bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amino acid availability acts as a metabolic rheostat to determine the magnitude of ILC2 responses
Authors: Hodge Suzanne H. , Krauss Maria Z. , Kaymak Irem , King James , Howden Andrew J.M. , Panic Gordana , Grencis Richard K. , Swann Jonathan R. , Sinclair Linda V. , Hepworth Matthew R. 
Published: June 2022

AbstractGroup 2 innate lymphoid cells (ILC2) are functionally poised, tissue-resident lymphocytes that respond rapidly to damage and infection at mucosal barrier sites. ILC2 reside within complex microenvironments where they are subject to cues from the diet, commensal microbiota and invading pathogens – most notably helminths. Emerging evidence suggests ILC2 are acutely sensitive not only to canonical activating signals, but also perturbations in nutrient and metabolite availability. In the context of helminth infection, we identify amino acid availability as a nutritional cue in regulating ILC2 responses. ILC2 were found to be uniquely pre-primed to import amino acids via the large neutral amino acid transportersSlc7a5andSlc7a8. Cell-intrinsic deletion of these transporters impaired ILC2 expansion, but not cytokine production, in part via tuning of mTOR activation. These findings implicate the import of amino acids as a metabolic requisite for optimal ILC2 responses, and further highlight nutritional cues as critical regulators of innate immune responses within mucosal barrier tissues.
Topology-based fluorescence image analysis for automated cell identification and segmentation
Authors: Panconi L. , Makarova M. , Lambert E. R. , May R.C. , Owen D.M. 
Published: June 2022

AbstractCell segmentation refers to the body of techniques used to identify cells in images and extract biologically relevant information from them; however, manual segmentation is laborious and subjective. We present Topological Boundary Line Estimation using Recurrence Of Neighbouring Emissions (TOBLERONE), a topological image analysis tool which identifies persistent homological image features as opposed to the geometric analysis commonly employed. We demonstrate that topological data analysis can provide accurate segmentation of arbitrarily-shaped cells, offering a means for automatic and objective data extraction. One cellular feature of particular interest in biology is the plasma membrane, which has been shown to present varying degrees of lipid packing, or membrane order, depending on the function and morphology of the cell type. With the use of environmentally-sensitive dyes, images derived from confocal microscopy can be used to quantify the degree of membrane order. We demonstrate that TOBLERONE is capable of automating this task.
A scalable sparse neural network framework for rare cell type annotation of single-cell transcriptome data
Authors: Cheng Yuqi , Fan Xingyu , Zhang Jianing , Li Yu 
Published: June 2022

AbstractCell type annotation is critical to understand the cell population heterogeneity in the single-cell RNA sequencing (scRNA-seq) analysis. Due to their fast, precise, and user-friendly advantages, automatic annotation methods are gradually replacing traditional unsupervised clustering approaches in cell type identification practice. However, current supervised annotation tools are easily overfitting, thus favoring large cell populations but failing to learn the information of smaller populations. This drawback will significantly mislead biological analysis, especially when the rare cell types are important. Here, we present scBalance, an integrated sparse neural network framework that leverages the adaptive weight sampling and dropout techniques for the auto-annotation task. Using 20 scRNA-seq datasets with different scales and different imbalance degrees, we systematically validate the strong performance of scBalance for both intra-dataset and inter-dataset annotation tasks. Furthermore, we also demonstrate the scalability of scBalance on identifying rare cell types in million-level datasets by uncovering the immune landscape in bronchoalveolar cells. Up to now, scBalance is the first and only auto-annotation tool that expands scalability to 1.5 million cells dataset. In addition, scBalance also shows a fast and stable speed outperforming commonly used tools across all scales of datasets. We implemented scBalance in a user-friendly manner that can easily interact with Scanpy, which makes scBalance a superior tool in the increasingly important Python-based platform.
COP9 signalosome component CSN-5 stabilizes PUF proteins FBF-1 and FBF-2 inCaenorhabditis elegansgermline stem cells
Authors: Osterli Emily , Ellenbecker Mary , Wang Xiaobo , Terzo Mikaya , Jacobson Ketch , Cuello DeAnna , Voronina Ekaterina 
Published: June 2022

AbstractRNA-binding proteins FBF-1 and FBF-2 (FBFs) are required for germline stem cell maintenance and the sperm/oocyte switch inCaenorhabditis elegans, though the mechanisms controlling FBF protein levels remain unknown. We identified an interaction between both FBFs and CSN-5, a component of the COP9 (constitutive photomorphogenesis 9) signalosome. Here, we find that the MPN (Mpr1/Pad1 N terminal) metalloprotease domain of CSN-5 interacts with the PUF (Pumilio and FBF) RNA-binding domain of FBFs and the interaction is conserved for human homologs PUM1 and CSN5. The interaction between FBF-2 and CSN-5 can be detectedin vivoby proximity ligation.csn-5mutation results in destabilization of FBF proteins, a decrease in the numbers of germline stem cells, and disruption of the switch from spermatogenesis to oogenesis. The loss ofcsn-5does not decrease the levels of a related PUF protein PUF-3 andcsn-5(lf) phenotype is not enhanced byfbf-1/2depletion, suggesting that the effect is specific to FBFs. The effect ofcsn-5on germline sex determination is largely independent of the COP9 signalosome and is cell autonomous. Surprisingly, regulation of FBF protein levels involves a combination of COP9-dependent and –independent mechanisms differentially affecting FBF-1 and FBF-2. This work supports a previously unappreciated role for CSN-5 in stabilization of germline stem cell regulatory proteins FBF-1 and FBF-2.Author SummaryGerm cell development and reproductive success in the nematodeC. elegansrely on the function of germline stem cells. Continued maintenance of these cells is supported by the activity of conserved RNA-binding proteins FBF-1 and FBF-2 (FBFs). However, it is unknown how FBF protein levels are regulated. Here, we identify a direct interaction between FBFs and CSN-5, a component of the COP9 signalosome best known for its role in regulating protein degradation. We find that CSN-5 promotes FBF stability and allows for accumulation of steady-state protein levels, thereby promoting FBF function. Incsn-5mutants, we find a significant reduction of FBF proteins, decrease of stem cells, and failure to promote oogenesis consistent with compromised FBF function. Furthermore, CSN-5 contributes to FBF protein stability through two mechanisms. This work demonstrates a previously unappreciated role for CSN-5 in stabilization of FBF proteins. Based on our finding that the FBF/CSN-5 interaction is conserved and detectable between homologous human proteins, we speculate this relationship might be relevant for understanding stem cell maintenance in a range of species, from nematodes to humans.
Thermal Pain and Detection Threshold Modulation in Augmented Reality
Authors: Eckhoff Daniel , Sandor Christian , Cheing Gladys L. Y. , Schnupp Jan , Cassinelli Alvaro 
Published: June 2022

ABSTRACTAugmented Reality (AR) overlays computer-generated visual, auditory or other sensory information on the real world. Due to recent advancements in AR it can be difficult for the user to differentiate between sensory information coming from real and virtual objects, leading to interesting phenomena. For example, an AR experience in which users can experience their own hands in flames has been shown to elicit heat illusions on the affected hands. In this study, we investigate the potential that AR has for top-down modulation of pain and thermal perception. We assessed thermal pain and detection thresholds on the participant’s right hand when they experienced that hand covered in virtual flames in AR. We compared that experience to a baseline condition with no additional stimuli as well to a control condition that sees the hand covered by unrealistic blue flames to compensate the distraction factor. We found that experiencing a burning hand in AR induced analgesic and hyperalgesic effects as participants began to feel heat related pain on lower temperatures and cold related pain on higher temperatures. That experience also significantly changed the lowest temperature at which participants started perceiving warmth. These results demonstrate that pain and thermal perception can be manipulated by altering the perception of our body in AR.
Sequencing from leftover material of stored rapid Ag Tests (Ag-RDTs): a gamechanger in genomic surveillance?
Authors: Rector Annabel , Bloemen Mandy , Schiettekatte Gilberte , Maes Piet , Van Ranst Marc , Wollants Elke 
Published: June 2022

ABSTRACTArchived lateral flow antigen-detection rapid diagnostic tests (Ag-RDTs), used in the diagnosis of COVID-19, were successfully used to extract viral nucleic acids for subsequent RT-qPCR and sequencing by Sanger or Nanopore whole genome sequencing (WGS). The method was successfully applied with different brands of SARS-CoV-2 Ag-RDTs, but also with Ag-RDTs for detection of influenza, rotavirus and adenovirus 40/41. The buffer used in the Ag-RDT had an important influence on the RNA yield from the test stripand the efficiency of subsequent sequencing. Our finding that the test strip in rapid Ag tests is suited to preserve viral genomic material, even for months at room temperature, and therefore can serve as source material for genetic characterization, could improve global coverage of genomic surveillance for SARS-CoV-2 as well as for other viruses.
HEART rate variability biofeedback for LOng Covid symptoms (HEARTLOC): protocol for a feasibility study
Authors: Corrado J , Halpin SJ , Preston N , Whiteside D , Tarrant R , Davison J , O’Connor RJ , Casson AJ , Sivan M 
Published: June 2022

AbstractIntroductionLong covid (LC), also known as Post-COVID-19 syndrome, refers to symptoms persisting 12 weeks after COVID-19 infection. It affects up to 1 in 7 people contracting the illness and causes a wide range of symptoms, including fatigue, breathlessness, palpitations, dizziness, pain and brain fog. Many of these symptoms can be linked to dysautonomia or dysregulation of the autonomic nervous system after SARS-CoV2 infection. This study aims to test the feasibility and estimate the efficacy, of the Heart Rate Variability Biofeedback (HRV-B) technique via a standardised slow diaphragmatic breathing programme in individuals with LC.Methods and Analysis30 adult LC patients with symptoms of palpitations or dizziness and an abnormal NASA Lean Test (NLT) will be selected from a specialist Long COVID rehabilitation service. They will undergo a 4-week HRV-B intervention using a Polar chest strap device linked to the Elite HRV phone application while undertaking the breathing exercise technique for two 10-min periods every day for at least 5 days a week. Quantitative data will be gathered during the study period using: HRV data from the chest strap and wrist-worn Fitbit, the modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm), composite autonomic symptom score (COMPASS 31), World Health Organisation Disability Assessment Schedule (WHODAS 2.0) and EQ-5D-5L health related quality of life measures. Qualitative feedback on user experience and feasibility of using the technology in a home setting will also be gathered. Standard statistical tests for correlation and significant difference will be used to analyse the quantitate data.Ethics and DisseminationThe study has received ethical approval from Health Research Authority (HRA) Leicester South Research Ethics Committee (21/EM/0271). Dissemination plans include academic and lay publications.Study RegistrationClinicaltrials.gov No: NCT05228665Strengths and limitations of the studyTo our knowledge, this is the first study of HRVB in long covid and will provide new information regarding the feasibility of the technology-based intervention in this condition.The estimation of efficacy will determine the scope and sample size for a larger controlled trial in the condition that currently has no definitive treatmentsThe study will provide preliminary evidence on the correlation between long covid symptoms and dysautonomia.The limitation of this study is the small sample size of 30 participants which might not give an accurate estimate of efficacy.HRV-B is a technology-based intervention, therefore its take-up could be limited in those with a lack of experience in using digital technology in daily life, particularly those from less privileged backgrounds.
AvP: a software package for automatic phylogenetic detection of candidate horizontal gene transfers
Authors: Koutsovoulos Georgios D. , Noriot Solène Granjeon , Bailly-Bechet Marc , Danchin Etienne G. J. , Rancurel Corinne 
Published: June 2022

AbstractHorizontal gene transfer (HGT) is the transfer of genes between species outside the transmission from parent to offspring. Due to their impact on the genome and biology of various species, HGTs have gained broader attention, but high-throughput methods to robustly identify them are lacking. One rapid method to identify HGT candidates is to calculate the difference in similarity between the most similar gene in closely related species and the most similar gene in distantly related species. Although metrics on similarity associated with taxonomic information can rapidly detect putative HGTs, these methods are hampered by false positives that are difficult to track. Furthermore, they do not inform on the evolutionary trajectory and events such as duplications. Hence, phylogenetic analysis is necessary to confirm HGT candidates and provide a more comprehensive view of their origin and evolutionary history. However, phylogenetic reconstruction requires several time-consuming manual steps to retrieve the homologous sequences, produce a multiple alignment, construct the phylogeny and analyze the topology to assess whether it supports the HGT hypothesis. Here, we present AvP which automatically performs all these steps and detects candidate HGTs within a phylogenetic framework.Availability and implementationAvP is written in Python and is available under GNU General Public License v3.0 at (https://github.com/GDKO/AvP).
Postsynaptic GluA3 subunits are required for the appropriate assembly of AMPA receptor GluA2 and GluA4 subunits on mammalian cochlear afferent synapses and for presynaptic ribbon modiolar-pillar morphological distinctions
Authors: Rutherford Mark A. , Bhattacharyya Atri , Xiao Maolei , Cai Hou Ming , Pal Indra , Rubio María E. 
Published: June 2022

AbstractThe encoding of acoustic signals in the cochlea depends on α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), but relatively little is known about their reliance on specific pore-forming subunits. With 5-week-old male GluA3KO mice, we determined cochlear function, synapse ultrastructure, and AMPAR subunit molecular anatomy at ribbon synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs). GluA3KO and wild-type (GluA3WT) mice reared in ambient sound pressure level (SPL) of 55-75 dB had similar ABR thresholds, wave-1 amplitudes, and latencies. Ultrastructurally, the IHC modiolar-pillar differences in presynaptic ribbon size and shape, and synaptic vesicle size seen in GluA3WT were diminished or reversed in GluA3KO. The quantity of paired synapses (presynaptic ribbons juxtaposed with postsynaptic GluA2 and GluA4) was similar, however, GluA2-lacking synapses (ribbons paired with GluA4 but not GluA2) were observed only in GluA3KO. SGNs of GluA3KO mice had AMPAR arrays of smaller overall volume, containing less GluA2 and greater GluA4 immunofluorescence intensity relative to GluA3WT (3-fold difference in mean GluA4:GluA2 ratio). The expected modiolar-pillar gradient in ribbon volume was observed in IHCs of GluA3WT but not GluA3KO. Unexpected modiolar-pillar gradients in GluA2 and GluA4 volume were present in GluA3KO. GluA3 is essential to the morphology and molecular composition of IHC-ribbon synapses. We propose the hearing loss seen in older male GluA3KO mice results from progressive synaptopathy evident in 5-week-old mice as increased abundance of GluA2-lacking, GluA4 monomeric, Ca2+-permeable AMPARs.
CHI3L1 enhances melanoma lung metastasis via regulation of t cell co-stimulators and CTLA-4/B7 axis
Authors: Ma Bing , Kamle Suchitra , Akosman Bedia , Khan Hina , Lee Chang Min , Lee Chun Geun , Elias Jack A. 
Published: June 2022

ABSTRACTICOS/ICOSL and CD28/B7-1/B7-2 are T cell co-stimulators and CTLA-4 is an immune checkpoint inhibitor that play critical roles in the pathogenesis of neoplasia. Chitinase 3-like-1 (CHI3L1) is induced in many cancers where it portends a poor prognosis and contributes to tumor metastasis. Here we demonstrate that CHI3L1 inhibits the expression of ICOS, ICOSL and CD28 while stimulating CTLA-4 and the B7 moieties in melanoma lung metastasis. We also demonstrate that RIG-like helicase innate immune activation augments T cell co-stimulation, inhibits CTLA-4 and suppresses pulmonary metastasis. At least additive antitumor responses were seen in melanoma lung metastasis treated with anti-CTLA-4 and anti-CHI3L1 antibodies in combination. Synergistic cytotoxic T cell-induced tumor cell death and the heightened induction of the tumor suppressor PTEN were seen in co-cultures of T and tumor cells treated with bispecific antibodies that target both CHI3L1 and CTLA-4. Thus, CHI3L1 contributes to pulmonary metastasis by inhibiting T cell co-stimulation and stimulating CTLA-4. The simultaneous targeting of CHI3L1 and the CTLA-4 axis with individual and, more powerfully with bispecific antibodies, represent promising therapeutic strategies for pulmonary metastasis.
To share or not to share? iEEG evidence for state-dependent inequity encoding in the human OFC
Authors: Marciano Deborah , Staveland Brooke R. , Lin Jack , Saez Ignacio , Hsu Ming , Knight Robert T. 
Published: June 2022

AbstractSocial decision-making requires the integration of reward valuation and social cognition systems, both dependent on the orbitofrontal cortex (OFC). How these two OFC functions interact is largely unknown. We recorded intracranial activity from the OFC of ten patients making choices in the context of different types of inequity (disadvantageous vs. advantageous). We found that high-frequency activity (70-150 HZ) encoded the amount of self-reward, consistent with previous reports. We also observed novel evidence for encoding in human OFC of the social counterpart’s reward as well as the type of inequity being experienced. Additionally, we find social context modulates reward encoding: depending on inequity type, reward encoding was switched on and off rapidly within electrodes, across trials. These results provide direct evidence for explicit encoding of self- and other- rewards in the human OFC, and for rapid and reversible changes in encoding schemes driven by socially relevant contexts.
ScanTecc classifies primary cancers via cell-free extrachromosomal circular DNA in peripheral blood
Authors: Fang Jingwen , Xu Yehong , Wang Jing , Shan Benjie , Ding Kaiyang , Li Shouzhen , Yu Qiaoni , Zhang Wen , Shao Yunying , Yang Jiaxuan , Liu Ke , Xu Guangtao , Yao Xinfeng , Sun Ruoming , Zhang Mengyuan , Zhang Zhihong , Pan Yueyin , Guo Chuang , Qu Kun 
Published: June 2022

ABSTRACTExtrachromosomal circular DNA (eccDNA) is gaining substantial attention in basic and clinical research for its contribution to tumor heterogeneity, biogenesis, and evolution. However, its presence and molecular features in peripheral blood from cancer patients are poorly understood. Here, we demonstrated the existence of eccDNA molecules in cancer patients’ plasma using atomic-force microscopy and high throughput sequencing technology. We then developed a method named ScanTecc (ScreeningcancerTypes with cell-freeeccDNA) that integrates cell-free circular DNA sequencing and machine learning approaches for cancer patient screening and classification. We applied ScanTecc on a total of 413 patients with multiple types of human primary cancers and 52 healthy individuals and found a significantly greater number and more extended size of eccDNAs in patients’ peripheral blood. ScanTecc accurately distinguished cancer patients (including early stages I and II) from healthy individuals with an overall prediction rate of 0.85 and identified distinct cancer types with an overall prediction rate of 0.84. Our study provides evidence for a non-invasive approach potentially applicable for early detection of cancer patients in clinics.
Factors Associated with Receipt and Parental Intent for COVID-19 Vaccination of Children Ages 5–11 years
Authors: Santibanez Tammy A. , Lendon Jessica Penn , Singleton James A. , Black Carla L. , Zhou Tianyi , Kriss Jennifer L. , Jain Anurag , Elam-Evans Laurie D. , Masters Nina B. , Peacock Georgina 
Published: June 2022

ABSTRACTBackground and ObjectivesCOVID-19 vaccine was first recommended for children ages 5–11 years on November 2, 2021. This report describes COVID-19 vaccination coverage and parental intent to vaccinate their child ages 5–11 years, overall, by sociodemographic characteristics, and by social and behavioral drivers of vaccination, the fourth month after recommendation.MethodsWe analyzed data from 5,438 interviews conducted in February 2022 from the National Immunization Survey-Child COVID Module (NIS-CCM), a national random-digit-dial cellular telephone survey of households with children.Results30.9% of children ages 5–11 were vaccinated with ≥1 dose of COVID-19 vaccine, 35.2% were unvaccinated and the parent reported they probably or definitely would get the child vaccinated or were unsure, and 33.9% were unvaccinated and the parent probably or definitely would not get the child vaccinated. Vaccination coverage and parental intent differed by sociodemographic variables, including income, health insurance status, and rurality. Parental intent to vaccinate children also differed by ethnicity and race. Concern about the child getting COVID-19 and confidence in vaccine importance and safety were positively associated with vaccination receipt and intent to get the child vaccinated.ConclusionsBy the fourth month of the COVID-19 vaccination program for children ages 5–11 years, less than one-third were vaccinated, and coverage was lower for some sociodemographic subgroups. An additional one-third of children had a parent who was open to vaccinating the child. Efforts to address parental concerns regarding vaccine safety and to convey the importance of the vaccine might improve vaccination coverage.