bluuebunny/crossref_metadata_2025 huggingface dataset:
Aquatic Exercise and Its Effect on Participation, Quality of Life, and Falls Self-efficacy in Older Adults: A Pilot Study
Authors: Michaels Natalie Norman , Espiritu Elena Wong , Broecker Megan , Gonyea Stephanie , Hendricks Tori , McClintock Kelli , Sanders Katherine , Stelbasky Danielle
Published: May 2022

Background:

Falls are extremely common in the older adult population, and fear of falling has been cited as one of the main reasons older adults may choose not to participate in social activities. Exercising in the water can provide support from buoyancy that helps reduce this fear, leading to increased participation in meaningful activities.

Purpose:

The purpose of this mixed-methods research study was to determine whether participation in an aquatic exercise program was an effective way to increase falls self-efficacy, social participation, and quality of life in older adults.

Methods:

Twelve adults, aged 62 to 77 years, participated in 1-hour aquatic exercise sessions, twice per week for 4 weeks. Participants completed a demographic questionnaire, and 3 pre/posttest measures: the Keele Assessment of Participation (Keele), the Falls Efficacy Scale-International (FES-I) for falls self-efficacy, and the World Health Organization's Quality of Life Scale (WHOQOL-BREF) for quality of life. They also completed an expectations check sheet and one open-ended question asking about the meaning and effect of the program.

Results:

Although there were no significant differences found between pre/posttest scores on the Keele, there was a statistically significant difference in reported falls self-efficacy with respect to ability to climb and descend stairs (P = .046). There was also a statistically significant difference on the WHOQOL-BREF for access to available information (P = .025) and for participant satisfaction with ability in performing activities of daily living (P = .046), as well as a significant increase in the number of anticipated benefits versus the number of gained benefits (P = .032). Qualitatively, participants reported improved body functions, increased social interactions, and experiencing enjoyment and motivation with the change in activity. Relevance: Participation in aquatic exercise may have positive effects on falls self-efficacy, social participation, and quality of life in older adults. This was a small sample size, however, and further research is recommended.
Association Between Trait Energy and Fatigue and Aquatic Functional Tests: An Exploratory Study
Authors: Boolani Ali , Allen Amy , Barrios Nathalie , Sames Carol
Published: May 2022

Background:

Recent studies have reported energy and fatigue as two separate moods. Interestingly, a recent study reported associations between over-ground functional assessments scores in older adults and feelings of energy, but no significant association between functional status and feelings of fatigue.

Purpose:

The purpose of this exploratory study is to assess an association between trait mental and physical energy and fatigue and functional assessments in an aquatic setting.

Methodlogy:

Participants (n=16) in a community aquatic exercise program completed a series of functional assessments; 30-second aquatic sit-to-stand, 7.64-m aquatic walk, and 6-minute walk (6MWT). Assessments for the participants were performed on the first day of aquatics exercise and every 12 weeks thereafter between September 2019 and March 2020. Trait mental and physical energy and fatigue were measured prior to the assessments using the Mental and Physical State and Trait Energy and Fatigue Scales. Using a Wilcoxon rank test, we determined that there were no significant differences between the baseline and 12-week assessments for all trait moods and all functional assessments. Using the Spearman's rho bivariate correlation, we determined that those who reported a higher trait physical energy walked further during the 6MWT and completed the 7.64-m walk quicker.

Results:

Our findings indicate that the relationship between feelings of physical energy and functional status is also true in an aquatic setting.

Conclusion:

Clinicians can utilize the findings of our study to design holistic programs that may increase functional status and feelings of physical energy in populations of adults with chronic diseases.
Research Report: Efficacy and Safety of a Novel Aquatic Device for Children With Postural Dysfunction
Authors: Breighner Joshua , Saavedra Sandra , Snowdon Donna
Published: May 2022

Background and Purpose:

Children with postural dysfunction often enjoy aquatic activities but are limited in their ability to play and interact in the water due to limited motor control and safety concerns. The purpose of this study was to explore the benefits of postural contexts provided by a novel aquatic device (Water Strider) in children with postural dysfunction. Providing stable vertical support is hypothesized to improve overall environmental interactions/social engagement and increase safety, autonomy, and motivation for movement (kicking and reaching).

Methods:

The proposed device provided external support that could be modified on the basis of user-specific level of head and trunk control. Feasibility, safety, and efficacy of the device were tested for 9 children (aged 2-8 years) with postural dysfunction (7 with cerebral palsy). For this purpose, a 10-minute aquatic trial for baseline aquatic activities along with use of the Water Strider was performed for comparison with video behavior coding to quantify arm and leg movements, assistance, and hazardous events (water in eyes or water in mouth).

Results:

Total assistance required significantly decreased from baseline (100%) to the Water Strider (21%; F
1,8 = 384.4, P ≤ .001), and significantly fewer instances where children were found to have water in their mouth occurred across all participants (baseline: 12 events; Water Strider: 0 events). Significant increase in total leg movement/reciprocal kicking (F
1,8 = 8.84, P < .001; F
1,8 = 11.1, P = .003) and decrease in arm movements (F
1,8 = 0.036, P < .001) with relation to the level of trunk control were also observed.
Towards a system-level causative knowledge of pollinator communities
Authors: Saavedra Serguei , Bartomeus Ignasi , Godoy Oscar , Rohr Rudolf P. , Zu Penguan
Published: May 2022

Pollination plays a central role in both crop production and maintaining biodiversity. However, habitat loss, pesticides, invasive species and larger environmental fluctuations are contributing to a dramatic decline of pollinators worldwide. Different management solutions require knowledge of how ecological communities will respond following interventions. Yet, anticipating the response of these systems to interventions remains extremely challenging due to the unpredictable nature of ecological communities, whose nonlinear behaviour depends on the specific details of species interactions and the various unknown or unmeasured confounding factors. Here, we propose that this knowledge can be derived by following a probabilistic systems analysis rooted on non-parametric causal inference. The main outcome of this analysis is to estimate the extent to which a hypothesized cause can increase or decrease the probability that a given effect happens without making assumptions about the form of the cause–effect relationship. We discuss a road map for how this analysis can be accomplished with the aim of increasing our system-level causative knowledge of natural communities.

This article is part of the theme issue ‘Natural processes influencing pollinator health: from chemistry to landscapes’.
Pollinator selection against toxic nectar as a key facilitator of a plant invasion
Authors: Egan Paul A. , Stevenson Philip C. , Stout Jane C.
Published: May 2022

Plant compounds associated with herbivore defence occur widely in floral nectar and can impact pollinator health. We showed previously thatRhododendron ponticumnectar contains grayanotoxin I (GTX I) at concentrations that are lethal or sublethal to honeybees and a solitary bee in the plant's non-native range in Ireland. Here we further examined this conflict and tested the hypotheses that nectar GTX I is subject to negative pollinator-mediated selection in the non-native range, but that phenotypic linkage between GTX I levels in nectar and leaves acts as a constraint on independent evolution. We found that nectar GTX I experienced negative directional selection in the non-native range, in contrast to the native Iberian range, and that the magnitude and frequency of pollinator limitation indicated that selection was pollinator-mediated. Surprisingly, nectar GTX I levels were decoupled from those of leaves in the non-native range, which may have assisted post-invasion evolution of nectar without compromising the anti-herbivore function of GTX I (here demonstrated in bioassays with an ecologically relevant herbivore). Our study emphasizes the centrality of pollinator health as a concept linked to the invasion process, and how post-invasion evolution can be targeted toward minimizing lethal or sub-lethal effects on pollinators.

This article is part of the theme issue ‘Natural processes influencing pollinator health: from chemistry to landscapes’.
Atlantic Cod as an indicator of rapid climate change
Authors: Choi Jae S.
Published: May 2022

Atlantic cod (Gadus morhua) in the northwest Atlantic has become the textbook example of overfishing. However, this narrative has blinded us from the larger environmental context of this decline. Cod prefer cold and shallow habitats, environments that are also the most susceptible to rapid climate change. Cod habitat deterioration was evident well before their numerical decline, and as such, cod was a harbinger of rapid climate change. Recovery requires their habitat quality to first improve and stabilize. Calls for a cull of seals, the consensus actor causing the lack of recovery of cod, may therefore be unwise. Recovery will only occur once the variability associated with rapid climate change subsides and habitat quality improves. The timeline for this is of course unknown.

One-Sentence Summary

Was the decline of cod a harbinger of rapid climate change in the northwest Atlantic?
The arthropod associates of 155 North American cynipid oak galls
Authors: Ward Anna K.G. , Busbee Robert W. , Chen Rachel A. , Davis Charles K. , Driscoe Amanda L. , Egan Scott P. , Goldberg Bailey A.R. , Hood Glen Ray , Jones Dylan G. , Kranz Adam J. , Meadely Dunphy Shannon A. , Milks Alyson K. , Ott James R. , Prior Kirsten M. , Sheikh Sofia I. , Shzu Shihan , Weinersmith Kelly L. , Zhang Linyi , Zhang Y. Miles , Forbes Andrew A.
Published: May 2022

The identities of most arthropod associates of cynipid-induced oak galls in the western Palearctic are generally known. However, a comprehensive accounting of associates has been performed for only a small number of the galls induced by the estimated 700 species of cynipid gall wasp in the Nearctic. This gap in knowledge stymies many potential studies of diversity, coevolution, and community ecology, for which oak gall systems are otherwise ideal models. We report rearing records of insects and other arthropods from more than 527,306 individual galls representing 201 different oak gall types collected from 32 oak tree species in North America. Of the 201 gall types collected, 155 produced one or more animals. A total of 151,075 animals were found in association with these 155 gall types, and of these 61,044 (40.4%) were gall wasps while 90,031 (59.6%) were other arthropods. We identified all animals to superfamily, family, or, where possible, to genus. We provide raw numbers and summaries of collections, alongside notes on natural history, ecology, and previously published associations for each taxon. For eight common gall-associated genera (Synergus,Ceroptres,Euceroptres,Ormyrus,Torymus,Eurytoma,Sycophila, andEuderus), we also connect rearing records to gall wasp phylogeny, geography, and ecology - including host tree and gall location (host organ), and their co-occurrence with other insect genera. Though the diversity of gall wasps and the large size of these communities is such that many Nearctic oak gall-associated insects still remain undescribed, this large collection and identification effort should facilitate the testing of new and varied ecological and evolutionary hypotheses in Nearctic oak galls.
Clinical Features and Outcomes of COVID-19 at a Teaching Hospital in Kingston, Jamaica
Authors: Thompson Tamara , Dawkins Yvonne , Rowe-Gardener Swane , Chin-Harty Lisa , Hoe Kyaw Kyaw , Ferguson Trevor S. , Ehikhametalor Kelvin , Gordon-Johnson Kelly Ann , Deyde Varough
Published: May 2022

Objective

We examined the demographic, clinical characteristics and indicators of poor outcomes among hospitalized adults with COVID-19 at the University Hospital of the West Indies, Jamaica.

Methods

A retrospective medical record review between March 10 and December 31, 2020 analyzed data for 362 participants.

Results

There were 218 males (mean age 59.5 years) and 144 females (mean age 55.7 years). Hypertension, diabetes mellitus, cardiovascular disease, obesity and chronic kidney disease were the most common comorbidities. Cough, shortness of breath, fever and malaise were the most common presenting complaints. Fifty-one percent of patients were moderately to severely ill on admission; 11% were critically ill; 18% were admitted to the Intensive Care Unit (ICU). Death occurred in 62 (17%) patients (95% CI 13.6-21.4%). Among obese participants, there were increased odds of developing respiratory failure (OR 5.2, p < 0.001), acute kidney injury (OR 4.7, p < 0.001), sepsis (OR 2.9, p =0.013) and the need for ICU care (OR 3.7, p < 0.001). Factors independently associated with increased odds of death were age (OR 1.03 per year, p = 0.013) and obesity (OR 2.26, p = 0.017). Mortality also correlated significantly with D-dimer > 1000 ng/ml (OR 2.78; p = 0.03), serum albumin < 40 g/L (OR 3.54; p = 0.03) and serum LDH > 485 U/L OR 1.92, p = 0.11).

Conclusions

Targeted interventions among these high-risk patient subgroups may reduce in-patient morbidity and mortality.
Cognitive improvement after dual-task training in Parkinson’s disease: a follow-up study
Authors: Szögedi Dalma , Stone Trevor W. , Dinya Elek , Málly Judit
Published: May 2022

The reaction times of patients with Parkinson’s disease (PD) in tests of simultaneous dual-task accuracy are dependent on the subjects’ cognitive ability. We now report that one week training on dual-task tests improved cognitive function. Forty-six PD patients were compared with 47 age matched healthy controls and 26 patients were followed for one year. Five dual-task tests consisting of a primary cognitive task to be performed simultaneously with a secondary motor task were repeated for five consecutive days. Testing was repeated after 6 and 12 months. Participants’ reaction times, including Hits and Misses, were quantified. Initial tests indicated slower reaction times in patients compared to controls, with fewer Hits and more Misses, especially in PD patients over 65 years of age. Training by daily repeated dual-task tests improved performance within 3 days (p < 0. 01 or p < 0.001), with no deterioration after 6 months. We conclude that dual-tasks are objective and sensitive tests for detecting early cognitive difficulties in PD, with improvements in both by repeated exposure to testing. A few days of testing produced cognitive improvement lasting many months. It is recommended that the use of simultaneous, dual-task testing is used to produce long-lasting improvement of cognitive function in PD patients.
Quantitative environmental DNA metabarcoding shows high potential as a novel approach to quantitatively assess fish community
Authors: Tsuji Satsuki , Inui Ryutei , Nakao Ryohei , Miyazono Seiji , Saito Minoru , Kono Takanori , Akamatsu Yoshihisa
Published: May 2022

The simultaneous conservation of species richness and evenness is important to effectively reduce biodiversity loss and keep ecosystem health. Environmental DNA (eDNA) metabarcoding has been used as a powerful tool for identifying community composition, but it does not necessarily provide quantitative information due to several methodological limitations. Thus, the quantification of eDNA through metabarcoding is an important frontier of eDNA-based biomonitoring. Particularly, the qMiSeq approach has recently been developed as a quantitative metabarcoding method and has attracted much attention due to its usefulness. The aim here was to evaluate the performance of the qMiSeq approach as a quantitative monitoring tool for fish communities by comparing the quantified eDNA concentrations with the results of fish capture surveys. The eDNA water sampling and the capture surveys using the electrical shocker were conducted at a total of 21 sites in four rivers in Japan. As a result, we found significant positive relationships between eDNA concentrations of each species quantified by qMiSeq and both the abundance and biomass of each captured taxon at each site. Furthermore, for seven out of eleven taxa, a significant positive relationship was observed between quantified DNA concentrations by sample and the abundance and/or biomass. In total, our results demonstrated that eDNA metabarcoding with the qMiSeq approach is a suitable and useful tool for quantitative monitoring of fish communities. Due to the simplicity of the eDNA analysis, the eDNA metabarcoding with qMiSeq approach would promote further growth of quantitative monitoring of biodiversity.

Highlights

eDNA analysis and capture surveys of fishes were conducted at a total of 21 sites.

Quantitative eDNA metabarcoding (qMiSeq) successfully quantified the eDNA of fishes.

For each site, the estimated eDNA conc. reflected the abundance and biomass of fishes.

For each taxon, the estimated eDNA conc. were comparable among sites.

qMiSeq is a suitable and useful tool for quantitative monitoring of fish community.
CLARITY increases sensitivity and specificity of fluorescence immunostaining in long-term archived human brain tissue
Authors: Woelfle Sarah , Deshpande Dhruva , Feldengut Simone , Roselli Francesco , Deisseroth Karl , Michaelis Jens , Boeckers Tobias M. , Schön Michael
Published: May 2022

Immunohistochemistry on archival human brains is often limited because several conditions arise that complicate the use for high-resolution fluorescence microscopy. In this study, we developed a novel clearing approach for immunofluorescence-based analysis of perfusion- and immersion-fixed post mortem human brain tissue, termed hCLARITY. hCLARITY is optimized for specificity by reducing off-target labeling and yields very sensitive stainings in human brain sections allowing for super-resolution microscopy with unprecedented imaging of pre- and postsynaptic compartments. Moreover, hallmarks of the Alzheimer’s disease were preserved with hCLARITY, and importantly classical DAB or Nissl stainings are compatible with this protocol. hCLARITY is extremely versatile as demonstrated by the use of more than 30 well performing antibodies and allows for de- and subsequent re-staining of the same tissue section, which is important for multi-labelling approaches, e.g., in super-resolution microscopy. Taken together, hCLARITY enables research of the human brain with highest sensitivity and down to sub-diffraction resolution and therefore has enormous potential for the investigation of local morphological changes, e.g., in neurodegenerative diseases.

Striking Image / Graphical abstract

Summary of the main advantages of hCLARITY. CLARITY was applied on human post mortem brain tissue in direct comparison to untreated sections (minus CLARITY). Owing to removal of lipids during the clearing with SDS and the resulting reduction in light scattering, cleared sections were less opaque. The denaturing effect of the detergent SDS most likely results in better accessibility of certain epitopes. The major benefits of hCLARITY were found in an increased sensitivity and specificity of antibodies for neuronal cells. The adapted hCLARITY protocol is compatible with staining techniques for confocal microscopy, super-resolution microscopy, and light microscopy.
Stem cell heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafish
Authors: Frantz William Tyler , Iyengar Sharanya , Neiswender James , Cousineau Alyssa , Maehr Rene , Ceol Craig J.
Published: May 2022

Tissue-resident stem cells are present in many adult organs, where they are important for organ homeostasis and repair in response to injury. However, the signals that activate these cells and the mechanisms governing how these cells self-renew or differentiate are highly context-dependent and incompletely understood, particularly in non-hematopoietic tissues. In the skin, melanocyte stem cells (McSCs) are responsible for replenishing mature pigmented melanocytes. In mammals, these cells reside in the hair follicle bulge and bulb niches where they are activated during homeostatic hair follicle turnover and following melanocyte destruction, as occurs in vitiligo and other skin hypopigmentation disorders. Recently, we identified adult McSCs in the zebrafish. To elucidate mechanisms governing McSC self-renewal and differentiation we analyzed individual transcriptomes from thousands of melanocyte lineage cells during the regeneration process. We identified transcriptional signatures for McSCs, deciphered transcriptional changes and intermediate cell states during regeneration, and analyzed cell-cell signaling changes to discover mechanisms governing melanocyte regeneration. We identified KIT signaling via the RAS/MAPK pathway as a regulator of McSC direct differentiation. Analysis of the scRNAseq dataset also revealed a population of mitfa/aox5 co-expressing cells that divides following melanocyte destruction, likely corresponding to cells that undergo self-renewal. Our findings show how activation of different subpopulations of mitfa-positive cells underlies self-renewal and differentiation to properly reconstitute the melanocyte pigmentary system following injury.
Low mutation load in a supergene underpinning alternative male mating strategies in ruff
Authors: Hill Jason , Enbody Erik , Bi Huijuan , Lamichhaney Sangeet , Schwochow Doreen , Younis Shady , Widemo Fredrik , Andersson Leif
Published: May 2022

Ruffs are shorebirds with an elaborate lekking behavior involving three male morphs with different mating strategies: Independents, Satellites, and Faeders1,2. The latter two are heterozygous for different versions of a supergene maintained by an inversion that were estimated to have occurred about 4 million years ago3. Faeders carry an intact inversion while the Satellite allele is recombinant, both of which are expected to accumulate high mutational load because they are recessive lethals. Here we have constructed a highly contiguous genome assembly of the inversion region for both the Independent and Satellite haplotypes. The recombination event(s) between an inverted and non-inverted chromosome creating the Satellite allele must have occurred recently (within the last 100,000 years) based on the minute sequence divergence between the Satellite and Independent alleles in the recombinant regions. Contrary to expectations4,5, we find no expansion of repeats and only a very modest mutation load on the Satellite allele in the nonrecombinant region despite high sequence divergence (1.46%). The essential centromere protein CENPN gene is disrupted by the inversion, and surprisingly is as well conserved on the inversion haplotypes as on the noninversion haplotype. The results suggest that the inversion may be much younger than previously thought. The lack of mutation load despite recessive lethality can be explained by the introgression of the inversion from a now extinct lineage.
Powdery mildew effectors AVRA1and BEC1016 target the ER J-domain proteinHvERdj3B required for immunity in barley
Authors: Li Zizhang , Velásquez-Zapata Valeria , Elmore J. Mitch , Li Xuan , Xie Wenjun , Deb Sohini , Tian Xiao , Banerjee Sagnik , Jørgensen Hans J. L. , Pedersen Carsten , Wise Roger P. , Thordal-Christensen Hans
Published: May 2022

The barley powdery mildew fungus,Blumeria hordei(Bh), secretes hundreds of candidate secreted effector proteins (CSEPs) to facilitate pathogen infection and colonization. One of these, CSEP0008, is directly recognized by the barley nucleotide-binding leucine-rich-repeat (NLR) receptor, MLA1, and therefore designated AVRA1. Here we show that AVRA1and the sequence-unrelatedBheffector BEC1016 (CSEP0491) suppress immunity in barley. We used yeast two-hybrid next-generation interaction screens (Y2H-NGIS), followed by binary Y2H andin plantaprotein-protein interactions studies, and identified a common barley target of AVRA1and BEC1016, the endoplasmic reticulum (ER)-localized J-domain protein,HvERdj3B. Silencing of this ER quality control (ERQC) protein increased theBhpenetration.HvERdj3B is ER luminal, and we showed using split GFP that AVRA1and BEC1016 translocate into the ER - signal peptide-independently. Silencing ofHvERdj3B and expression the two effectors hampered trafficking of a vacuolar marker through the ER as a shared cellular phenotype, agreeing with the effectors targeting this ERQC component. Together, these results suggest that the barley innate immunity, preventingBhentry into epidermal cells, is dependent on ERQC, which in turn requires the J-domain protein,HvERdj3B, regulated by AVRA1and BEC1016. Plant disease resistance often occurs upon direct or indirect recognition of pathogen effectors by host NLR receptors. Previous work has shown that AVRA1is directly recognized in the cytosol by the immune receptor, MLA1. We speculate that the AVRA1J-domain target being inside the ER, where it is inapproachable by NLRs, has forced the plant to evolve this challenging direct recognition.

SIGNIFICANCE

The complex plant immune system is highly dependent on fundamental cellular machineries, such as the endomembrane system and the ER quality control (ERQC), essential for delivery of immunity-associated membrane-bound and endomembrane soluble proteins to their destinations. We now find that pathogen effectors can interact with an ERQC component and suppress immunity, thereby adding to the molecular insight in plant-pathogen interactions.
FASTAptameR 2.0: A Web Tool for Combinatorial Sequence Selections
Authors: Kramer Skyler T. , Gruenke Paige R. , Alam Khalid K. , Xu Dong , Burke Donald H.
Published: May 2022

Combinatorial selections are powerful strategies for identifying biopolymers with specific biological, biomedical, or chemical characteristics. Unfortunately, most available software tools for high-throughput sequencing analysis have high entrance barriers for many users because they require extensive programming expertise. FASTAptameR 2.0 is an R-based reimplementation of FASTAptamer designed to minimize this barrier while maintaining the ability to answer complex sequence-level and population-level questions. This opensource toolkit features a user-friendly web tool, interactive graphics, up to 100x faster clustering, an expanded module set, and an extensive user guide. FASTAptameR 2.0 accepts diverse input polymer types and can be applied to any sequence-encoded selection.
Floral humidity as a signal – not a cue – in a nocturnal pollination system
Authors: Dahake Ajinkya , Jain Piyush , Vogt Caleb , Kandalaft William , Stroock Abraham , Raguso Robert A.
Published: May 2022

Although visual and olfactory floral signals attract pollinators from a distance, at the flower’s threshold, pollinators can use floral humidity as an index cue for nectar presence. We evaluate the role of floral humidity in theDatura wrightii-Manduca sextanocturnal pollination system. In addition to our finding thatM. sextashows strong innate attraction toward humid flowers, we identify the hygrosensing sensillum on their antennae, demonstrate its extreme sensitivity to minute changes in RH, and observe the elimination of moths’ behavioral preference towards humid flowers following experimental occlusion of the sensilla. Despite Manduca’s attraction toward humid flowers, we find that floral humidity is not a reliable cue for nectar presence in this system. While Datura floral headspace sustains an enormous humidity gradient, it is not a consequence of nectar evaporation, but an outcome of gas exchange through floral stomata and is decoupled from nectar presence. Using interdisciplinary tools, we demonstrate the function of floral humidity as an attractive signal, not a cue, in this pollination system, thus showcasing an underappreciated modality by which flowers may manipulate their visitors.
UniTVelo: temporally unified RNA velocity reinforces single-cell trajectory inference
Authors: Gao Mingze , Qiao Chen , Huang Yuanhua
Published: May 2022

The recent breakthrough of single-cell RNA velocity methods brings attractive promises to reveal directed trajectory on cell differentiation, states transition and response to perturbations. However, the existing RNA velocity methods are often found to return erroneous results, partly due to model violation or lack of temporal regularization. Here, we present UniTVelo, a statistical framework of RNA velocity that models the dynamics of spliced and unspliced RNAs via flexible transcription activities. Uniquely, it also supports the inference of a unified latent time across the transcriptome. With ten datasets, we demonstrate that UniTVelo returns the expected trajectory in different biological systems, including hematopoietic differentiation and those even with weak kinetics or complex branches.
The lateral habenula mediates the association of a conditioned stimulus with the absence of an appetitive unconditioned stimulus
Authors: Kim Dong-Hee , Jin In-Beom , Kim Nam-Heon , Jeon Yong-Jae , Choi Bo-Ryoung , Gallagher Michela , Han Jung-Soo
Published: May 2022

The lateral habenula (LHb) has been implicated in conditioned inhibition. Here, the modulating effects of LHb activity on the association of a conditioned stimulus (CS) with the nonoccurrence of an unconditioned stimulus (US) were assessed in vivo using chemogenetic methods. Animals initially received explicitly unpaired CS light and US food presentations. Animals subjected to a retardation-of-acquisition task subsequently underwent light and food pairings, whereas those subjected to a summation task underwent compound light-tone and food pairings. The inhibitory light strength was assessed based on retardation of the acquisition of food-cup conditioned responses (CRs) in light-food pairings and comparisons of food-cup CRs to each stimulus in a CS-alone test following compound training. Neurotoxic LHb lesions and chemogenetic LHb inhibition throughout unpaired training attenuated the inhibitory light strength. Furthermore, chemogenetic LHb activation accelerated the decline in CR induced by repeated light-alone presentations following light-food pairings. Therefore, the LHb critically contributes to conditioned inhibition.
scTopoGAN: unsupervised manifold alignment of single-cell data
Authors: Singh Akash , Reinders Marcel J.T. , Mahfouz Ahmed , Abdelaal Tamim
Published: May 2022

Motivation

Single-cell technologies allow deep characterization of different molecular aspects of cells. Integrating these modalities provides a comprehensive view of cellular identity. Current integration methods rely on overlapping features or cells to link datasets measuring different modalities, limiting their application to experiments where different molecular layers are profiled in different subsets of cells.

Results

We present scTopoGAN, a method for unsupervised manifold alignment of single-cell datasets with non-overlapping cells or features. We use topological autoencoders to obtain latent representations of each modality separately. A topology-guided Generative Adversarial Network then aligns these latent representations into a common space. We show that scTopoGAN outperforms state-of-the-art manifold alignment methods in complete unsupervised settings. Interestingly, the topological autoencoder for individual modalities also showed better performance in preserving the original structure of the data in the low-dimensional representations when compared to other manifold projection methods. Taken together, we show that the concept of topology preservation might be a powerful tool to align multiple single modality datasets, unleashing the potential of multi-omic interpretations of cells.

Availability and implementation

Implementation available on GitHub (https://github.com/AkashCiel/scTopoGAN). All datasets used in this study are publicly available.

Contact

t.r.m.abdelaal@lumc.nl
Ultrasonic Artificial Intelligence Shows Statistically Equivalent Performance for Thyroid Nodule Diagnosis to Fine Needle Aspiration Cytopathology and BRAFV600E Mutation Analysis Combined
Authors: Zhou Tianhan , Xu Lei , Shi Jingjing , Zhang Yu , Hu Tao , Xu Rujun , Xie Lesi , Sun Lijuan , Li Dandan , Zhang Wenhua , Chen Chuanghua , Wang Wei , Xu Chenke , Kong Fanlei , Xun Yanping , Yu Lingying , Zhang Shirong , Ding Jinwang , Wu Fan , Tang Tian , Zhan Siqi , Zhang Jiaoping , Kong Dexing , Luo Dingcun
Published: May 2022

Objective

To investigate the difference between an artificial intelligence (AI) system, fine-needle aspiration (FNA) cytopathology, BRAFV600E mutation analysis and combined method of the latter two in thyroid nodule diagnosis.

Methods

Ultrasound images of 490 thyroid nodules (378 patients) with postsurgical pathology or twice of consistent combined FNA examination outcomes with a half-year interval, which were considered as gold standard, were collected and analyzed. The diagnostic efficacies of an AI diagnostic system and FNA-based methods were evaluated in terms of sensitivity, specificity, accuracy, κ coefficient compared to the gold standard.

Results

The malignancy threshold of 0.53 for an AI system was selected according to the optimization of Youden index based on a retrospective cohort of 346 nodules and then applied for a prospective cohort of 144 nodules. The combined method of FNA cytopathology according to Bethesda risk stratification system and BRAFV600E mutation analysis showed no significant difference in comparison with the AI diagnostic system in accuracy for both the retrospective and prospective cohort in our single center study. Besides, for the 33 indeterministic Bethesda system category III and IV nodules included in our study, the AI system showed no significant difference in comparison with the BRAFV600E mutation analysis.

Conclusion

The evaluated AI diagnostic system showed similar diagnostic performance to FNA cytopathology combined with and BRAFV600E mutation analysis. Given its advantages in ease of operation, time efficiency, and noninvasiveness for thyroid nodule screening as well as the wide availability of ultrasonography, it can be widely applied in all levels of hospitals and clinics to assist radiologists for thyroid nodule diagnosis and is expected to reduce the need for relatively invasive FNA biopsies and thereby reducing the associated risks and side effects as well as to shorten the diagnostic time.
Acute exercise induces natural killer cell mobilization but not infiltration into prostate cancer tissue in humans
Authors: Schenk A , Esser T , Belen S , Gunasekara N , Joisten N , Winker M , Weike L , Bloch W , Heidenreich A , Herden J , Löser H , Oganesian S , Theurich S , Watzl C , Zimmer P
Published: May 2022

The mobilization and activation of natural killer (NK) cells have been proposed as key mechanisms promoting anti oncogenic effects of physical exercise. Although mouse models have proven that physical exercise recruits NK cells to tumor tissue and inhibits tumor growth, this preclinical finding has not been transferred to the clinical setting yet. In this first-in-human study, we found that physical exercise mobilizes and redistributes NK cells, especially those with a cytotoxic phenotype, in line with preclinical models. However, physical exercise did not increase NK cell tumor infiltrates. Future studies should carefully distinguish between acute and chronic exercise modalities and should be encouraged to investigate more immune responsive tumor entities.
Artificial Intelligence Enables Quantitative Assessment of Ulcerative Colitis Histology
Authors: Najdawi Fedaa , Sucipto Kathleen , Mistry Pratik , Hennek Stephanie , Jayson Christina , Lin Mary , Fahy Darren , Kinsey Shawn , Wapinski Ilan , Beck Andrew H. , Resnick Murray B. , Khosla Archit , Drage Michael G.
Published: May 2022

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is characterized by a relapsing and remitting course. Appropriate assessment of disease activity is critical for adequate treatment decisions. In addition to endoscopic mucosal healing, histologic remission is emerging as a treatment target and a key factor in the evaluation of disease activity and therapeutic efficacy. However, there is no standardized definition of histologic remission, limiting the utility of histologic scoring, and manual pathologist evaluation is subject to intra-and inter-observer variability. Machine learning approaches are increasingly being developed to aid pathologists in accurate and reproducible scoring of histology, and can enable sensitive assessment of clinically relevant features. Here we report a proof-of-concept study using the PathAI platform to develop ML models for identification and quantification of UC histological features directly from hematoxylin and eosin (H&E)-stained whole slide images. Model-predicted histological features were used to quantify tissue area proportions and cell count proportions and densities, which correlated with disease severity and pathologist-assigned Nancy Histological Index (NHI) scores. Moreover, using multivariate analysis based on selected model-predicted histological features, we were able to accurately predict NHI scores, with a weighted kappa (k=0.93) and Spearman correlation (ρ=0.93, p<0.001) when compared to manual pathologist consensus NHI scores. We were also able to predict histological remission, based on the resolution of active inflammation, with high accuracy of 0.94. These results demonstrate the accuracy of ML models in quantifying histologic features of UC and predicting NHI scores, and highlight the potential of this approach to enable standardized and robust assessment of histologic remission for improved evaluation of disease activity and prognosis.
Differences in epidemiology of enteropathogens in children pre- and post-rotavirus vaccine introduction in Kilifi, coastal Kenya
Authors: Agoti Charles N. , Curran Martin D. , Murunga Nickson , Ngari Moses , Muthumbi Ester , Lambisia Arnold , Frost Simon DW , Blacklaws Barbara , Nokes D. James , Drumright Lydia N
Published: May 2022

Background

In July 2014, Kenya introduced the Rotarix® vaccine into its national immunization program. The impact of this vaccination programme on the local epidemiology of enteropathogens is unclear.

Methods

The TaqMan Array Card (TAC) was used for screening for 28 different enteropathogens in 718 stools from children less than 13 years of age who presented with diarrhea and were admitted to Kilifi County Hospital, coastal Kenya, in 2013 (before vaccine introduction) and in 2016-2018 (after vaccine introduction). The differences between pre- and post-Rotarix® vaccination periods were examined using univariate and multivariable logistic regressions.

Results

In 665 specimens (92.6%), one or more enteropathogens were detected, while in 323 specimens (48.6%), three or more enteropathogens were detected. There was a significant increase in the proportion of samples containing enteroaggregative Escherichia coli (35.7% vs 45.3%, p=0.014), cytomegalovirus (4.2% vs 9.9%, p=0.008), Vibrio cholerae (0.0% vs 2.3%, p=0.019), Strongyloides species (0.8% vs 3.6%, p=0.048) and Dientamoeba fragilis (2.1% vs 7.8%, p=0.004) post-vaccine introduction. Sapovirus detection decreased significantly (7.6% vs 4.0%, p=0.030) post-vaccine introduction. The proportion of samples that tested positive for rotavirus group A did not statistically differ between the pre- and post-vaccine periods (27.4% vs. 23.5%, p=0.253).

Conclusions

In this setting, the burden of childhood enteropathogen infection was high both pre- and post-rotavirus vaccination introduction, with some specific changes in the burden of enteropathogens in hospitalized children after rotavirus vaccination introduction.
A Solution to the Kermack and McKendrick Integro-Differential Equations
Authors: Duclos Ted , Reichert Tom
Published: May 2022

In this manuscript, we derive a closed form solution to the full Kermack and McKendrick integro-differential equations (Kermack and McKendrick 1927) which we call the KMES. We demonstrate the veracity of the KMES using independent data from the Covid 19 pandemic and derive many previously unknown and useful analytical expressions for characterizing and managing an epidemic. These include expressions for the viral load, the final size, the effective reproduction number, and the time to the peak in infections. The KMES can also be cast in the form of a step function response to the input of new infections; and that response is the time series of total infections.

Since the publication of Kermack and McKendrick’s seminal paper (1927), thousands of authors have utilized the Susceptible, Infected, and Recovered (SIR) approximations; expressions putatively derived from the integro-differential equations to model epidemic dynamics. Implicit in the use of the SIR approximation are the beliefs that there is no closed form solution to the more complex integro-differential equations, that the approximation adequately reproduces the dynamics of the integro-differential equations, and that herd immunity always exists. However, the KMES demonstrates that the SIR models are not adequate representations of the integro-differential equations, and herd immunity is not guaranteed. We suggest that the KMES obsoletes the need for the SIR approximations; and provides a new level of understanding of epidemic dynamics.
Evidence for the presence and diagnostic utility of SPM in human peripheral blood
Authors: Dalli Jesmond , Gomez Esteban A , Serhan Charles N
Published: May 2022

We thank O’Donnell et al, for their comments on our contribution and are grateful to be afforded this opportunity to formally respond to their critique24.

We are surprised by the author’s assertion relating to the biological relevance of SPM because a simple literature search for related terms such as ‘resolvin’ in PubMed yields an abundance (>1,420 publications) of evidence supporting the potent biological activities and the diagnostic potential of some of these mediators. Several co-authors of the O’Donnell’s et al manuscript, have published on the resolvins and SPMs, including some publications within recent weeks. Importantly, O’Donnell et al, misreport as well as mis-apply criteria for peak identification reported in the Gomez et al, publication which lead to the flawed analysis they performed.

In this response therefore, we provide a step-by-step clarification of the methodologies used in Gomez et al, and a side-by-side comparison of the underlying data to clarify any confusion. We also demonstrate that using the orthogonal criteria discussed by O’Donnell et al, we obtain essentially identical results thus providing additional validation of our techniques and support the conclusions.
Polycomb-lamina antagonism partitions heterochromatin at the nuclear periphery
Authors: Siegenfeld Allison P. , Roseman Shelby A. , Roh Heejin , Lue Nicholas Z. , Wagen Corin C. , Zhou Eric , Johnstone Sarah E. , Aryee Martin J. , Liau Brian B.
Published: May 2022

The genome can be divided into two spatially segregated compartments, A and B,1,2 which broadly partition active and inactive chromatin states, respectively. Constitutive heterochromatin is predominantly located within the B compartment and comprises chromatin that is in close contact with the nuclear lamina.3–5 By contrast, facultative heterochromatin marked by H3K27me3 can span both compartments.2–5 How epigenetic modifications, A/B compartmentalization, and lamina association collectively maintain heterochromatin architecture and function remains unclear.6,7 Here we developed an approach termed Lamina-Inducible Methylation and Hi-C (LIMe-Hi-C) that jointly measures chromosome conformation, DNA methylation, and nuclear lamina positioning. Through this approach, we identified topologically distinct A/B sub-compartments characterized by high levels of H3K27me3 and differing degrees of lamina association. To study the regulation of these sub-compartments, we inhibited Polycomb repressive complex 2 (PRC2), revealing that H3K27me3 is an essential factor in sub-compartment segregation. Unexpectedly, PRC2 inhibition also elicited broad gains in lamina association and constitutive heterochromatin spreading into H3K27me3-marked B sub-compartment regions. Consistent with repositioning to the lamina, genes originally marked with H3K27me3 in the B compartment, but not in the A compartment, remained largely repressed, suggesting that constitutive heterochromatin spreading can compensate for loss of H3K27me3 at a transcriptional level. These findings demonstrate that Polycomb sub-compartments and their antagonism with nuclear lamina association are fundamental organizational features of genome structure. More broadly, by jointly measuring nuclear position and Hi-C contacts, our study demonstrates how dynamic changes in compartmentalization and nuclear lamina association represent distinct but interdependent modes of heterochromatin regulation.
A chromosome-length genome assembly and annotation of blackberry (Rubus argutus, cv. ‘Hillquist’)
Authors: Brůna Tomáš , Aryal Rishi , Dudchenko Olga , Sargent Daniel James , Mead Daniel , Buti Matteo , Cavallini Andrea , Hytönen Timo , Andrés Javier , Pham Melanie , Weisz David , Mascagni Flavia , Usai Gabriele , Natali Lucia , Bassil Nahla , Fernandez Gina E. , Lomsadze Alexandre , Armour Mitchell , Olukolu Bode , Poorten Thomas , Britton Caitlin , Davik Jahn , Ashrafi Hamid , Aiden Erez Lieberman , Borodovsky Mark , Worthington Margaret
Published: May 2022

Background

Blackberries (Rubus spp.) are the fourth most economically important berry crop worldwide. Genome assemblies and annotations have been developed for Rubus species in subgenus Idaeobatus, including black raspberry (R. occidentalis), red raspberry (R. idaeus), and R. chingii, but very few genomic resources exist for blackberries and their relatives in subgenus Rubus.

Findings

Here we present a chromosome-length assembly and annotation of the diploid blackberry germplasm accession ‘Hillquist’ (R. argutus). ‘Hillquist’ is the only known source of primocane-fruiting (annual-fruiting) in tetraploid fresh-market blackberry breeding programs and is represented in the pedigree of many important cultivars worldwide. The ‘Hillquist’ assembly, generated using PacBio long reads scaffolded with Hi-C sequencing, consisted of 298 Mb, of which 270 Mb (90%) was placed on seven chromosome-length scaffolds with an average length of 38.6 Mb. Approximately 52.8% of the genome was composed of repetitive elements. The genome sequence was highly collinear with a novel maternal haplotype-resolved linkage map of the tetraploid blackberry selection A-2551TN and genome assemblies of R. chingii and red raspberry. A total of 38,503 protein-coding genes were predicted using the assembly and Iso-Seq and RNA-seq data, of which 72% were functionally annotated.

Conclusions

The utility of the ‘Hillquist’ genome has been demonstrated here by the development of the first genotyping-by-sequencing based linkage map of tetraploid blackberry and the identification of several possible candidate genes for primocane-fruiting within the previously mapped locus. This chromosome-length assembly will facilitate future studies in Rubus biology, genetics, and genomics and strengthen applied breeding programs.