bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors for Major Amputation for Midfoot Ulcers in Hospitalized Patients With Diabetes
Authors: Moon Kyung-Chul , Son Ji-Won , Han Seung-Kyu , Kim Jae-Yeon
Published: March 2021

PURPOSE:

The purpose of this study was to investigate the risk factors for major amputation in persons hospitalized with diabetic foot ulcers involving the midfoot.

DESIGN:

Retrospective study.

SUBJECTS AND SETTING:

Between January 2003 and May 2019, a total of 1931 patients with diabetes were admitted to the diabetic wound center for the management of foot ulcers. Among the admitted patients, 169 patients with midfoot ulcers were included in this study. One hundred fifty-four patients (91%) healed without major amputation, while 15 patients (9%) healed post–major amputation.

METHODS:

Data related to 88 potential risk factors including demographics, ulcer condition, vascularity, bioburden, neurology, and serology were collected from patients in these 2 groups for comparison. Univariate and multivariate logistic regression analyses were performed to analyze risk factors for major amputation.

RESULTS:

Among the 88 potential risk factors, 15 showed statistically significant differences between the 2 groups. Using univariate analysis of 88 potential risk factors, 8 showed statistically significant differences. Using stepwise multiple logistic regression analysis, 3 of the 8 risk factors remained statistically significant. Multivariate-adjusted odds ratios for deep ulcers invading bone, cardiac disorders, and Charcot foot were 26.718, 18.739, and 16.997, respectively.

CONCLUSION:

The risk factors for major amputation in patients hospitalized with diabetic midfoot ulcers included deep ulcers invading the bone, cardiac disorders, and Charcot foot.
Reducing the Incidence of Medical Device–Related Pressure Injuries From Use of CPAP/BiPAP Masks
Authors: Arundel Linda , Irani Evelyn , Barkema George
Published: March 2021

PURPOSE:

The purpose of this work was to reduce the number of hospital-acquired pressure injuries on the nasal bridge resulting from the use of continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP) therapy.

PARTICIPANTS AND SETTING:

Patients with medical device–related pressure injuries (MDRPI) receiving continuous/intermittent CPAP/BiPAP in a 12-bed critical care unit in a Magnet-designated, 182-bed community hospital in the mid-Atlantic region of the United States.

APPROACH:

An interprofessional team collaborated to assess factors contributing to an increase in MDRPI development in critical care unit patients using CPAP/BiPAP. Patient dependency on the high-pressurized oxygen results in nurse reluctance to remove the mask and consequently, conduct a partial or incomplete skin assessment. The project consisted of conducting a literature search on MDRPI, developing a standard work process for skin assessment and documentation in the medical record, using skin protection under the mask, and evaluating whether a different model of mask would minimize pressure on the nasal bridge.

OUTCOMES:

Through active collaboration, the interprofessional team implemented standard work processes, completed product evaluation of masks, and monitored key process indicators related to documentation of daily and every 4-hour skin assessments, implementation of a thin foam dressing under the CPAP/BiPAP mask for any nonblanchable or blanchable erythema, and escalation to the certified wound, ostomy, and continence nurse. In 2016, the unit identified 4 CPAP/BiPAP mask-related MDRPIs. By December 2017, only 1 stage 1 injury was identified and it resolved quickly after appropriate assessment and prompt interventions. This showed a 75% reduction in actual injuries with a zero escalation to stage 2 or greater injuries.

IMPLICATIONS FOR PRACTICE:

An interprofessional team approach to CPAP/BiPAP-related MDRPI improved patient outcomes in critical care unit patients.
Italian Guidelines for the Nursing Management of Enteral and Urinary Stomas in Adults
Authors: Roveron Gabriele , Barbierato Maria , Rizzo Gianluca , Parini Dario , Bondurri Andrea , Veltri Marco , Pata Francesco , Cattaneo Francesco , Tafuri Alessandro , Forni Cristiana , Ferrara Francesco
Published: March 2021

PURPOSE:

This article is an executive summary of Italian guidelines for nursing management of enteral and urinary ostomies in adults.

METHODS:

Scoping review and generation of evidence and consensus-based clinical guidelines.

SEARCH STRATEGY:

The Multidisciplinary Italian Study group for STOmas (MISSTO) was founded in 2018. This group created guidelines for management of enteral and urinary ostomies in adults based on a scoping review of the literature. The research included previous guidelines, systematic reviews, meta-analyses, randomized clinical trials, cohort studies, and case reports. Five main topics were identified: “stoma preparation,” “stoma creation,” “stoma complications,” “stoma care,” and “stoma reversal” (for enteral stomas).” All the studies were evaluated according to the GRADE system and AGREE II tool. Recommendations were elaborated in the form of statements, with an established grade of recommendation for each statement. For low levels of scientific evidence statements, a consensus conference composed of expert members of the major Italian scientific societies in the field of stoma management and care discussed, corrected, validated, or eliminated the statements. A final version of the guidelines with definitive recommendations was elaborated and prepared for publication.

FINDINGS/CONCLUSIONS:

This document represents the first Italian guidelines on enteral and urinary stoma management to assist nurses caring for persons with an enteral or urinary ostomy.
Sustained Reduction of Nasal Pressure Injuries in the Neonatal Intensive Care Unit With the Use of Bubble Continuous Positive Airway Pressure
Authors: Lawrence Christie , Mohr Lynn D. , Geistkemper Anne , Murphy Sara , Fleming Kellianne
Published: March 2021

PURPOSE:

The purpose of this interprofessional team–driven quality improvement project was to implement a Bubble continuous positive airway pressure (CPAP) Skincare Protocol proactively to prevent potential device-related pressure injuries.

PARTICIPANTS AND SETTING:

The setting was a level 3, 60-bed single patient room neonatal intensive care unit (NICU) located within a Midwest urban academic medical center with more than 200 healthcare providers. Prior to the beginning of this project, the NICU had been using the CPAP apparatus that had documented 6 nasal pressure injuries over a 6-month period. Because of ease of use, the NICU moved to using Bubble CPAP (BCPAP), which is known to place patients at a higher risk of nasal pressure injuries due to the way the apparatus sits inside the nares.

APPROACH:

An evidence-based practice model provided the guiding framework for the development of our BCPAP Skincare Protocol. Knowing that the unit had already documented nasal pressure injuries, the interprofessional-devised protocol was developed to decrease the risk of nasal injuries with the use of BCPAP in premature infants. The protocol was disseminated via an all-healthcare provider educational program.

OUTCOMES:

During the first 3 months postprotocol implementation period, one stage 2 nasal injury was noted and immediately treated and healed without incident. During the next 24-month, postimplementation period, there were zero nasal pressure injuries reported.

IMPLICATIONS FOR PRACTICE:

The healthcare providers found that using an interprofessional team approach in developing and implementing an evidence-based BCPAP Skincare Protocol reduced the incidence of nasal pressure injuries associated with the use of BCPAP in the NICU.
Stepping onto the unknown: reflexes of the foot and ankle while stepping with perturbed perceptions of terrain
Authors: Riddick R. C. , Farris D. J. , Cresswell A. G. , Kuo A. D. , Kelly L. A.
Published: March 2021

Unanticipated variations in terrain can destabilize the body. The foot is the primary interface with the ground and we know that cutaneous reflexes provide important sensory feedback. However, little is known about the contribution of stretch reflexes from the muscles within the foot to upright stability. We used intramuscular electromyography measurements of the foot muscles flexor digitorum brevis (FDB) and abductor hallucis (AH) to show for the first time how their short-latency stretch reflex response (SLR) may play an important role in responding to stepping perturbations. The SLR of FDB and AH was highest for downwards steps and lowest for upwards steps, with the response amplitude for level and compliant steps in between. When the type of terrain was unknown or unexpected to the participant, the SLR of AH and the ankle muscle soleus tended to decrease. We found significant relationships between the contact kinematics and forces of the leg and the SLR, but a person's expectation still had significant effects even after accounting for these relationships. Motor control models of short-latency body stabilization should not only include local muscle dynamics, but also predictions of terrain based on higher level information such as from vision or memory.
Pelistega ratti sp. nov. from Rattus norvegicus of Hainan island
Authors: Zhou Xiaojun , Xuan Duanduan , Hu Shoukui , Du Jiang , Pu Ji , Jin Dong , Zhao Fan , Yin Feifei , Cui Xiuji , Huang Yi , Wang Gaoyu , Wu Qiang , Lu Gang , Niu Lina
Published: March 2021

Two strains (NLN63T and NLN82) of Gram-stain-negative, oxidase- and catalase-positive, bacilli-shaped organisms were isolated from the faecal samples of two separate Rattus norvegicus in Baisha county of Hainan Province, Southern PR China. Phylogenetic analysis based on the near full-length 16S rRNA sequences revealed that strain NLN63T belongs to the genus

Pelistega

, having maximum similarity to

Pelistega suis

CCUG 64465T (97.1 %),

Pelistega europaea

CCUG 39967T (96.2 %) and

Pelistega indica

DSM 27484T (96.2 %), respectively. The phylogenomic tree built on 553 core genes from genomes of 20 species in the genus

Pelistega

and other adjacent genera further confirmed that strains NLN63T and NLN82 form a distinct subline and exhibit specific phylogenetic affinity with

P. europaea

CCUG 39967T. In digital DNA–DNA hybridization analyses, strain NLN63T showed low estimated DNA reassociation values (21.4–22.6 %) with the type strains of the species in the genus

Pelistega

. The DNA G+C contents of strains NLN63T and NLN82 were 37.3 and 37.1 mol%, respectively. Strain NLN63T had a unique MALDI-TOF MS profile, contained Q-8 as the major quinone and C16 : 0, summed feature 8 (C18 : 1
 ω7c/C18 : 1
 ω6c or both) and summed feature 3 (C16 : 1
 ω7c/C16 : 1
 ω6c or both) as the dominant fatty acids. Based upon these polyphasic characterization data obtained from the present study, a novel species of the genus

Pelistega

, Pelistega ratti sp. nov., is proposed with NLN63T (=GDMCC 1.1697T=JCM 33788T) as the type strain.
Immune response to SARS-CoV-2 variants of concern in vaccinated individuals
Authors: Becker Matthias , Dulovic Alex , Junker Daniel , Ruetalo Natalia , Kaiser Philipp D. , Pinilla Yudi T. , Heinzel Constanze , Haering Julia , Traenkle Bjoern , Wagner Teresa R. , Layer Mirjam , Mehrlaender Martin , Mirakaj Valbona , Held Jana , Planatscher Hannes , Schenke-Layland Katja , Krause Gérard , Strengert Monika , Bakchoul Tamam , Althaus Karina , Fendel Rolf , Kreidenweiss Andrea , Koeppen Michael , Rothbauer Ulrich , Schindler Michael , Schneiderhan-Marra Nicole
Published: March 2021

The SARS-CoV-2 pandemic virus is consistently evolving with mutations within the receptor binding domain (RBD)1 being of particular concern2-4. To date, there is little research into protection offered following vaccination or infection against RBD mutants in emerging variants of concern (UK3, South African5, Mink6 and Southern California7). To investigate this, serum and saliva samples were obtained from groups of vaccinated (Pfizer BNT-162b28), infected and uninfected individuals. Antibody responses among groups, including salivary antibody response and antibody binding to RBD mutant strains were examined. The neutralization capacity of the antibody response against a patient-isolated South African variant was tested by viral neutralization tests and further verified by an ACE2 competition assay. We found that humoral responses in vaccinated individuals showed a robust response after the second dose. Interestingly, IgG antibodies were detected in large titers in the saliva of vaccinated subjects. Antibody responses showed considerable differences in binding to RBD mutants in emerging variants of concern. A substantial reduction in RBD binding and neutralization was detected for the South African variant. Taken together our data reinforces the importance of administering the second dose of Pfizer BNT-162b2 to acquire high levels of neutralizing antibodies. High antibody titers in saliva suggest that vaccinated individuals may have reduced transmission potential. Substantially reduced neutralization for the South African variant highlights importance of surveillance strategies to detect new variants and targeting these in future vaccines.
Trends over time in the risk of adverse outcomes among patients with SARS-CoV-2 infection
Authors: Ioannou George N. , O’Hare Ann M. , Berry Kristin , Fan Vincent S , Crothers Kristina , Eastment McKenna C. , Locke Emily , Green Pamela , Shah Javeed A. , Dominitz Jason A.
Published: March 2021

Objectives

We aimed to describe trends in the incidence of adverse outcomes among patients who tested positive for SARS-CoV-2 between February and September 2020 within a national healthcare system.

Setting

US Veterans Affairs national healthcare system.

Participants

Enrollees in the VA healthcare system who tested positive for SARS-CoV-2 between 2/28/2020 and 9/30/2020 (n=55,952).

Outcomes

Death, hospitalization, intensive care unit (ICU) admission and mechanical ventilation within 30 days of testing positive.The incidence of these outcomes was examined among patients infected each month and trends were evaluated using an interrupted time-series analysis.

Results

Between February and July 2020, during the first wave of the US pandemic, there were marked downward trends in the 30-day incidence of hospitalization (44.2% to 15.8%), ICU admission (20.3% to 5.3%), mechanical ventilation (12.7% to 2.2%), and death (12.5% to 4.4%), with subsequent stabilization between July and September 2020. These trends persisted after adjustment for sociodemographic characteristics, comorbid conditions, and documented symptoms and after additional adjustment for laboratory test results among hospitalized patients, including among subgroups admitted to the ICU and treated with mechanical ventilation. Among hospitalized patients, use of hydroxychloroquine (56.5% to 0%), azithromycin (48.3% to 16.6%) vasopressors (20.6% to 8.7%), and dialysis (11.6% to 3.8%) decreased while use of dexamethasone (3.4% to 53.1%), other corticosteroids (4.9% to 29.0%) and remdesivir (1.7% to 45.4%) increased from February to September.

Conclusions

Among patients who tested positive for SARS-CoV-2 in a large national US healthcare system, risk for a range of adverse outcomes decreased markedly between February and July, with subsequent stabilization from July to September. These trends were not explained by changes in measured baseline patient characteristics.
Limited metacognitive access to one’s own facial expressions
Authors: Ciston Anthony B , Forster Carina , Brick Timothy R , Kühn Simone , Verrel Julius , Filevich Elisa
Published: March 2021

As humans we communicate important information through fine nuances in our facial expressions, but because conscious motor representations are noisy, we might not be able to report these fine but meaningful movements. Here we measured how much explicit metacognitive information young adults have about their own facial expressions. Participants imitated pictures of themselves making facial expressions and triggered a camera to take a picture of them while doing so. They then rated confidence (how well they thought they imitated each expression). We defined metacognitive access to facial expressions as the relationship between objective performance (how well the two pictures matched) and subjective confidence ratings. Metacognitive access to facial expressions was very poor when we considered all face features indiscriminately. Instead, machine learning analyses revealed that participants rated confidence based on idiosyncratic subsets of features. We conclude that metacognitive access to own facial expressions is partial, and surprisingly limited.
Post-2020 Kunming 30% target can easily protect all endemic sharks and rays in the Western Indian Ocean and more
Authors: Cheok Jessica , Jabado Rima W. , Ebert David A. , Dulvy Nicholas K.
Published: March 2021

Sharks and rays are possibly the most threatened Class of marine fishes and their declines can be halted if protected areas are optimised to benefit these species. We identify spatial priorities for all 63 endemic sharks and rays in the marine biodiversity hotspot, the Western Indian Ocean (WIO). Collectively, while the WIO nations currently surpass the 10% Aichi ocean protection target, this amounts to a dismal protection of only 1.57% of each species’ distribution range. We show that the entire ranges of all endemics can be achieved by protecting 11% of EEZs of WIO nations, well within reach of the new 30% of oceans by 2030 target. Regional management bodies exist, which if taken advantage of to implement shark and ray management, provide opportunities to implement more efficient management across the region. We recommend key management actions to implement and explicit incentivisation of international cooperation in the post-2020 biodiversity framework.

Science for Society

The past decade has seen massive growth in the establishment of marine protected areas (MPAs), driven by the Aichi biodiversity target of protecting 10% of all ocean areas. This expansion of MPAs, however, has largely occurred in areas residual to extractive uses, often coinciding with less threatened areas of lower conservation value. This coming decade will see a further push to ensure 30% of the oceans are protected by 2030. It is important to understand how existing and future MPAs should be placed to benefit threatened biodiversity. Currently this is unclear for sharks and rays, comprising a species group that is the most evolutionarily distinct vertebrate radiation in the world and also one of the most threatened. We identify both regional and national conservation priorities for expanding marine protected areas to benefit all 63 endemic sharks and rays occurring in the Western Indian Ocean region. We find that the region has already exceeded the 10% ocean protection target, but this amounts to an average of only 1.57% protection of the distribution ranges of these species. We show that protecting the top 10% priority sites will conserve almost half of the geographic range of each species yet require only 1.16% of the total EEZ – a tiny fraction of the 30% by 2030 target. We also show that regional collaboration among all nations can result in more spatially efficient conservation priorities. We recommend that the post-2020 biodiversity framework needs to explicitly incentivise regional cooperation between nations to efficiently achieve urgent targets and maximise benefits to biodiversity.
The effect of task demands on the neural patterns generated by novel instruction encoding
Authors: Sobrado Alberto , Palenciano Ana F. , González-García Carlos , Ruz María
Published: March 2021

Verbal instructions allow fast and optimal implementation of novel behaviors. Previous research has shown that different control-related variables structure neural activity in frontoparietal regions during the encoding of novel instructed tasks. However, it is uncertain whether different task goals modulate the organizing effect of these variables. In this study, we investigated whether the neural encoding of three task-relevant variables (dimension integration, response set complexity and target category) is modulated by implementation and memorization demands. To do so, we combined functional Magnetic Resonance Imaging (fMRI), an instruction-following paradigm and multivariate analyses. We addressed how and where distributed activity patterns encoded the instructions’ variables and the impact of the implementation and memorization demands on the fidelity of these representations. We further explored the nature of the neural code underpinning this process. Our results reveal, first, that the content of to-be-implemented and to-be-memorized instructions is represented in overlapping brain regions, flexibly using a common neural code across tasks. Importantly, they also suggest that preparing to implement the instructions increases the decodability of task-relevant information in frontoparietal areas, in comparison with memorization demands. Overall, our work emphasizes both similarities and differences in task coding under the two contextual demands. These findings qualify the previous understanding of novel instruction processing, suggesting that representing task attributes in a generalizable code, together with the increase in encoding fidelity induced by the implementation goals, could be key mechanisms for proactive control in novel scenarios.
Spike-frequency dependent coregulation of multiple ionic conductances in fast-spiking cells forces a metabolic tradeoff
Authors: Ban Yue , Maltby Rosalie , Markham Michael R.
Published: March 2021

High-frequency action potentials (APs) allow rapid information acquisition and processing in neural systems, but create biophysical and metabolic challenges for excitable cells. The electric fishEigenmannia virescensimages its world and communicates with high-frequency (200-600 Hz) electric organ discharges (EODs) produced by synchronized APs generated at the same frequency in the electric organ cells (electrocytes). We cloned three previously unidentified Na+-activated K+channel isoforms from electroctyes (eSlack1, eSlack2, and eSlick1). In electrocytes, mRNA transcript levels of the rapidly-activating eSlick, but not the slower eSlack1 or eSlack2, correlated with EOD frequency across individuals. In addition, transcript levels of an inward-rectifier K+channel, a voltage-gated Na+channel, and Na+,K+-ATPases also correlated with EOD frequency while a second Na+channel isoform did not. Computational simulations showed that maintaining electrocyte AP waveform integrity as firing rates increase requires scaling conductances in accordance with these mRNA expression correlations, causing AP metabolic costs to increase exponentially.
Diversification, Spread, and Admixture of Octoploid Strawberry in the Western Hemisphere
Authors: Bird Kevin A. , Hardigan Michael A. , Ragsdale Aaron P. , Knapp Steven J. , VanBuren Robert , Edger Patrick P.
Published: March 2021

Premise of the study

Octoploid strawberry (Fragaria sp.) has a complex evolutionary history that has until recently been intractable due to limitations of available genomic resources. While recent work has further uncovered the evolutionary history of the octoploid strawberry, there are still open questions. Much is still unknown about the evolutionary relationship of the wild octoploid species,Fragaria virginianaandFragaria chiloensis, and gene flow within and among species after the original formation of the octoploid genome.

Methods

We leveraged a diversity collection of wild octoploid eco-types of strawberry representing the recognized subspecies and ranging from Alaska to Southern Chile, and a high density SNP array to investigate wild octoploid strawberry evolution. Evolutionary relationships are interrogated with phylogenetic analysis and genetic clustering algorithms. Additionally, admixture among and within species is assessed with model-based and tree-based approaches.

Key Results

Phylogenetic analysis revealed that the two octoploid strawberry species are monophyletic sister lineages. The genetic clustering results show substructure between North Americana and South AmericanF. chiloensispopulations. Additionally, model-based and tree-based methods support gene flow within and among the two octoploid species, including newly identified admixture in the HawaiianF. chiloensissubsp.sandwicensispopulation that appears to be from an ancestralF. chiloensispopulation.

Conclusion

F. virginianaandF. chiloensisare supported as monophyletic and sister lineages. All but one of the subspecies recognized within both octoploid species show extensive paraphyly. Furthermore, the phylogenetic relationship amongF. chiloensispopulations supports a single population range expansion southward from North America. The inter- and intraspecific relationships of octoploid strawberry are complex and suggest substantial and deep gene flow between sympatric populations among and within species.
Antimalarial mass drug administration in large populations and the evolution of drug resistance
Authors: Nguyen Tran Dang , Tran Thu Nguyen-Anh , Parker Daniel M. , White Nicholas J , Boni Maciej F
Published: March 2021

Mass drug administration (MDA) with antimalarials has been shown to reduce prevalence and interrupt transmission in small populations, in populations with reliable access to antimalarial drugs, and in populations where sustained improvements in diagnosis and treatment are possible. Effective MDA eliminates drug-resistant parasites which has the long-term benefit of extending the useful therapeutic life of first-line therapies for all populations, not just the focal population where MDA was carried out. However, in order to plan elimination measures effectively, it is necessary to characterize the conditions under which failed MDA could exacerbate resistance. We use an individual-based stochastic model ofPlasmodium falciparumtransmission to evaluate this risk in large populations (>40K) where access to antimalarial treatments may not be uniformly high and where re-importation of drug-resistant parasites may be common. We find that drug-resistance evolution can be accelerated by MDA when all three of the following conditions are met: (1) strong genetic bottlenecking that falls short of elimination, (2) re-importation of resistant genotypes, and (3) continued selection pressure during routine case management post-MDA. Accelerated resistance levels are not immediate but follow the rebound of malaria cases post-MDA, if this is allowed to occur. Crucially, resistance is driven by the selection pressure during routine case management post-MDA and not the selection pressure exerted during the MDA itself. Second, we find that increasing treatment coverage post-MDA increases the probability of local elimination in low-transmission regions (PfPR < 2%) in scenarios with both low and high levels of drug-resistance importation. This emphasizes the importance of preparation and planning to ensure that MDA has a high probability of leading to elimination, and the necessity of supporting public health infrastructure to provide high coverage of diagnosis and treatment post-MDA.
How Stimulus Statistics Affect The Receptive Fields of V1 Cells
Authors: Almasi Ali , Sun Shi Hai , Yunzab Molis , Jung Young Jun , Meffin Hamish , Ibbotson Michael R.
Published: March 2021

We studied the changes that neuronal RF models undergo when the statistics of the stimulus are changed from those of white Gaussian noise (WGN) to those of natural scenes (NS). Fitting the model to data estimates both a cascade of linear filters on the stimulus, as wells as the static nonlinearities that map the output of the filters to the neuronal spike rates. We found that cells respond differently to these two classes of stimuli, with mostly higher spike rates and shorter response latencies to NS than to WGN. The most striking finding was that NS resulted in RFs that had additional uncovered filters than did WGN. This finding was not an artefact of the higher spike rates but rather related to a change in coding. Our results reveal a greater extent of nonlinear processing in V1 neurons when stimulated using NS compared to WGN. Our findings indicate the existence of nonlinear mechanisms that endow V1 neurons with context-dependent transmission of visual information.
Trajectory inference across multiple conditions with condiments: differential topology, progression, differentiation, and expression
Authors: de Bézieux Hector Roux , Van den Berge Koen , Street Kelly , Dudoit Sandrine
Published: March 2021

In single-cell RNA-sequencing (scRNA-seq), gene expression is assessed individually for each cell, allowing the investigation of developmental processes, such as embryogenesis and cellular differentiation and regeneration, at unprecedented resolutions. In such dynamic biological systems, grouping cells into discrete groups is not reflective of the biology. Cellular states rather form a continuum, e.g., for the differentiation of stem cells into mature cell types. This process is often represented via a trajectory in a reduced-dimensional representation of the scRNA-seq dataset.

While many methods have been suggested for trajectory inference, it is often unclear how to handle multiple biological groups or conditions, e.g., inferring and comparing the differentiation trajectories of wild-type and knock-out stem cell populations.

In this manuscript, we present a method for the estimation and downstream interpretation of cell trajectories across multiple conditions. Our framework allows the interpretation of differences between conditions at the trajectory, cell population, and gene expression levels. We start by integrating datasets from multiple conditions into a single trajectory. By comparing the conditions along the trajectory’s path, we can detect large-scale changes, indicative of differential progression. We also demonstrate how to detect subtler changes by finding genes that exhibit different behaviors between these conditions along a differentiation path.
rdacca.hp: an R package for generalizing hierarchical and variation partitioning in multiple regression and canonical analysis
Authors: Lai Jiangshan , Zou Yi , Zhang Jinlong , Peres-Neto Pedro
Published: March 2021

Canonical analysis, a generalization of multiple regression to multiple response variables, is widely used in ecology. Because these models often involve large amounts of parameters (one slope per response per predictor), they pose challenges to model interpretation. Currently, multi-response canonical analysis is constrained by two major challenges. Firstly, we lack quantitative frameworks for estimating the overall importance of single predictors. Secondly, although the commonly used variation partitioning framework to estimate the importance of groups of multiple predictors can be used to estimate the importance of single predictors, it is currently computationally constrained to a maximum of four predictor matrices.

We established that commonality analysis and hierarchical partitioning, widely used for both estimating predictor importance and improving the interpretation of single-response regression models, are related and complementary frameworks that can be expanded for the analysis of multiple-response models.

In this application, we aim at: a) demonstrating the mathematical links between commonality analysis, variation and hierarchical partitioning; b) generalizing these frameworks to allow the analysis of any number of responses, predictor variables or groups of predictor variables in the case of variation partitioning; and c) introducing and demonstrating the usage of the R packagerdacca.hpthat implements these generalized frameworks.
Generation of human blastocyst-like structures from pluripotent stem cells
Authors: Fan Yong , Min Zhe-Ying , Alsolami Samhan , Ma Zheng-Lai , Zhong Ke , Pei Wen-Di , Zhang Pu-Yao , Kang Xiang-Jin , Zhang Ying-Ying , Zhu Hai-Ying , Qiao Jie , Li Mo , Yu Yang
Published: March 2021

Human blastocysts are comprised of the first three cell lineages of the embryo: trophectoderm, epiblast, and primitive endoderm, all of which are essential for early development and organ formation1,2. However, due to ethical concerns and restricted access to human blastocysts, we lack a comprehensive understanding of early human embryogenesis. To bridge this knowledge gap, we need a reliable model system that recapitulates early stages of human embryogenesis. Here we report a ∼three-dimensional (3D), two-step induction protocol for generating blastocyst-like structures (EPS-blastoids) from human extended pluripotent stem (EPS) cells. Morphological and single-cell transcriptomic analyses revealed that EPS-blastoids contain key cell lineages and are transcriptionally similar to human blastocysts. Furthermore, EPS-blastoids also exhibited the developmental potential to undergo post-implantation morphogenesis in vitro to form structures with a cellular composition and transcriptome signature similar to human embryos that had been cultured in vitro for 8 or 10 days. In conclusion, human EPS-blastoids provide a new experimental platform for studying early developmental stages of the human embryo.

Highlights

A method for generating human blastoids from EPS cells.

Human blastoids resemble blastocysts in terms of morphology and cell lineage composition.

Single-cell transcriptomic analyses reveal EPI, PE, and TE cell lineages in human blastoids.

Human blastoids mimic in vitro the morphogenetic events of pre- and early post-implantation stages.
End-to-end Learning of Evolutionary Models to Find Coding Regions in Genome Alignments
Authors: Mertsch Darvin , Stanke Mario
Published: March 2021

1

Motivation

The comparison of genomes using models of molecular evolution is a powerful approach for finding or towards understanding functional elements. In particular, comparative genomics is a fundamental building brick in building high-quality, complete and consistent annotations of ever larger sets of alignable genomes.

Results

We here present our new program ClaMSA that classifies multiple sequence alignments using a phylogenetic model. It uses a novel continuous-time Markov chain machine learning layer, named CTMC, that is learned end-to-end together with (recurrent) neural networks for a learning task. We trained ClaMSA discriminately to classify aligned codon sequences that are candidates of coding regions into coding or non-coding and obtained six times fewer false positives for this task on vertebrate and fly alignments than existing methods at the same true positive rate. ClaMSA and the CTMC layer are general tools that could be used for other machine learning tasks on tree-related sequence data.

Availability

Freely fromhttps://github.com/Gaius-Augustus/clamsa.
Direct sulphate-TOR signalling controls transcriptional reprogramming for shoot apex activation inArabidopsis
Authors: Yu Yongdong , Zhong Zhaochen , Ma Liuyin , Xiang Chengbin , Xu Ping , Xiong Yan
Published: March 2021

Photosynthetic plants play a primary role for the global sulphur cycle in the earth ecosystems by reduction of inorganic sulphate from the soil to organic sulphur-containing compounds. How plants sense and transduce the sulphate availability in soil to mediate their growth remains largely unclear. The target of rapamycin (TOR) kinase is an evolutionarily conserved master regulator of nutrient sensing and metabolic signalling to control cell proliferation and growth in all eukaryotes. Here, we discovered that inorganic sulphate exhibits higher potency than organic cysteine and glutathione for activation of TOR and cell proliferation in the leaf primordium to promote true leaf development inArabidopsis. Chemical genetic analyses further revealed that this sulphate activation of TOR is independent of the sulphate-assimilation process and glucose-energy signalling. Significantly, tissue specific transcriptome analyses uncovered previously unknown sulphate-orchestrating genes involved in DNA replication, cell proliferation, autophagy and various secondary metabolism pathways, which are completely depending on TOR signalling. Systematic comparison between the sulphate- and glucose-TOR controlled transcriptome further revealed that, as the central growth integrator, TOR kinase can sense different upstream nutrient signals to control both shared and unique transcriptome networks, therefore, precisely modulate plant proliferation, growth and stress responses.
The first multi-tissue diel genome-scale metabolic model of a woody plant highlights suberin biosynthesis pathways inQuercus suber
Authors: Cunha Emanuel , Silva Miguel , Chaves Ines , Demirci Huseyin , Lagoa Davide Rafael , Lima Diogo , Rocha Miguel , Rocha Isabel , Dias Oscar
Published: March 2021

In the last decade, genome-scale metabolic models have been increasingly used to study plant metabolic behavior at the tissue and multi-tissue level under different environmental conditions.Quercus suber, also known as the cork oak tree, is one of the most important forest communities of the Mediterranean/Iberian region. In this work, we present the genome-scale metabolic model of theQ. suber(iEC7871), the first of a woody plant. The metabolic model comprises 7871 genes, 6231 reactions, and 6481 metabolites across eight compartments. Transcriptomics data was integrated into the model to obtain tissue-specific models for the leaf, inner bark, and phellogen, with specific biomass compositions. The tissue-specific models were merged into a diel multi-tissue metabolic model to predict interactions among the three tissues at the light and dark phases. The metabolic models were also used to analyze the pathways associated with the synthesis of suberin monomers. Nevertheless, the models developed in this work can provide insights into other aspects of the metabolism ofQ. suber, such as its secondary metabolism and cork formation.
Towards a broad-spectrum antiviral, the myristoyltransferase inhibitor IMP-1088 suppresses viral replication – the Yellow fever NS5 is myristoylated
Authors: Immerheiser Melissa , Zimniak Melissa , Hilpert Helen , Geiger Nina , König Eva-Maria , Bodem Jochen
Published: March 2021

Although a potent Yellow fever vaccine is available since 1937, up to 200.000 severe cases are reported per year, which indicates that virus vaccines require additional support by antiviral therapies. Direct-acting antiviral drugs against severe and widespread diseases, such as DENV and Yellow fever infections with more than millions of diagnosed diseases per year, are still not available. Since antivirals’ development against neglected diseases is uneconomical, a broadspectrum antiviral compound would be of public benefit. Here, we show that IMP-1088, a recently published myristoyltransferase-1/2 inhibitor suppressing Rhino- and Polioviruses, inhibits replication of HIV-1, Yellow fever virus, Dengue virus, Vaccinia virus, CMV, and human Herpesvirus 8 in the low nanomolar range, indicating that IMP-1088 has broad-range activity against different pathogenic virus families. The inhibition relies on virally encoded myristoylation signals since Zika, Chikungunya, and Enterovirus 71 are not affected by IMP-1088. Furthermore, we show that the Yellow fever NS5 protein is myristoylated and IMP-1088 treatment of Dengue and Yellow fever infected cells leads to a re-localisation of the viral NS5 proteins.

Author Summary

Treatment of viral diseases requires the development of tailored drugs specific to inhibit certain virus families. This specificity results in missing treatment options for important human pathogens such as Yellow fever and Dengue virus infection since the development is laborious and costly. Substances acting on various virus families could solve this problem. Here, we describe that IMP-1088, an inhibitor of the cellular myristoyltransferase, inhibits HIV-1, Dengue virus, Yellow fever viruses, Vaccinia virus, and Herpesviruses at low concentrations, which do not affect cell proliferation. Viruses without predicated myristoylation sites, such as Zika viruses, were not inhibited by IMP-1088. Since no experimental evidence was provided that Yellow fever virus proteins are myristoylated, we analysed the post-translational modification of Yellow fever NS5 protein. We determined the subcellular localisation to understand the mechanism of the IMP-1088 mediated suppression and could show that both the Dengue and the Yellow fever NS5 proteins are re-localised by IMP-1088 treatment.
Comparison of hybrid learning and remote education in the implementation of the “Adopt a Microorganism” methodology
Authors: Armellini Bárbara Rodrigues Cintra , Luna Alexandre La , Bueris Vanessa , de Almeida Alisson Pinto , Tamais Alicia Moraes , Júnior Flávio Krzyzanowski , Reiter Victor Samuel Hasten , Lellis-Santos Camilo , de Cássia Café Ferreira Rita
Published: March 2021

The Internet has changed the way teachers and students access information and build knowledge. The recent COVID-19 pandemic has created challenges for both teachers and students and a demand for new methodologies of remote learning. In the life sciences, mixing online content with practical activities represents an even greater challenge. In microbiology, the implementation of an active teaching methodology, the #Adopt project, based on the social network Facebook®, represents an excellent option for connecting remote education with classroom activities. In 2020, the version applied in high school, “Adopt a Microorganism”, was adapted to meet the demands of emergency remote education owing to the suppression of face-to-face activities caused by the pandemic. In the present study, we assessed how the change in methodology impacted the discourse richness of students from high school integrated with technical education in the Business Administration program of the Federal Institute of São Paulo, Sorocaba Campus. Three questionnaires related to the groups of microorganisms (Archaea, Bacteria, Virus, Fungi, and Protozoan) were applied. The students’ responses in the 2019 and 2020 classes were compared concerning content richness and multiplicity of concepts through the application of the Shannon diversity index, an approach that is generally used to assess biodiversity in different environments. The observed results suggest that remote learning provided students with a conceptual basis and richness of content equivalent to that achieved by students subjected to the hybrid teaching model. In conclusion, this study suggests that the #Adopt project methodology increases students’ discourse richness in microbiology even without face-to-face traditional classes.
Mapping of Quantitative Trait Locus (QTLs) that contribute to Drought Tolerance in a Recombinant Inbred Line Population of horsegram (Macrotyloma uniflorum)
Authors: Katoch Megha , Chahota R.K.
Published: March 2021

Horsegram (Macrotyloma uniflorum) is a drought hardy legume which can be grown in varied soil and temperature regime. It is an important food legume with environmental, nutritive and medicinal benefits. But in terms of genetic improvement it still lags behind other legumes. To get insight into the genetics of tolerance to drought stress, quantitative trait loci for drought tolerance traits were identified using an intraspecific mapping population comprising of 162 F8Recombinant Inbred Lines derived from a cross between HPKM249 and HPK4. A total of 2011 markers were screened on parental lines for polymorphism survey, out of which 493 markers were found to be polymorphic and used for genotyping of the RIL population. Of these 493 polymorphic markers, 295 were assigned to ten linkage groups at LOD 3.5 spanning 1541.7cM with a mean distance of 5.20 cM between adjacent markers. This linkage map along with the phenotypic data for drought tolerance traits was used to identify regions of the horsegram genome in which the genes for the qualitative traits linked to drought tolerance located. A total of seven QTLs were identified for six different drought related traits. One QTL for malondialdehyde content on linkage group 2, two QTLs for root length on linkage group 3 & 9, one QTL each for proline content and chlorophyll content under drought stress on linkage group 4, one QTL each for root dry weight and root fresh weight on linkage group 5 were identified using composite interval mapping. The linkage map and identified QTLs will be utilized in Marker Assisted Breeding and increase our understanding on the physiology of drought stress tolerance. It will also aid in molecular breeding efforts for further genetic improvement of horsegram.
Multiple nucleotide polymorphism DNA markers for the accurate evaluation of genetic variations
Authors: Fang Zhiwei , Li Lun , Zhou Junfei , You Aiqing , Gao Lifen , Li Tiantian , Chen Hong , Han Ruixi , Cui Yehan , Chen Lihong , Xiao Huafeng , Zhang Jing , Xu Na , Fu Xiqin , Zhang Jianan , Li Xiuting , Ma Aijin , Zhang Weixiong , Peng Hai
Published: March 2021

DNA markers are an essential tool for the detection and evaluation of genetic variations, a central theme in genetics and biology. Effective markers must be highly reproducible, polymorphic, accurate and efficient to profile. We developedmultiple dispersed nucleotide polymorphism(MNP) DNA marker and an efficient MNP genotyping method calledMNP-Seq. The MNP marker was 17.48% more polymorphic than the highly polymorphic marker of microsatellites on a collection of hybrid rice plants. When applied to genotype more than 80,000 individual MNP markers of diploid rice and polyploidy hybrid cotton varieties which were notoriously difficult to genotype accurately, MNP-Seq finished in two days and achieved accuracies of 99.999% and 99.988%, respectively. We adopted MNP-Seq to reveal the ubiquitous, albeit subtle and neglected, genetic heterogeneities in homonyms of Nipponbare rice, a popular model organism for plant biology. This result raised a question on the consistency of the published results using the model plant. We also used MNP-Seq to accurately and efficiently determine the identities of plant varieties, a key but difficult problem for the protection of plant intellectual property rights. While being applied to plants in the current study, the MNP marker and MNP-Seq are general and readily applicable to similar problems in animals and micro-organisms.
Integrative genomics reveals paths to sex dimorphism inSalix purpureaL.
Authors: Hyden Brennan , Carlson Craig H. , Gouker Fred E. , Schmutz Jeremy , Barry Kerrie , Lipzen Anna , Sharma Aditi , Sandor Laura , Tuskan Gerald A. , Feng Guanqiao , Olson Matthew S. , DiFazio Stephen P. , Smart Lawrence B.
Published: March 2021

Sex dimorphism and gene expression were studied in developing catkins in 159 F2individuals from the bioenergy cropSalix purpurea, and potential mechanisms and pathways for regulating sex development were explored. Differential expression, eQTL, bisulfite sequencing, and network analysis were used to characterize sex dimorphism, detect candidate master regulator genes, and identify pathways through which the sex determination region (SDR) may mediate sex dimorphism. Eleven genes are presented as candidates for master regulators of sex, supported by gene expression and network analyses. These include genes putatively involved in hormone signaling, epigenetic modification, and regulation of transcription. eQTL analysis revealed a suite of transcription factors and genes involved in secondary metabolism and floral development that were predicted to be under direct control of the sex determination region. Furthermore, data from bisulfite sequencing and small RNA sequencing revealed strong differences in expression between males and females that would implicate both of these processes in sex dimorphism pathways. These data indicate that the mechanism of sex determination inSalix purpureais likely different from that observed in the related genusPopulus. This further demonstrates the dynamic nature of SDRs in plants, which involves a multitude of mechanisms of sex determination and a high rate of turnover.