bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of indoor biological air quality at a mass gathering event in an unimproved exhibition facility during the COVID-19 pandemic using a novel air sampling technology
Authors: Gordon Julian , Abdullah Osama , Reboulet Rachel , Hanson Kara , Sadowski Christine , Rennels Hunter , Kuemmerle Steve , Tuttle Richard , Solocinski Kristen , Knight Brittany , Wilkinson Jacob , Macgregor-Skinner Gavin
Published: March 2022

The objective was to evaluate the determination of biomarkers of air quality during a mass gathering event at a convention center using a novel air sampling device, AirAnswers®. This sampler has previously only been used in smaller locations. Here it was run at five crowded locations within the exhibit area for the four days duration of a trade show. The AirAnswers® device uses electro-kinetic flow to sample air at high rates and capture bio-aerosols on grounded electrodes in assayable form. Cartridges were removed from the devices and immediately conveyed to the Inspirotec facility in North Chicago, where assays were performed.

Biomarkers determined were for allergens and molds previously described for this system. Testing for a new marker, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was also included. The method was validated by determination of capture efficiency with reference to an impinger sampler in a Class III controlled environment chamber. Average capture efficiency for triplicate runs was 14%. One SARS-CoV-2 positive sample as found at the registration area, which was physically separate from the main exhibit area.

Cat allergen Fel d 1was found in four of the locations, dog allergen Can f 1 at two. The airborne biomarker of mold proliferation, (1→3)-β-D-Glucan, was above the assay range in all locations. The widespread presence of this mold marker could be accounted for by signs of water leakage. A generic 18S RNA marker for mold was developed and similarly showed the presence of mold in all locations, as was a genus marker for penicillium. A species marker for Cladosporium cladosporioides was in two locations. Species markers for Eurotium amstelodami and Trichoderma viride were each in a single location.

The main findings were of the widespread presence of mold markers, and the sporadic appearance of SARS-CoV-2. Masking was recommended but not enforced.
Use of Convalescent Plasma Therapy with Best Available Treatment (BAT) among Hospitalized COVID-19 Patients: A Multi-Center Study
Authors: Mesina Flordeluna , Julian Jomell , Relos Jesus , Torres Rosalio , Comia Maureen Via M. , Ongkingco June Marie P. , Lafavilla Jimmy R.
Published: March 2022

The COVID-19 disease caused by SARS-CoV2 virus has gripped the whole world with overwhelming strain in our health system. Currently, there are no standard guidelines in its treatment but the possible benefits of convalescent plasma in limiting complications and severity of the COVID-19 disease have emerged.

OBJECTIVE

This study aims to determine the effectiveness and safety of using convalescent plasma in improving the clinical course of hospitalized patients diagnosed with COVID-19 disease admitted at University of Santo Tomas and Makati Medical Center.

METHODS

This study is a quasi-experimental (prospective analytical), and multi-center study involving 65 patients diagnosed with COVID-19 Disease who received convalescent plasma, with 65 patients who only received best available treatment serving as age-gender-matched control.

RESULTS

Median age of the population who received convalescent plasma was 60 years old, mostly male (68%), and manifested severe pneumonia (47%). There was noted statistically signifcant decrease between the pre-and post-treatment values of hemoglobin (p=0.04) and LDH (p=0.086). There was also statistically significant increase in platelet counts (p=0.01). WBC and PaO2 increased while ferritin and PFR decreased after convalescent plasma transfusion, however, these were not statistically significant. Length of stay and clinical outcome of those who received convalescent plasma were then compared to age-gender matched controls who only received best available treatment. There was noted statistically significant difference between length of stay (p=0.00) among those who received convalescent plasma as compared to those who did not. This was seen across severe and critically ill COVID-19 patients. There was also more mortality seen in the best available treatment alone group, but this was non-significant.

CONCLUSIONS

Convalescent plasma use showed no significant impact in the recovery rate and outcome of patients who received it as compared to those who did not, however, its use was proven to be safe among all patients regardless of the level of severity and clinical profile.
Dictionary learning for integrative, multimodal, and scalable single-cell analysis
Authors: Hao Yuhan , Stuart Tim , Kowalski Madeline , Choudhary Saket , Hoffman Paul , Hartman Austin , Srivastava Avi , Molla Gesmira , Madad Shaista , Fernandez-Granda Carlos , Satija Rahul
Published: February 2022

Mapping single-cell sequencing profiles to comprehensive reference datasets represents a powerful alternative to unsupervised analysis. Reference datasets, however, are predominantly constructed from single-cell RNA-seq data, and cannot be used to annotate datasets that do not measure gene expression. Here we introduce ‘bridge integration’, a method to harmonize singlecell datasets across modalities by leveraging a multi-omic dataset as a molecular bridge. Each cell in the multi-omic dataset comprises an element in a ‘dictionary’, which can be used to reconstruct unimodal datasets and transform them into a shared space. We demonstrate that our procedure can accurately harmonize transcriptomic data with independent single cell measurements of chromatin accessibility, histone modifications, DNA methylation, and protein levels. Moreover, we demonstrate how dictionary learning can be combined with sketching techniques to substantially improve computational scalability, and harmonize 8.6 million human immune cell profiles from sequencing and mass cytometry experiments. Our approach aims to broaden the utility of single-cell reference datasets and facilitate comparisons across diverse molecular modalities.

Availability

Installation instructions, documentations, and vignettes are available at http://www.satijalab.org/seurat
Resident T cells orchestrate adipose tissue remodeling in a site peripheral to infection
Authors: Kabat Agnieszka M. , Hackl Alexandra , Sanin David E. , Zeis Patrice , Grzes Katarzyna M. , Baixauli Francesc , Kyle Ryan , Caputa George , Edwards-Hicks Joy , Villa Matteo , Rana Nisha , Curtis Jonathan D. , Castoldi Angela , Cupovic Jovana , Dreesen Leentje , Sibilia Maria , Pospisilik J. Andrew , Urban Joseph F. , Grün Dominic , Pearce Erika L. , Pearce Edward J.
Published: February 2022

Infection with helminth parasites can affect adiposity, but underlying mechanisms that regulate this process are unclear. We found that fat content of mesenteric adipose tissue (mAT) declined in mice during infection with gut-restricted parasitic worms. This was associated with the accumulation of metabolically activated, immunostimulatory cytokine- and extracellular matrix-secreting multipotent stromal cells, which had potential to differentiate into preadipocytes. Concomitantly, mAT became infiltrated with Th2 lymphocytes that took up long-term residence and responded to signals from stromal cells by producing stromal cell-stimulating cytokines, including Amphiregulin. Signals delivered by Amphiregulin to stromal cells were required for immunity to infection. Our findings reveal intricate intercellular communication between Th2 cells and adipocyte progenitors and link immunity to intestinal infection to T cell-dependent effects on the adipocyte lineage.
Discovery of a novel coronavirus in Swedish bank voles (Myodes glareolus)
Authors: Wasberg Anishia , Raghwani Jayna , Li Jinlin , Pettersson John H.-O. , Lindahl Johanna F. , Lundkvist Åke , Ling Jiaxin
Published: February 2022

We identified a novel Betacoronavirus from bank voles (Myodes glareolus) in Grimsö, Sweden. Repeated detection over three years and an overall prevalence of 3.4% suggests the virus commonly occurs in bank voles. Furthermore, phylogenetic analyses indicate the virus belongs to a highly divergent Embecovirus lineage predominantly associated with bank voles.
Mouse models of COVID-19 recapitulate inflammatory pathways rather than gene expression
Authors: Bishop Cameron R. , Dumenil Troy , Rawle Daniel J. , Le Thuy T. , Yan Kexin , Tang Bing , Hartel Gunter , Suhrbier Andreas
Published: February 2022

BACKGROUND

How well mouse models recapitulate the transcriptional profiles seen in humans remains debatable, with both conservation and diversity identified in various settings. The K18-hACE2 mouse model has been widely used for evaluation of new interventions for COVID-19.

METHOD

Herein we use RNA-Seq data and bioinformatics approaches to compare the transcriptional responses in the SARS-CoV-2 infected lungs of K18-hACE2 mice with those seen in humans.

RESULTS

Overlap in differentially expressed genes was generally poor (≈20-30%), even when multiple studies were combined. The overlap was not substantially improved when a second mouse model was examined wherein hACE was expressed from the mouse ACE2 promoter. In contrast, analyses of immune signatures and inflammatory pathways illustrated highly significant concordances between the species.

CONCLUSION

As immunity and immunopathology are the focus of most studies, these hACE2 transgenic mouse models can thus be viewed as representative and relevant models of COVID-19.
ProbeTools: Designing hybridization probes for targeted genomic sequencing of diverse and hypervariable viral taxa
Authors: Kuchinski Kevin S. , Duan Jun , Himsworth Chelsea , Hsiao William , Prystajecky Natalie A.
Published: February 2022

Background

Sequencing viruses in many specimens is hindered by excessive background material from hosts, microbiota, and environmental organisms. Consequently, enrichment of target genomic material is necessary for practical high-throughput viral genome sequencing. Hybridization probes are widely used for enrichment in many fields, but their application to viral sequencing faces a major obstacle: it is difficult to design panels of probe oligo sequences that broadly target many viral taxa due to their rapid evolution, extensive diversity, and genetic hypervariability. To address this challenge, we created ProbeTools, a package of bioinformatic tools for generating effective viral capture panels, and for assessing coverage of target sequences by probe panel designs in silico. In this study, we validated ProbeTools by designing a panel of 3,600 probes for subtyping the hypervariable haemagglutinin (HA) and neuraminidase (NA) genome segments of avian-origin influenza A viruses (AIVs). Using in silico assessment of AIV reference sequences and in vitro capture on egg-cultured viral isolates, we demonstrated effective performance by our custom AIV panel and ProbeTools’ suitability for challenging viral probe design applications.

Results

Based on ProbeTool’s in silico analysis, our panel provided broadly inclusive coverage of 14,772 HA and 11,967 NA reference sequences. 90% of these HA and NA references sequences had 90.8% and 95.1% of their nucleotide positions covered in silico by the panel respectively. We also observed effective in vitro capture on a representative collection of 23 egg-cultured AIVs that included isolates from wild birds, poultry, and humans and representatives from all HA and NA subtypes. 42 of 46 HA and NA segments had over 98.3% of their nucleotide positions significantly enriched by our custom panel. These in vitro results were further used to validate ProbeTools’ in silico coverage assessment algorithm; 89.2% of in silico predictions were concordant with in vitro results.

Conclusions

ProbeTools generated an effective panel for subtyping AIVs that can be deployed for genomic surveillance, outbreak prevention, and pandemic preparedness. Effective probe design against hypervariable AIV targets also validated ProbeTools’ design and coverage assessment algorithms, demonstrating their suitability for other challenging viral capture applications.
Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution
Authors: Starr Tyler N. , Greaney Allison J. , Hannon William W. , Loes Andrea N. , Hauser Kevin , Dillen Josh R. , Ferri Elena , Farrell Ariana Ghez , Dadonaite Bernadeta , McCallum Matthew , Matreyek Kenneth A. , Corti Davide , Veesler David , Snell Gyorgy , Bloom Jesse D.
Published: February 2022

SARS-CoV-2 has evolved variants with substitutions in the spike receptor-binding domain (RBD) that impact its affinity for ACE2 receptor and recognition by antibodies. These substitutions could also shape future evolution by modulating the effects of mutations at other sites—a phenomenon called epistasis. To investigate this possibility, we performed deep mutational scans to measure the effects on ACE2 binding of all single amino-acid mutations in the Wuhan-Hu-1, Alpha, Beta, Delta, and Eta variant RBDs. Some substitutions, most prominently N501Y, cause epistatic shifts in the effects of mutations at other sites, thereby shaping subsequent evolutionary change. These epistatic shifts occur despite high conservation of the overall RBD structure. Our data shed light on RBD sequence-function relationships and facilitate interpretation of ongoing SARS-CoV-2 evolution.
Impact of body mass index on 5-year survival rates in patients undergoing allogeneic hematopoietic stem cell transplantation
Authors: Aoyama Takashi , Notsu Akifumi , Ichimaru Koki , Tsuji Masanori , Yoshitsugu Kanako , Fukaya Masafumi , Enami Terukazu , Ikeda Takashi
Published: February 2022

Background

The association between cancer survival and body mass index (BMI) has been elucidated. However, the impact of patients’ baseline characteristics on allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes remains unclear.

Objectives

To examine the baseline clinical factors associated with 5-year survival rates in patients undergoing allo-HSCT.

Study design

This was a retrospective exploratory observational study. Patients (n=113, average age: 55 years; 52 women) who underwent allo-HSCT at the Division of Hematology and Stem Cell Transplantation, Shizuoka Cancer Center, between January 2008 and March 2015 were included in this study.

Results

The 5-year survival rate (65%) was associated with the baseline geriatric nutritional risk index (GNRI; odds ratio [OR]=1.20, 95% confidence interval [CI]: 1.03–1.36, P <0.01) and the BMI (OR=1.06, 95% CI: 1.02–1.12, P <0.01). The cut-off values for BMI and GNRI were 20.5 kg/m2 and 101 points, respectively (area under the curve, 0.65017 and 0.67637, respectively). The 5-year survival rate was poorer for patients with sarcopenia (41.5%) than for those without sarcopenia prior to allo-HSCT (p=0.05).

Conclusions

BMI and GNRI values before allo-HCST pre-treatment were independent predictors of the 5-year survival rates. Patients undergoing allo-HSCT may require nutritional interventions during pre-treatment to reduce the risk of sarcopenia, which affects their survival rates.
Self-management of depression and anxiety amongst frail older adults in the United Kingdom: a qualitative study
Authors: Nair Pushpa , Walters Kate R. , Aw Su , Gould Rebecca L. , Kharicha Kalpa , Buszewicz Marta , Frost Rachael
Published: February 2022

Objectives

Depression and anxiety are common in frail older people and are associated with high levels of morbidity and mortality, yet they typically face greater barriers to accessing mental health treatments than younger people and express preferences for self-managing their symptoms. This study aims to explore frail older adults’ experiences of self-managing symptoms of depression and/or anxiety.

Design

Qualitative semi-structured interviews, exploring experiences of depression and/or anxiety, ways participants self-managed these and the contexts within which this took place. Interviews were audio-recorded and transcribed verbatim.

Participants

28 frail older adults in the United Kingdom, purposively sampled for neighbourhood, frailty and symptoms of anxiety/depression.

Analysis

Thematic analysis to inductively derive themes from the data.

Results

Our findings suggest that frail older adults find maintaining routines, engaging in meaningful and creative activities and socialising important to self-manage depression and anxiety. These could all be adapted to the level of frailty experienced. Stoicism, acceptance, faith or addressing the perceived cause were helpful in some situations and for some personalities. Distraction and avoidance were helpful for more severe symptoms or where the causes of symptoms could not be resolved. Self-management strategies were less well-established for anxiety symptoms, especially when linked to newer health fears and worries about the future.

Conclusions

Developing services and sources of information that support and facilitate key therapeutic components of self-management, which align with older adults’ preferred coping styles and take into account levels of frailty, may be a way of supporting frail older people waiting for mental health treatments or those who prefer not to access these. Greater awareness of anxiety and how it can be self-managed in frail older people is needed.
A Novel Home-Based Study of Circadian Rhythms: Design, Rationale, and Methods for the Circadia Study
Authors: Vlasac Irma , Bormes Gregory , Do Elizabeth , Benkhoukha Selma , Diallo Naby , Fryou Noah L. , Gioia Siena , Joseph Clarence , Kuan Anne , Lapan Jennifer , Oluwadara David ,   the Pepper Team, Saxena Richa , Scheer Frank , Woodson Faraji , Lane Jacqueline
Published: February 2022

The Circadia Study (Circadia) is a novel “direct to participant” research study investigating the genetics of circadian rhythm disorders. The long-term goals of this study are to better understand the genetics of circadian rhythm disorders, investigate the efficacy and accessibility of an at-home, self-directed DLMO collection, to improve health outcomes in the future for patients with circadian rhythm disorders, and to address the specific needs of the circadian rhythm disorder patient population.

In this manuscript, we briefly outline the standard methods of both circadian biology research protocols and circadian rhythm disorder diagnostic procedures. We describe some of the inherent limitations of current circadian research and diagnostic methods, which motivated our development of and informed the design of the Circadia Study. We discuss the main goals of the Circadia Study, and we outline key features of our study design that build upon current study methods and address limitations. Finally, we describe specific aspects of the Circadia Study, including our study population, data collection methods, and standard operating procedures so that others may replicate aspects of the study design.

The Circadia Study is approved for human subject research by the Mass General Brigham Institutional Review Board, Protocol # 2020P002779.
Breakthrough SARS-CoV-2 Infection Outcomes in Vaccinated Patients with Chronic Liver Disease and Cirrhosis: A National COVID Cohort Collaborative Study
Authors: Ge Jin , Digitale Jean C. , Pletcher Mark J. , Lai Jennifer C. ,   the N3C Consortium
Published: February 2022

Background and Aims

The incidence and outcomes of breakthrough SARS-CoV-2 infections in vaccinated chronic liver disease (CLD) patients have not been well-characterized in non-veteran populations. We used the National COVID Cohort Collaborative (N3C), a dataset of 10.7 million patients, of whom 0.9 million have vaccination data, to describe outcomes in vaccinated CLD patients.

Methods

We identified all CLD patients with or without cirrhosis regardless of vaccination status who had SARS-CoV-2 testing in the N3C Data Enclave as of 1/15/2022. We used Poisson regression to estimate incidence rates of breakthrough infections and Cox survival analyses to associate vaccination status with all-cause mortality at 30 days among infected CLD patients.

Results

We isolated 278,457 total CLD patients: 43,079 (15%) vaccinated and 235,378 (85%) unvaccinated. Of the 43,079 vaccinated CLD patients, 32,838 (76%) were without cirrhosis and 10,441 (24%) were with cirrhosis. Estimated incidence rates for breakthrough infections were 5.6 and 5.1 per 1,000 person-months for 27,235 fully vaccinated CLD patients without cirrhosis and for 8,218 fully vaccinated CLD patients with cirrhosis, respectively.

Of the 68,048 unvaccinated and 10,441 vaccinated CLD patients with cirrhosis in our cohort, 15% and 3.7%, respectively, developed SARS-CoV-2 infection. The combined 30-day all-cause rate of mechanical ventilation (without death) or death after SARS-CoV-2 infection for unvaccinated and vaccinated CLD patients with cirrhosis were 15.2% and 7.7%, respectively. Compared to unvaccinated patients with cirrhosis, full vaccination was associated with a 0.34-times adjusted hazard of death at 30 days.

Conclusions

In this N3C Data Enclave study, breakthrough infection rates were similar amongst CLD patients with and without cirrhosis. Full vaccination was associated with a 66% reduction in risk of all-cause mortality among CLD patients with cirrhosis after infection. These results provide an additional impetus for increasing vaccination uptake among patients with severe liver disease.
Multimodal MRI examination of structural and functional brain changes in older women with breast cancer in the first year of antiestrogen hormonal therapy
Authors: McDonald Brenna C. , Van Dyk Kathleen M. , Deardorff Rachael L. , Bailey Jessica N. , Zhai Wanting , Carroll Judith E. , Root James C. , Ahles Tim A. , Mandelblatt Jeanne S. , Saykin Andrew J.
Published: March 2022

Purpose

Cancer patients are concerned about treatment-related cognitive problems. We examined effects of antiestrogen hormonal therapy on brain imaging metrics in older women with breast cancer.

Methods

Women aged 60+ treated with hormonal therapy only and matched non-cancer controls (n=29/group) completed MRI and objective and self-reported cognitive assessment at pre-treatment/enrollment and 12 months later. Gray matter was examined using voxel-based morphometry (VBM), FreeSurfer, and brain age calculations. Functional MRI (fMRI) assessed working memory-related activation. Analyses examined cross-sectional and longitudinal differences and tested associations between brain metrics, cognition, and days on hormonal therapy.

Results

The cancer group showed regional reductions over 12 months in frontal, temporal, and parietal gray matter on VBM, reduced FreeSurfer cortical thickness in prefrontal, parietal, and insular regions, and increased working memory-related fMRI activation in frontal, cingulate, and visual association cortex. Controls showed only reductions in fusiform gyrus on VBM and FreeSurfer temporal and parietal cortex thickness. Women with breast cancer showed higher estimated brain age and lower regional gray matter volume than controls at both timepoints. The cancer group showed a trend toward decreased performance in attention, processing speed, and executive function over time. There were no significant associations between brain imaging metrics and cognition or days on hormonal therapy.

Conclusion

Older women with breast cancer showed brain changes in the first year of hormonal therapy. Increased brain activation during working memory processing may be a sign of functional compensation for treatment-related structural changes. This hypothesis should be tested in larger samples over longer time periods.
Semantic speech networks linked to formal thought disorder in early psychosis
Authors: Nettekoven Caroline R , Diederen Kelly , Giles Oscar , Duncan Helen , Stenson Iain , Olah Julianna , Gibbs-Dean Toni , Collier Nigel , Vértes Petra E , Spencer Tom J , Morgan Sarah E , McGuire Philip
Published: March 2022

Background and Hypothesis

Mapping a patient’s speech as a network has proved to be a useful way of understanding formal thought disorder in psychosis. However, to date, graph theory tools have not incorporated the semantic content of speech, which is altered in psychosis.

Study Design

We developed an algorithm, “netts”, to map the semantic content of speech as a network, then applied netts to construct semantic speech networks for a general population sample, and a clinical sample comprising patients with first episode psychosis (FEP), people at clinical high risk of psychosis (CHR-P), and healthy controls.

Study Results

Semantic speech networks from the general population were more connected than size-matched randomised networks, with fewer and larger connected components, reflecting the non-random nature of speech. Networks from FEP patients were smaller than from healthy participants, for a picture description task but not a story recall task. For the former task, FEP networks were also more fragmented than those from controls; showing more, smaller connected components. CHR-P networks showed fragmentation values in-between FEP patients and controls. A clustering analysis suggested that semantic speech networks captured novel signal not already described by existing NLP measures. Network features were also related to negative symptom scores and scores on the Thought and Language Index, although these relationships did not survive correcting for multiple comparisons.

Conclusions

Overall, these data suggest that semantic networks can enable deeper phenotyping of formal thought disorder in psychosis. We are releasing Netts as an open Python package alongside this manuscript.
LipidMS 3.0: an R-package and a web-based tool for LC-MS/MS data processing and lipid annotation
Authors: Alcoriza-Balaguer María Isabel , García-Cañaveras Juan Carlos , Ripoll-Esteve Francisco Javier , Roca Marta , Lahoz Agustín
Published: March 2022

LipidMS was initially envisioned to use fragmentation rules and data-independent acquisition (DIA) for lipid annotation. However, data-dependent acquisition (DDA) remains the most widespread acquisition mode for untargeted LC-MS/MS-based lipidomics. Here we present LipidMS 3.0, an R package that not only adds DDA and new lipid classes to its pipeline, but also the required functionalities to cover the whole data analysis workflow from pre-processing (i.e., peak-peaking, alignment and grouping) to lipid annotation. We applied the new workflow in the data analysis of a commercial human serum pool spiked with 68 lipid standards acquired in the full scan, DDA and DIA modes. When focusing on the detected lipid standard features and total identified lipids, LipidMS 3.0 data pre-processing performance is similar to XCMS, whereas it complements the annotations provided by MS-DIAL, one of the most widely used tools in lipidomics. To extend and facilitate LipidMS 3.0 usage among less experienced R-programming users, the workflow was also implemented as a web-based application.

Availability and Implementation

The LipidMS R-package is freely available at https://CRAN.R-project.org/package=LipidMS and as a website at http://www.lipidms.com.

Contact

juancarlos_garcia@iislafe.es, agustin.lahoz@uv.es
Human mesenchymal stem cells and derived extracellular vesicles reduce sensory neuron hyperexcitability and pain-related behaviors in a mouse model of osteoarthritis
Authors: Ai Minji , Hotham William E. , Pattison Luke A. , Ma Qingxi , Henson Frances M.D. , Smith Ewan St. John.
Published: February 2022

Osteoarthritis (OA) is a common degenerative joint disease characterized by joint pain and stiffness. In humans, mesenchymal stem cells (MSCs) and derived extracellular vesicles (MSC-EVs) have been reported to alleviate pain in knee OA. Here, we used the destabilization of the medial meniscus (DMM) mouse model of OA to investigate mechanisms by which MSCs and MSC-EVs influence pain-related behavior. We found that MSC and MSC-EV treated DMM mice displayed improved OA pain-related behavior (i.e. locomotion, digging and sleep) compared to untreated DMM mice. Improved behavior was not the result of reduced joint damage, but rather knee-innervating sensory neurons from MSC and MSC-EV treated mice did not display the hyperexcitability observed in untreated DMM mice. Furthermore, we found that MSC-EVs normalize sensory neuron hyperexcitability induced by nerve growth factorin vitro. Our study suggests that MSCs and MSC-EVs may reduce pain in OA by direct action on peripheral sensory neurons.

Teaser

Mesenchymal stem cells and secreted extracellular vesicles normalize sensory neuron excitability to reduce pain.
The GENOMES UNCOUPLED1 protein has an ancient, highly conserved role in chloroplast gene expression but not in retrograde signalling
Authors: Honkanen Suvi , Small Ian
Published: February 2022

The pentatricopeptide repeat protein GENOMES UNCOUPLED1 (GUN1) is required for chloroplast-to-nucleus signalling in response to plastid stress during chloroplast development in Arabidopsis thaliana but its exact molecular function remains unknown.

We analysed GUN1 sequences in land plants and streptophyte algae. We tested functional conservation by complementation of the Arabidopsis gun1 mutant with GUN1 genes from the streptophyte alga Coleochate orbicularis or the liverwort Marchantia polymorpha. We also analysed the transcriptomes of M. polymorpha gun1 knock-out mutant lines during chloroplast development.

GUN1 evolved within the streptophyte algal ancestors of land plants and is highly conserved among land plants but missing from the Rafflesiaceae that lack chloroplast genomes. GUN1 genes from C. orbicularis and M. polymorpha restore chloroplast retrograde signalling and suppress the cold-sensitive phenotype of the Arabidopsis gun1 mutant. However, GUN1 is not required for chloroplast retrograde signalling in the liverwort M. polymorpha.

Our findings suggest that GUN1 is an ancient protein that evolved within the streptophyte algal ancestors of land plants before the first plants colonised land more than 470 million years ago. Its primary role is likely to be in chloroplast gene expression and its role in chloroplast retrograde signalling probably evolved more recently.
Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies
Authors: De Bastiani Marco Antônio , Bellaver Bruna , Brum Wagner S. , Souza Debora G. , Ferreira Pamela C. L. , Rocha Andreia S. , Povala Guilherme , Ferrari-Souza João Pedro , Benedet Andrea L. , Ashton Nicholas J. , Karikari Thomas K. , Zetterberg Henrik , Blennow Kaj , Rosa-Neto Pedro , Pascoal Tharick A. , Zimmer Eduardo R. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2022

Introduction

In Alzheimer’s disease clinical research, glial fibrillary acidic protein (GFAP) released into the cerebrospinal fluid and blood is widely measured and perceived as a biomarker of reactive astrogliosis. However, it was demonstrated that GFAP levels differ in individuals presenting with amyloid-β (Aβ) or tau pathology. The molecular underpinnings behind this specificity are unexplored. Here we investigated biomarker and transcriptomic associations of GFAP-positive astrocytes with Aβ and tau pathologies in humans and mouse models.

Methods

We studied 90 individuals with plasma GFAP, Aβ- and Tau-PET to investigate the association between biomarkers. Then, transcriptomic analysis in hippocampal GFAP-positive astrocytes isolated from mouse models presenting Aβ (PS2APP) or tau (P301S) pathologies was applied to explore differentially expressed genes (DEGs), Gene Ontology processes, and protein-protein interaction networks associated with each phenotype.

Results

In humans, we found that plasma GFAP associates with Aβ but not tau pathology. Unveiling the unique nature of GFAP-positive astrocytic responses to Aβ or tau pathology, mouse transcriptomics showed scarce overlap of DEGs between the Aβ and tau mouse models, While Aβ GFAP-positive astrocytes were overrepresented with genes associated with proteostasis and exocytosis-related processes, tau hippocampal GFAP-positive astrocytes presented greater abnormalities in functions related to DNA/RNA processing and cytoskeleton dynamics.

Conclusion

Our results offer insights into Aβ- and tau-driven specific signatures in GFAP-positive astrocytes. Characterizing how different underlying pathologies distinctly influence astrocyte responses is critical for the biological interpretation of astrocyte-related biomarker and suggests the need to develop context-specific astrocyte targets to study AD.

Funding

This study was supported by Instituto Serrapilheira, Alzheimer’s Association, CAPES, CNPq and FAPERGS.
TGF-β1 induced S100 family protein expression is associated with epithelial to mesenchymal transition states and poor survival in pancreatic cancer
Authors: Jie Low Ronnie Ren , Fung Ka Yee , Gao Hugh , Preaudet Adele , Dagley Laura F. , Yousef Jumana , Lee Belinda , Larsen Rune H. , Kershaw Nadia J. , Burgess Antony W. , Gibbs Peter , Hollande Frédéric , Griffin Michael D.W. , Grimmond Sean M. , Putoczki Tracy L.
Published: February 2022

Epithelial-mesenchymal transition (EMT) is a continuum that includes epithelial, partial EMT (P-EMT) and mesenchymal states, each of which are associated with cancer progression, invasive capabilities and ultimately metastasis. We have employed a lineage traced sporadic model of pancreatic cancer to generate a murine organoid biobank from primary and secondary tumors, including sublines that have undergone P-EMT and complete EMT (C-EMT). Using an unbiased proteomics approach, we found that the morphology of the organoids predicts the EMT state, with solid organoids associated with a P-EMT signature. We also observed that exogenous TGFβ1 induces a solid organoid morphology that is associated with changes in the S100 family, C-EMT and the formation of high-grade tumors. S100A4 may represent a useful biomarker to predict EMT state, disease progression and outcome for pancreatic cancer patients.
Infection by a eukaryotic gut parasite in wild Daphnia sp. associates with a distinct bacterial community
Authors: Rajarajan Amruta , Wolinska Justyna , Walser Jean-Claude , Mäder Minea , Spaak Piet
Published: February 2022

Host-associated bacterial communities can play an important role in host fitness and resistance to diseases. Yet, few studies have investigated tripartite interaction between a host, parasite and host-associated bacterial communities in natural settings. Here, we use 16S amplicon sequencing to compare gut- and body-bacterial communities of wild water fleas belonging to the Daphnia longispina complex, between uninfected hosts and those infected with the common and virulent eukaryotic gut parasite Caullerya mesnili (Family: Ichthyosporea). We report community-level changes in host-associated bacteria with the presence of the parasite infection; namely decreased alpha diversity and increased beta diversity at the site of infection, i.e. host gut (but not host body). We also report decreased abundance of bacterial taxa proposed elsewhere to be beneficial for the host, and an appearance of taxa specifically associated with infected hosts. Our study highlights the host-microbiota-infection link in a natural system and raises questions about the role of host-associated microbiota in natural disease epidemics as well as the functional roles of bacteria specifically associated with infected hosts.
Proteomic analysis of human milk reveals nutritional and immune benefits in the colostrum from mothers with COVID-19
Authors: Guo Juanjuan , Tan Minjie , Zhu Jing , Tian Ye , Liu Huanyu , Luo Fan , Wang Jianbin , Huang Yanyi , Zhang Yuanzhen , Yang Yuexin , Wang Guanbo
Published: February 2022

The range of benefits breastfeeding provides neonates and infants include nutrition, improved neonatal survival, and reduced morbidity from certain diseases. It also aids maternal health by speeding postpartum recovery. However, due to concern about the risk of SARS-CoV-2 transmission and the lack of evidence of breastmilk’s protective effects against the virus, whether mothers with COVID-19 should be encouraged to breastfeed is under debate. Here, we present the results of proteomic and glycoproteomic studies of breast milk (colostrum and mature milk) from mothers with confirmed COVID-19. All colostrum samples exhibited significantly upregulated immune-related proteins, especially whey proteins with antiviral properties against SARS-CoV-2, and increased glycosylation levels and heterogeneity at those proteins. Such adaptive differences in milk from COVID-19 mothers tend to fade in mature milk from the same mothers one month postpartum. These results suggest the immune benefits of colostrum from mothers with COVID-19 and provide molecular-level insights that aid breastmilk feeding decisions in cases of active infection.
Data based slurry treatment decision tree to minimise antibiotic resistance and pathogen transfer while maximising nutrient recycling
Authors: Do Thi Thuy , Nolan Stephen , Hayes Nicky , O’Flaherty Vincent , Burgess Catherine , Brennan Fiona , Walsh Fiona
Published: March 2022

Direct application of pig slurry to agricultural land, as a means of nutrient recycling, introduces pathogens, antibiotic resistant bacteria, or genes, to the environment. With global environmental sustainability policies mandating a reduction in synthetic fertilisation and a commitment to a circular economy it is imperative to find effective on-farm treatments of slurry that maximises its fertilisation value and minimises risk to health and the environment. We assessed and compared the effect of storage, composting, and anaerobic digestion on pig slurry microbiome, resistome and nutrient content. Shotgun metagenomic sequencing and HT-qPCR arrays were implemented to understand the dynamics across the treatments. Our results identified that each of the treatment methods had advantages and disadvantages, depending on the parameter measured. The data suggests that storage and composting are optimal for the removal of human pathogens and anaerobic digestion for the reduction in AMR genes and mobile genetic elements. The nitrogen content is increased in storage and AD and reduced in composting. Thus, depending on the requirement for increased or reduced nitrogen the optimum treatment varies. Combining the results indicates that composting provides the greatest gain by reducing risk to human health and the environment. Network analysis revealed reducing Proteobacteria and Bacteroidetes while increasing Firmicutes will reduce the AMR content. KEGG analysis identified no significant change in the pathways across all treatments. This novel study provides a data driven decision tree to determine the optimal treatment for best practice to minimise pathogen, AMR and excess or increasing nutrient transfer from slurry to environment.

Graphical abstract
Transcriptomic analysis of sorted lung cells revealed a proviral activity of the NF-κB pathway towards SARS-CoV-2
Authors: Bhargava Anvita , Szachnowski Ugo , Chazal Maxime , Foretek Dominika , Aicher Sophie-Marie , Pipoli da Fonseca Juliana , Jeannin Patricia , Beauclair Guillaume , Monot Marc , Morillon Antonin , Jouvenet Nolwenn
Published: February 2022

Investigations of cellular responses to viral infection are commonly performed on mixed populations of infected and uninfected cells or using single-cell RNA sequencing, leading to inaccurate and low-resolution gene expression interpretations. Here, we performed deep polyA+transcriptome analyses and novel RNA profiling of SARS-CoV-2 infected lung epithelial cells, sorted based on the expression of the viral spike (S) protein. Infection caused a massive reduction in mRNAs and lncRNAs, including transcripts coding for antiviral factors, such as interferons (IFN). This absence of IFN signaling probably explained the poor transcriptomic response of bystander cells co-cultured with S+ones. NF-κB pathway and the inflammatory response escaped the global shutoff in S+cells. Functional investigations revealed the proviral function of the NF-κB pathway and the antiviral activity of CYLD, a negative regulator of the pathway. Thus, our transcriptomic analysis on sorted cells revealed additional genes that modulate SARS-CoV-2 replication in lung cells.
A loss-of-function cysteine mutant in fibulin-3 (EFEMP1) forms aberrant extracellular disulfide-linked homodimers and alters extracellular matrix composition
Authors: Woodard DaNae R. , Daniel Steffi , Nakahara Emi , Abbas Ali , DiCesare Sophia M. , Hulleman John D.
Published: February 2022

Fibulin-3 (F3 or EFEMP1) is a disulfide-rich, secreted glycoprotein necessary for maintaining extracellular matrix (ECM) and connective tissue integrity. Two studies have identified distinct autosomal recessive F3 mutations in individuals with Marfan Syndrome-like phenotypes. Herein we characterized how one of these mutations, c.163T>C; p.Cys55Arg (C55R), disrupts F3 secretion, quaternary structure, and function by forming unique extracellular disulfide-linked homodimers. Dual cysteine mutants suggest that the C55R-induced disulfide species forms because of new availability of Cys70 on adjacent F3 monomers. Surprisingly, mutation of single cysteines located near C55 (i.e., C29, C42, C48, C61, C70, C159, and C171) also produced similar extracellular disulfide-linked dimers, suggesting that this is not a phenomenon isolated to the C55R mutant. To assess C55R functionality, F3 knockout (KO) retinal pigmented epithelial (RPE) were generated, followed by reintroduction of wild-type (WT) or C55R F3. F3 KO cells produced lower levels of the ECM remodeling enzyme, matrix metalloproteinase 2 and reduced formation of collagen VI ECM filaments, both of which were partially rescued by WT F3 overexpression. However, C55R F3 was unable to compensate for these same ECM-related defects. Our results highlight the unique behavior of particular cysteine mutations in F3 and uncover potential routes to restore C55R F3 loss-of-function.
Hand Gesture Prediction via Transient-phase sEMG using Transfer Learning of Dilated Efficient CapsNet: Towards Generalization for Neurorobotics
Authors: Tyacke Eion , Reddy Shreyas P. J. , Feng Natalie , Edlabadkar Rama , Zhou Shucong , Patel Jay , Hu Qin , Atashzar S. Farokh
Published: March 2022

There has been an accelerated surge to utilize the deep neural network for decoding central and peripheral activations of the human’s nervous system to boost up the spatiotemporal resolution of neural interfaces used in neurorobotics. Such algorithmic solutions are motivated for use in human-centered robotic systems, such as neurorehabilitation, prosthetics, and exoskeletons. These methods are proved to achieve higher accuracy on individual data when compared with the conventional machine learning methods but are also challenged by their assumption of having access to massive training samples.

Objective

In this letter, we propose Dilated Efficient CapsNet to improve the predictive performance when the available individual data is very minimum and not enough to train an individualized network for controlling a personalized robotic system.

Method

We proposed the concept of transfer learning using a new design of the dilated efficient capsular neural network to relax the need of having access to massive individual data and utilize the field knowledge which can be learned from a group of participants. In addition, instead of using complete sEMG signals, we only use the transient phase, reducing the volume of training samples to 20% of the original and maximizing the agility.

Results

In experiments, we validate our model performance with various amounts of injected personalized training data (25%-100% of transient phase) that is segmented once by time and once by repetition. The results of this paper support the use of transfer learning using a dilated capsular neural network and show that with the use of such a model, the knowledge domain learned on a small number of subjects can be utilized to minimize the need for new data of new subjects while focusing only on the transient phase of contraction (which is a challenging neural interfacing problem).
PSMA-bearing extracellular vesicles secreted from prostate cancer convert the microenvironment to a tumor-supporting, pro-angiogenic state
Authors: Machado Camila Maria Longo , Skubal Magdalena , Haedicke Katja , Silva Fabio Pittella , Stater Evan Paul , de Oliveira Silva Thais Larissa Araujo , Costa Erico Tosoni , Masotti Cibele , Otake Andreia Hanada , Andrade Luciana Nogueira Sousa , de Souza Junqueira Mara , Hsu Hsiao-Ting , Das Sudeep , Larney Benedict Mc , Pratt Edwin Charles , Romin Yevgeniy , Fan Ning , Manova-Todorova Katia , Pomper Martin , Grimm Jan
Published: February 2022

Extracellular vesicles (EV) are comprised of vesicles budding from cell membranes and smaller intracellular vesicles shed by cells. EV play a role in remodeling the tumor microenvironment (TME) and support tumor progression. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein with a carboxypeptidase function, frequently associated with poor clinical prognosis in prostate cancer (PCa). We previously identified an oncogenic PSMA signaling function in prostate cancer. Others demonstrated that EV isolated from the plasma of patients with high-grade PCa carry PSMA, but so far no pathophysiological effect has been associated with PSMA-bearing EV. Here we demonstrate that EV from PCa cells are able to transfer PSMA and its functionality to cells in the TME. The consequence of that EV-mediated PSMA transfer is an acute to long-term increased secretion of vascular endothelial growth factor-A (VEGF-A), angiogenin, pro-angiogenic and pro-lymphangiogenic mediators and increased 4E binding protein 1 (4EBP-1) phosphorylation in tumors. We compare EV from PCa cells with or without PSMA expression to address the role of PSMA-bearing EV in promoting pro-tumoral changes in the TME using classical molecular biology and novel molecular imaging approaches.
Estimating the overall fraction of phenotypic variance attributed to high-dimensional predictors measured with error
Authors: Mandal Soutrik , Kim Do Hyun , Hua Xing , Li Shilan , Shi Jianxin
Published: March 2022

In prospective genomic studies (e.g., DNA methylation, metagenomics, and transcriptomics), it is crucial to estimate the overall fraction of phenotypic variance (OFPV) attributed to the high-dimensional genomic variables, a concept similar to heritability analyses in genome-wide association studies (GWAS). Unlike genetic variants in GWAS, these genomic variables are typically measured with error due to technical limitation and temporal instability. While the existing methods developed for GWAS can be used, ignoring measurement error may severely underestimate OFPV and mislead the design of future studies. Assuming that measurement error variances are distributed similarly between causal and noncausal variables, we show that the asymptotic attenuation factor equals to the average intraclass correlation coefficients of all genomic variables, which can be estimated based on a pilot study with repeated measurements. We illustrate the method by estimating the contribution of microbiome taxa to body mass index and multiple allergy traits in the American Gut Project. Finally, we show that measurement error does not cause meaningful bias when estimating the correlation of effect sizes for two traits.