS-CoV-2 in rooms of patients newly hospitalized with COVID-19 in the past 48 hours. We sampled the floor twice daily until the occupant moved to another room, was discharged, or 96 hours had elapsed. Floor sampling locations included: 1m from the hospital bed, 2m from the hospital bed, and at the room’s threshold to the hallway (typically 3 - 5m from the hospital bed). The samples were analyzed for the presence of SARS-CoV-2 using qPCR. We calculated the sensitivity of detecting SARS-CoV-2 in a patient with COVID-19, and we evaluated how the percentage of positive swabs and the cycle threshold of the swabs changed over time. We also compared the cycle threshold between the two hospitals.

Results

Over the 6-week study period we collected 164 floor swabs from the rooms of 13 patients. The overall percentage of swabs positive for SARS-CoV-2 was 93% and the median cycle threshold (for positive swabs) was 33.7 (IQR: 30.9, 37.5). On day 0 of swabbing the percentage of swabs positive for SARS-CoV-2 was 81.1% and the median cycle threshold was 33.7 (IQR: 32.1, 38.3) compared to swabs performed on day 2 or later where the percentage of swabs positive for SARS-CoV-2 was 98.1% and the cycle threshold was 33.4 (IQR: 30.7, 35.7). We found that viral detection did not change with increasing time (since the first sample collection) over the sampling period, OR 1.65 per day (95% CI 0.68, 4.02; p = 0.27). Similarly, viral detection did not change with increasing distance from the patient’s bed (1m, 2m, or 3m), OR 0.85 per metre (95% CI 0.38, 1.88; p = 0.69). The cycle threshold was lower (e.g. more virus) in The Ottawa Hospital (median Cq 30.8) where the floors are cleaned once daily rather than the Toronto hospital (median Cq 37.3) where floors were cleaned twice daily.

Conclusions

We were able to detect SARS-CoV-2 on the floors of rooms of patients with COVID-19 and the viral burden did not vary over time or by distance from the bed. These results suggest floor swabbing for the detection of SARS-CoV-2 in a built environment such as a hospital room is both accurate and robust to variation in sampling location and duration of occupancy.
The impacts of social restrictions during the COVID-19 pandemic on the physical activity levels of over 50-year olds: the CHARIOT COVID-19 Rapid Response (CCRR) cohort study
Authors: Green Conall , Beaney Thomas , Salman David , Robb Catherine , de Jager Loots Celeste A. , Giannakopoulou Parthenia , Udeh-Momoh Chi , Ahmadi-Abhari Sara , Majeed Azeem , Middleton Lefkos T. , McGregor Alison. H.
Published: November 2022

Objectives

To quantify the associations between shielding status and loneliness at the start of the COVID-19 pandemic, and physical activity (PA) levels throughout the pandemic.

Methods

Demographic, health and lifestyle characteristics of 7748 cognitively healthy adults aged >50, and living in London, were surveyed from April 2020 to March 2021. The International Physical Activity Questionnaire (IPAQ) short-form assessed PA before COVID-19 restrictions, and up to 6 times over 11 months. Linear mixed models investigated associations between baseline shielding status, loneliness, and time-varying PA.

Results

Participants who felt ‘often lonely’ at the outset of the pandemic completed an average of 522 and 547 fewer Metabolic Equivalent of Task (MET) minutes/week (95% CI: -809, -236, p<0.001) (95% CI: -818, -275, p<0.001) than those who felt ‘never lonely’ in univariable and multivariable models adjusted for demographic factors respectively. Those who felt ‘sometimes lonely’ completed 112 fewer MET minutes/week (95% CI: -219, -5, p=0.041) than those who felt ‘never lonely’ following adjustment for demographic factors.

Participants who were shielding at the outset of the pandemic completed an average of 352 fewer MET minutes/week than those who were not (95% CI: -432, -273; p<0.001) in univariable models and 228 fewer MET minutes/week (95% CI: -307, -150, p<0.001) following adjustment for demographic factors. No significant associations were found after further adjustment for health and lifestyle factors.

Conclusions

Those shielding or lonely at pandemic onset were likely to have completed low levels of PA during the pandemic. These associations are influenced by co-morbidities and health status.
Clinical and Therapeutic Applications of Individual-level Tissue-Specific Imputed Transcriptomes
Authors: Wang Xin , Selvaggi Caitlin , Weng Lu-Chen , Jurgens Sean J. , Choi Seung Hoan , Jha Anjali , Cao Tingyi , Koyama Satoshi , Rämö Joel T. , Kany Shinwan , Ellinor Patrick T. , Foulkes Andrea S. , Lubitz Steven A.
Published: November 2022

Gene expression causally contributes to phenotypic variability. However, since tissue-specific gene expression is difficult to measure at scale, inferring phenotypic risk for individuals using expression profiles can be difficult. We statistically imputed tissue-specific gene expression for 486,452 UK Biobank participants and demonstrated its applications using rich phenotypic data in the biorepository. We performed joint analysis of transcriptome-wide association studies (TWAS) and colocalization for six traits to prioritize tissue-gene pairs for therapeutics development. Using genes identified in TWAS, we constructed imputed transcriptome risk scores and showed their predictive utility even when conditioning on genome-wide polygenic risk scores. A phenome-wide association analysis for established therapeutic targets in whole blood recapitulated known biology and prioritized repurposing potentials supported by previous literature. Our study provides evidence supporting the utility of individual-level imputed transcriptomes for discovering novel gene-tissue-phenotype trios, expression-based phenotypic risk prediction, and identifying individuals with therapeutically targetable predisposition to disease.
Real world validation of activity recognition algorithm and development of novel behavioral biomarkers of falls in aged control and movement disorder patients
Authors: Nouriani Ali , Jonason Alec , Sabal Luke , Hanson Jacob , Jean James , Lisko Thomas , Reid Emma , Moua Yeng , Rozeboom Shane , Neverman Kaiser , Stowe Casey , Rajamani Rajesh , McGovern Robert A.
Published: November 2022

The use of wearable sensors in movement disorder patients such as Parkinson’s disease (PD) and normal pressure hydrocephalus (NPH) is becoming more widespread, but most studies are limited to characterizing general aspects of mobility using smartphones. There is a need to accurately identify specific activities at home in order to properly evaluate gait and balance at home, where most falls occur.

We developed an activity recognition algorithm to classify multiple daily living activities including high fall risk activities such as sit to stand transfers, turns and near-falls using data from 5 inertial sensors placed on the chest, upper-legs and lower-legs of the subjects. The algorithm is then verified with ground truth by collecting video footage of our patients wearing the sensors at home.

Our activity recognition algorithm showed >95% sensitivity in detection of activities. Extracted features from our home monitoring system showed significantly better correlation (∼69%) with prospectively measured fall frequency of our subjects compared to the standard clinical tests (∼30%) or other quantitative gait metrics used in past studies when attempting to predict future falls over one year of prospective follow-up.

Although detecting near-falls at home is difficult, our proposed model suggests that near-fall frequency is the most predictive criterion in fall detection through correlation analysis and fitting regression models.
Prevalence and causes of blindness and visual impairment in Sudur paschim Province of Nepal
Authors: Pant Suresh Raj , Bhatta Ramesh Chandra , Bhatta Subash , Sapkota YuddhaDhoj
Published: November 2022

Aim

To determine the prevalence and causes of blindness and visual impairment among aged 50 years and older population in Sudurpaschim Province of Nepal.

Methods

A cross sectional study, among population aged 50 years and older using a random multistage cluster sampling procedure. Eligible study participants were enrolled by door-to-door enumeration. Survey team lead by an Ophthalmologist assessed visual acuity, examination of eye and data collection was carried out on tablets installed with mRAAB 7 software.

Results

The survey examined 4573 out of 4615 subjects enumerated, with a response rate 99.1%. Out of 4573 subjects, 1995 (43.63%) were male and 2578 (56.37%) were female. Among the examined, 2214 (48.4%) were between 50-59 years. The age- and sex-adjusted prevalence of blindness was 0.6% (95% CI 0.3 – 0.87).The age- and sex-adjusted prevalence of severe visual impairment, moderate visual impairment, and early visual impairment were 1.0% (95% CI 0.6 – 1.3), 5.3% (95% CI 4.5 – 6.2) and 7.0% (95% CI 6.0 – 8.0) respectively. The main causes of bilateral blindness were untreated cataract (36.4%), non-trachomatous corneal opacity (24.2%), glaucoma (21.2%), globe or central nervous system abnormalities (9.1%), age related macular degeneration (6.1%) and other posterior segment diseases (3.0%).

Conclusion

Prevalence of blindness was reduced in the province in comparison to the previous survey. Cataract remains the major cause of blindness, severe visual impairment, and moderate visual impairment followed by corneal opacities and glaucoma. The study suggests more attention to be given for cataract, corneal blindness and glaucoma in future interventions to eliminate blindness.
Variation in price of cardiovascular and diabetes medicine in Indonesia, and relationship with quality: a mixed methods study in East Java
Authors: Pisani Elizabeth , Dewi Aksari , Palagyi Anna , Praveen Devarsety , Pratita Ihsan Bachtiar Rifai , Hariadini Ayuk Lawuningtyas , Lyrawati Diana , Sujarwoto  , Maharani Asri , Tampubolon Gindo , Patel Anushka
Published: November 2022

Lower-middle income Indonesia, the world’s fourth most populous country, has struggled to contain costs in its mandatory, single-payer public health insurance system since the system’s inception in 2014. Public procurement policies radically reduced prices of most medicines in public facilities and the wider market. However, professional associations and the press have questioned the quality of these low-cost, unbranded generic medicines.

We collected 204 samples of 4 cardiovascular and 1 antidiabetic medicine from health facilities and retail outlets in East Java. We collected amlodipine, captopril, furosemide, simvastatin and glibenclamide, sampling to reflect patients’ likelihood of exposure to specific brands and outlets. We recorded sales prices and maximum retail prices, and tested medicines for dissolution and percent of labelled content, using high-performance liquid chromatography. We conducted in-depth interviews with supply chain actors.

All samples, including those provided free in public facilities, met quality specifications.

Most manufacturers make both branded and unbranded medicines. Retail prices varied widely. The median ratio of price to the lowest price for an equivalent product was 5.1, and a few brands sold for over 100 times the minimum price. Prices also varied between outlets for identical products, as retail pharmacies set prices to maximize profit. Since very low-cost medicines were universally available and of good quality, we believe richer patients who chose to buy branded products effectively protected medicine quality for poorer patients in Indonesia, because manufacturers cross-subsidize between branded and unbranded versions of the same medicine.
Impact of a multimodal hand hygiene improvement intervention in a 1000-bed hospital in Thailand: a stepped wedge cluster randomized controlled trial
Authors: Hongsuwan Maliwan , Srisamang Pramot , Nuntalohit Somboon , Luangasanatip Nantasit , Lim Cherry , Day Nicholas P. , Limmathurotsakul Direk , Cooper Ben S.
Published: November 2022

Background

Good hand hygiene compliance amongst healthcare workers is critical for patient safety and plays a central role in preventing healthcare-associated infections. The World Health Organization (WHO) recommends a multimodal strategy to improve healthcare worker hand hygiene. We aimed to evaluate the effectiveness of this strategy in a middle-income country using a stepped-wedge cluster randomized trial.

Methods

The trial was conducted between 2013 and 2015 in 58 wards in a 1000-bed hospital in Thailand. The intervention was adapted from the WHO’s Hand Hygiene Improvement Strategy and implemented by the hospital’s infection control team. The primary outcome was observed hand hygiene compliance among healthcare workers in the study wards. This study was registered atClinicalTrials.gov(NCT01933087).

Findings

During 4,230 observation sessions, 54,073 hand hygiene opportunities were identified. Hand hygiene compliance increased from 10.0% (2,660/26,482) to 11.0% (3,048/27,591) after the intervention (odds ratio [OR] 1.12; 95% CI: 1.01-1.24). Among the five moments for hand hygiene, the greatest improvement in compliance was observed in hand hygiene before patient contact (OR 1.52; 95% CI: 1.21, 1.91).

Interpretation

While hand hygiene compliance improved slightly, the intervention failed to achieve the substantial improvements that were needed. There is a need for new strategies to ensure that all hospitals in low and middle-income countries can achieve and maintain acceptable levels of hand hygiene.

Funding

Oak Foundation, MRC
Using DEPendency of association on the number of Top Hits (DEPTH) as a complementary tool to identify novel risk loci in colorectal cancer
Authors: Lai John , Wong Chi , Schmidt Daniel F. , Kapuscinski Miroslaw , Alpen Karen , MacInnis Robert J. , Buchanan Daniel D. , Win Aung K. , Figueiredo Jane , Chan Andrew T. , Harrison Tabitha A. , Hoffmeister Michael , White Emily , Marchand Loic Le , Peters Ulrike , Hopper John L. , Makalic Enes , Jenkins Mark A.
Published: November 2022

Background

DEPendency of association on the number of Top Hits (DEPTH) is an approach to identify candidate risk regions by considering the risk signals from over-lapping groups of sequential variants across the genome.

Methods

We conducted a DEPTH analysis using a sliding window of 200 SNPs to colorectal cancer (CRC) data from the Colon Cancer Family Registry (CCFR) (5,735 cases and 3,688 controls), and GECCO (8,865 cases and 10,285 controls) studies. A DEPTH score >1 was used to identify risk regions common to both studies. We compared DEPTH results against those from conventional GWAS analyses of these two studies as well as against 132 published risk regions.

Results

Initial DEPTH analysis revealed 2,622 (CCFR) and 3,686 (GECCO) risk regions, of which 569 were common to both studies. Bootstrapping revealed 40 and 49 likely risk regions in the CCFR and GECCO data sets, respectively. Notably, DEPTH identified at least 82 likely risk regions that would not be detected using conventional GWAS methods, nor had they been identified in previous CRC GWASs. We found four reproducible risk regions (2q22.2, 2q33.1, 6p21.32, 13q14.3), with the HLA locus at 6p21 having the highest DEPTH score. The strongest associated SNPs were rs762216297, rs149490268, rs114741460, and rs199707618 for the CCFR data, and rs9270761 for the GECCO data.

Conclusion

DEPTH can identify novel likely risk regions for CRC not identified using conventional analyses of much larger datasets.

Impact

DEPTH has potential as a powerful complementary tool to conventional GWAS analyses for identifying risk regions within the genome.
Transmission prevention behaviors in US households with SARS-CoV-2 cases in 2020
Authors: Rubinstein Rebecca , Mei Wenwen , Cassidy Caitlin A. , Streeter Gabrielle , Basham Christopher , Cerami Carla , Lin Feng-Chang , Lin Jessica T. , Mollan Katie R.
Published: November 2022

Background

SARS-CoV-2 transmission frequently occurs within households, yet few studies describe which household contacts and household units are most likely to engage in transmission-interrupting behaviors.

Methods

We analyzed a COVID-19 prospective household transmission cohort in North Carolina (April-Oct 2020) to quantify changes in physical distancing behaviors among household contacts over 14 days. We evaluated which household contacts were most likely to ever mask at home and to ever share a bedroom with the index case between Days 7-14.

Results

In the presence of a household COVID-19 infection, 24% of household contacts reported ever masking at home during the week before study entry. Masking in the home between Days 7-14 was reported by 26% of household contacts, and was more likely for participants who observed their household index case wearing a mask. Participants of color and participants in high-density households were more likely to mask at home. After adjusting for race/ethnicity, living density was not as clearly associated with masking. Symptomatic household contacts were more likely to share a bedroom with the index case. Working individuals and those with comorbidities avoided sharing a bedroom with the index case.

Conclusion

In-home masking during household exposure to COVID-19 was infrequent in 2020. In light of ongoing transmission of SARS-CoV-2, these findings underscore a need for health campaigns to increase the feasibility and social desirability of in-home masking among exposed household members. Joint messaging on social responsibility and prevention of breakthrough infections, reinfections, and long COVID-19 may help motivate transmission-interruption behaviors.
Instantly adhesive and ultra-elastic patches for dynamic organ and wound repair
Authors: Chansoria Parth , Bonacquisti Emily , Heavey Mairead , Le Lina , Maruthamuthu Murali Kannan , Blackwell John , Jasiewicz Natalie , Sellers Rani S. , Maile Robert , Wallet Shannon , Egan Thomas , Nguyen Juliane
Published: November 2022

Bioadhesive materials and patches are promising alternatives to surgical sutures and staples. However, many existing bioadhesives do not meet the functional requirements of current surgical procedures and interventions. Here we present a translational patch material that exhibits: (1) instant adhesion to wet tissues (2.5-fold stronger than Tisseel, an FDA-approved fibrin glue), (2) ultra-stretchability (stretching to >300% its original length without losing elasticity), (3) compatibility with rapid photo-projection (<2 min fabrication time/patch), and (4) ability to deliver therapeutics. Using our established procedures for thein silicodesign and optimization of anisotropic-auxetic patches, we create next generation patches for instant attachment to wet and dry tissues while conforming to a broad range of organ mechanicsex vivoandin vivo. Patches coated with exosomes demonstrate robust wound healing capabilityin vivowithout inducing a foreign body response and without the need for patch removal that can cause pain and bleeding. We further demonstrate a new single material-based, void-filling auxetic patch designed for the treatment of lung puncture wounds.

Teaser

We demonstrate a sticky and highly elastic patch with conforming designs for dynamic organ repair.
A deep learning network for parallel self-denoising and segmentation in visible light optical coherence tomography of human retina
Authors: Ye Tianyi , Wang Jingyu , Yi Ji
Published: November 2022

Visible light optical coherence tomography (VIS-OCT) of human retina is an emerging imaging modality that uses shorter wavelength in visible light range than conventional near infrared (NIR) light. It provides one-micron level axial resolution to better separate stratified retinal layers, as well as microvascular oximetry. However, due to the practical limitation of laser safety and comfort, the permissible illumination power is much lower than NIR OCT which can be challenging to obtain high quality VIS-OCT images and subsequent image analysis. Therefore, improving VIS-OCT image quality by denoising is an essential step in the overall workflow in VIS-OCT clinical applications. In this paper, we provide the first VIS-OCT retinal image dataset from normal eyes, including retinal layer annotation and “noisy-clean” image pairs. We propose an efficient co-learning deep learning framework for parallel self-denoising and segmentation simultaneously. Both tasks synergize within the same network and improve each other’s performance. The significant improvement of segmentation (2% higher Dice coefficient compared to segmentation-only process) for ganglion cell layer (GCL), inner plexiform layer (IPL) and inner nuclear layer (INL) is observed when available annotation drops to 25%, suggesting an annotation-efficient training. We also showed that the denoising model trained on our dataset generalizes well for a different scanning protocol.
Expected Costs of Mental Efforts are Updated When People Exert Effort, not by Prospective Information
Authors: Nagase Asako Mitsuto , Westbrook Andrew , Onoda Keiichi , Morita Kenji , Kawagoe Toshikazu , Yamaguchi Shuhei , Akaishi Rei , Hanajima Ritsuko
Published: November 2022

To understand human behaviour, it is crucial to reveal the mechanisms by which we learn and decide about effort costs and benefits in an uncertain world. Whereas the mechanisms for reward learning are well-understood, the mechanisms for effort cost learning, and especially mental effort, remain elusive. Initially, we hypothesized that cost learning follows temporal-difference learning such that brains update expected costs when informed about upcoming effort levels. However, fMRI data revealed neural correlates of a cost-prediction error of mental effort during task execution and not in response to an effort cue about upcoming effort demands. These results imply that expected costs are updated during actual effort exertion, implying that the adaptive learning of mental effort cost does not follow traditional temporal-difference learning. This study contributes to the understanding of the neural mechanism underlying unwillingness to work, suggesting that humans learn mental effort costs only when they experience effort exertion.
Magnetic Bead Based Proximity Extension Assay for Sensitive Protein and Extracellular Vesicles Detection
Authors: Muthelo Phathutshedzo , Ebai Tonge , Doulabi Ehsan Manouchehri , Al-Amin Rasel A. , Wu Yajun , Kamali-Moghaddam Masood , Landegren Ulf
Published: November 2022

During the early stages of disease development, protein biomarkers can leak into the blood creating opportunities for early diagnosis of disease with minimally invasive sampling. These proteins biomarkers however are often masked by the presence of more abundant functional blood proteins, making specific detection a challenge with most current immunoassays. We we report on the development of a magnetic bead based solid-phase PEA (SP-PEA) for sensitive detection of proteins in plasma and serum samples. Antibody functionalized magnetic beads are used to capture the target of interest. Following capture, non-specifically bound proteins are washed off before PEA probes are added for detection of the bound proteins. Compared to hoogenous PEA, SP-PEA admits the use of larger sample volumes to increase available target molecules, higher concentration of detection reagents for more efficient formation of detection complexes and washes for removal of nonspecific background. We compared SP-PEA to solution phase PEA for the detection of cytokines: interlukin-6, interlukin-2, interlukin-4, interlukin-10 and Tumor Necrosis Factor-alpha, and we demonstrated an increased sensitivity by 15 to 60 fold in buffer and chicken serum. We further expanded SP-PEA to detect extracellular vesicles (EVs) through combinations of proteins on the surface of specific EV populations.
Rat superior colliculus encodes the transition between static and dynamic vision modes
Authors: Gil Rita , Valente Mafalda , Shemesh Noam
Published: November 2022

When visual stimuli are presented at a sufficiently high temporal frequency, visual perception shifts from the static to dynamic vision mode, thereby facilitating a continuity illusion which is key for correctly identifying continuous and moving objects and placing them in the context of the surrounding environment. However, how this continuity illusion is encoded along the entire visual pathway remains poorly understood, with disparate Flicker Fusion Frequency (FFF) thresholds measured at retinal, cortical, and behavioural levels. Here, we hypothesized that these disparities may suggest that other brain areas may be involved in encoding the shift from static to dynamic vision modes. We employ a comprehensive approach encompassing behavioural measurements, whole brain activation mapping with high fidelity functional MRI (fMRI), and local electrophysiological validation for studying the mechanisms underlying the shift from static to dynamic vision modes in the rat. Our behavioural measurements reported an FFF threshold proxy of 18±2 Hz. At the network level, functional MRI revealed that the superior colliculus (SC) exhibits marked signal transitions from positive to negative fMRI signal regimes at the behaviourally measured FFF threshold surrogates, with a strong linear correlation between fMRI signal and behaviour, while thalamic and cortical visual areas displayed a significantly poorer correlation with the behaviour. fMRI-driven neurometric curves approximated the behavioural psychometric curve in SC but not in the other visual areas. Electrophysiological recordings in SC suggested that these fMRI signals transitions arise from strong neural activation/suppression at low/high frequency regimes, respectively, and that a transition between these regimes occurs around the measured FFF threshold proxies. Lesions in V1 further reinforced that these transitions originate in SC. Combined, our data suggests a critical role for SC in encoding temporal frequency discriminations, in particular the shifts from the static to the dynamic vision modes.
Association Rule Mining of the Human Gut Microbiome
Authors: Zhang Yiyan , Ke Shanlin , Wang Xu-Wen , Liu Yang-Yu
Published: November 2022

The human gut carries a vast and diverse microbial community that is essential for human health. Understanding the structure of this complex community requires quantitative approaches. Traditional co-occurrence and correlation analyses typically focus on pair-wise relationships and ignore higher-order relationships. Association rule mining (ARM) is a well-developed technique in data mining and has been applied to human microbiome data to identify higher-order relationships. Yet, existing attempts suffer from small sample sizes and low taxonomic resolution. Here we leverage the curatedMetagenomic Database (CMD) to resolve those issues. We first infer association rules from gut microbiome samples of a large cohort of healthy individuals (n=2,815) in CMD. Then we compare those rules with that inferred from samples of individuals with different diseases: Inflammatory Bowel Disease (IBD, n=768), Colorectal cancer (CRC, n=368), Impaired Glucose Tolerance (IGT, n=199), and Type 2 Diabetes (T2D, n=164). Finally, we demonstrate that using ARM as a feature selection tool can improve the performance of microbiome-based disease classification. Together, this study provides a comprehensive study of higher-order microbial relationships in the human gut microbiome and highlights the importance of incorporating association rules in microbiome-based disease classification.
To disperse or compete? Coevolution of traits leads to a limited number of reproductive strategies
Authors: Planas-Sitjà Isaac , Monnin Thibaud , Loeuille Nicolas , Cronin Adam L
Published: November 2022

Reproductive strategies are defined by a combination of behavioural, morphological, and life-history traits. Reproductive investment and offspring propagule size are two key traits defining reproductive strategies. While a substantial amount of work has been devoted to understanding the independent fitness effects of each of these traits, it remains unclear how coevolution between them ultimately affects the evolution of reproductive strategies, and how this might influence the relationship between dispersal and environmental factors. In this study we explore how the evolution of reproductive strategies defined by these two coevolving traits is influenced by resource availability and spatial structuring of the environment using a simulation model. We find three possible equilibrium strategies across all scenarios: a competitor strategy with high reproductive investment (producing large propagules which disperse short distances), and two coloniser strategies differing in reproductive investment (both producing small propagules which disperse long distances). The possible equilibrium strategies for each scenario depended on starting conditions, spatial structure and resource availability. Evolutionary transitions between these equilibrium strategies were more likely in heterogeneous than homogeneous landscapes and at higher resource levels. Transition from coloniser strategy to competitor strategy was usually a two-step process, with changes in propagule size following initial evolution in investment. This highlights how the interaction between the two trait axes affects the evolution of reproductive strategies, particularly where fitness valleys preclude the simultaneous evolution of traits. Our results highlight the need to incorporate trait coevolution into evolutionary models to help develop a more integrative understanding of the structure of natural populations and how the interaction between traits constrains or hinders evolutionary processes.
Intraspecific variation of transposable elements reveals differences in the evolutionary history of fungal phytopathogen pathotypes
Authors: Nakamoto Anne A. , Joubert Pierre M. , Krasileva Ksenia V.
Published: November 2022

Transposable elements (TEs) contribute to intraspecific variation and play important roles in the evolution of fungal genomes. However, our understanding of the processes that shape TE landscapes is limited, as is our understanding of the relationship between TE content, population structure, and evolutionary history of fungal species. Fungal plant pathogens, which often have host-specific populations, are useful systems in which to study intraspecific TE content diversity. Here, we describe TE dynamics in five lineages ofMagnaporthe oryzae, the fungus that causes blast disease of rice, wheat, and many other grasses. We identified differences in TE content across these lineages, and showed that recent lineage-specific expansions of certain TEs have contributed to overall greater TE content in rice-infecting andSetaria-infecting lineages. We reconstructed the evolutionary histories of LTR-retrotransposon expansions and found that in some cases they were caused by complex proliferation dynamics of one element, and in others by multiple elements from an older population of TEs multiplying in parallel. Additionally, we found evidence suggesting the recent transfer of a DNA transposon between rice and wheat-infectingM. oryzaelineages, and a region showing evidence of homologous recombination between those lineages, which could have facilitated such a transfer. By investigating intraspecific TE content variation, we uncovered key differences in the proliferation dynamics of TEs in various pathotypes of a fungal plant pathogen, giving us a better understanding of the evolutionary history of the pathogen itself.
Meta-analysis of the Effect of Orlistat on The Body Mass Index in Obese Subjects
Authors: Jeong Gyeonghwa , Han Dongwoo , Ahmed Mahmoud , Kim Deok Ryong
Published: November 2022

Obesity is a widespread health issue worldwide. Therefore, evaluating existing pharmaceuticals and developing new effective strategies to mitigate the problem is essential. Although literature reviews of a broad range of interventions for managing obesity exist, a recent evaluation of the efficacy of orlistat is lacking. This meta-analysis aims to quantify the efficacy of orlistat on body mass index (BMI) and the impact of age, dose, duration, and comorbidities. A literature search of orlistat on PubMed was carried out, and 177 placebo-controlled randomized clinical trials published in the last twenty years were identified. Sixteen studies that met the inclusion criteria were selected for further analysis. Two investigators independently extracted data from the clinical reports using a predefined protocol. We conducted a meta-analysis using random and mixed effects models with different moderators. We found that, on aggregate, the orlistat group reduced their BMI by 0.72 kg/m2(P< 0.05) compared to the placebo group. In addition, a longer duration of intervention led to a greater decrease in BMI. Moreover, patients with comorbidities experienced a smaller change in BMI. In conclusion, the evidence suggests that orlistat moderately reduces BMI in obese subjects. The effect of lifestyle modifications, side effects, and drug interactions should be assessed in future studies.
Characterization of yield and fruit quality parameters of Vietnamese elite tomato lines generated through phenotypic selection and conventional breeding methods
Authors: Nguyen Cam Chau , Shelake Rahul Mahadev , Van Tien Vu , Van Hai Tong , Thi Nhan Nguyen , Nguyen Xuan Canh , Do Vo-Anh-Khoa , Thanh Hai Nguyen , Kim Jae-Yean
Published: November 2022

Tomato (Solanum lycopersicumL.) is the second most important vegetable crop after potatoes, and global demands have been steadily increasing in recent years. Conventional breeding has been applied to breed and domesticate tomato varieties to meet the need for higher yield or superior agronomical traits that allow to sustain under different climatic conditions. In the current study, we applied bulk population breeding by crossing eight tomato accessions procured from the Asian Vegetable Research and Development Center (AVRDC) with three heat-resistant tomato inbred lines from Vietnam and generated ten elite tomato (ET) lines in the F8 generation. The individual F8 lines exhibited robust vigor and adaptability to Vietnamese climate conditions. Among the ten lines, ET1 and ET3 displayed indeterminate growth. ET2 showed semi-determinate, while all the other lines had determinate growth. The different ET lines showed distinctive superior agronomical traits, including early maturing (ET4, ET7, and ET10), highly efficient fruit set (ET1), higher yield (ET1, ET8, ET10), jointless pedicels (ET2), and partial parthenocarpy (ET9). Molecular analysis revealed that the ET3 line consisted ofTy-1andTy-3loci that positively contribute toTomato yellow leaf curl virus(TYCLV) resistance in tomato plants. The elite tomato lines developed in this study would contribute significantly to the Vietnamese and Asian gene pool for improved tomato production and may be a valuable resource for various breeding goals.
Genomic consequences of range expansion and colonisation in the reed warbler (Acrocephalus scirpaceus)
Authors: Sætre Camilla Lo Cascio , Rönkä Katja , Ravinet Mark , Vitulano Severino , Caldarella Matteo , Procházka Petr , Stokke Bård , Cuevas Angélica , Bergman Nora , Thorogood Rose , Jakobsen Kjetill S. , Tørresen Ole K. , Eroukhmanoff Fabrice
Published: November 2022

Range expansion is a common natural phenomenon, which may be intensified by human-induced drivers such as climate change and alterations of habitat. The genetic consequences of range expansion are potentially major, and it is important to study known cases of range expansion to understand how human activities affect contemporary evolution, and to learn more about the genetic adaptive potential of species. The reed warbler (Acrocephalus scirpaceus) is a long-distance migratory bird breeding in Eurasia and wintering south of Sahara. It is currently expanding its range northwards, likely as a consequence of climate change. Interestingly, however, reed warblers have also recently colonised new territory southwards, following habitat restoration at the southern range margin. In this study, we investigate the genetic consequences of these two-directional range expansions with RAD-seq, looking at 10 populations from north to south in Europe. We investigate population structure and genome diversity, and assess the role of selection in divergence between populations across the species range. We do not find evidence of strong genetic structure in the reed warbler populations, and the youngest edge populations do not exhibit any substantial loss in genetic diversity, suggesting ongoing gene flow. On a smaller scale, the edge populations are the most genetically distinct, and we identify environmental disparity, especially in precipitation variability, as the main barrier of gene flow, to a greater extent than geographic distance. We find no evidence that the loci involved in population divergence and adaptation in the core populations are the same that are involved in adaptation at the range edges. Using three genome scan methods to identify selection, we found 49 SNPs putatively under selection, of which 33 were located in introns of 28 unique genes. Most of these are correlated with differences in climatic variables of temperature and precipitation. Some genome scan outliers show signs of being part of nascent selective sweeps, especially one which is distinct for the northern range edge. Our results suggest that in the reed warbler, contemporary range expansion has had little effect on molecular diversity and has been rapidly followed by local adaptation to climatic conditions, which could further corroborate the rapid pace at which colonisation of novel environments has occurred both northwards and southwards.