bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wealth Effects of the Decrease in Under-five Mortality in India, 2005-2021
Authors: Chaurasia Aalok Ranjan 
Published: April 2023

AbstractThe present paper analyses the contribution of different population sub-groups classified by the wealth index quantiles groups to the change in the risk of death in the first five years of life in India during 2005-06 through 2019-21. The analysis reveals that the poorest and the poorer population sub-groups have primarily contributed to the decrease in the risk of death in the first five years of life in India whereas the contribution of the contribution of the richest population sub-group has been negative during the period under reference. The analysis also reveals that the wealth effects of the decrease in under-five mortality in different states of the country are different and, in many states, the contribution of the richest population sub-group to the decrease in the risk of death in the first five years of life in the state has been negative because of the change in the proportionate share of currently married women of reproductive age across different population sub-groups and their fertility. The paper emphasises the need of reinvigorating the health care services delivery system of the country so as to prevent under five deaths which cannot be prevented through the low-cost appropriate medical technology.
Effectiveness of mRNA COVID-19 monovalent and bivalent vaccine booster doses against Omicron severe outcomes among adults aged ≥50 years in Ontario, Canada
Authors: Grewal Ramandip , Buchan Sarah A , Nguyen Lena , Nasreen Sharifa , Austin Peter C. , Brown Kevin A. , Gubbay Jonathan , Lee Nelson , Schwartz Kevin L , Tadrous Mina , Wilson Kumanan , Wilson Sarah E , Kwong Jeffrey C 
Published: April 2023

ABSTRACTObjectiveWe estimated the effectiveness of booster doses of monovalent and bivalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults aged ≥50 years in Ontario, Canada.MethodsWe used a test-negative design to estimate vaccine effectiveness (VE), with unvaccinated adults as the comparator, against hospitalization or death among SARS-CoV-2-tested adults aged ≥50 years between June 19, 2022 and January 28, 2023 stratified by time since vaccination. We explored VE by vaccine product (Moderna Spikevax®monovalent; Pfizer-BioNTech Comirnaty®monovalent; Moderna Spikevax®BA.1 bivalent; Pfizer-BioNTech Comirnaty®BA.4/BA.5 bivalent).ResultsWe included 3,755 Omicron cases and 14,338 test-negative controls. For the Moderna and Pfizer-BioNTech monovalent vaccines, VE 7-29 days after vaccination was 85% (95% confidence interval [CI], 72-92%) and 88% (95%CI, 82-92%), respectively, and was 82% (95%CI, 76-87%) and 82% (95%CI, 77-86%) 90-119 days after vaccination. For the Moderna BA.1 bivalent vaccine, VE was 86% (95%CI, 82-90%) 7-29 days after vaccination and was 76% (95%CI, 66-83%) 90-119 days after vaccination. For the Pfizer-BioNTech BA.4/BA.5 bivalent vaccine, VE 7-29 days after vaccination was 83% (95%CI, 77-88%) and was 81% (95%CI 72-87%) 60-89 days after vaccination.ConclusionsBooster doses of monovalent and bivalent mRNA COVID-19 vaccines provided similar, strong initial protection against severe outcomes in community-dwelling adults aged ≥50 years in Ontario. Nonetheless, uncertainty remains around waning protection of these vaccines.
A methodological framework for assessing the benefit of SARS-CoV-2 vaccination following previous infection: case study of five to eleven year olds
Authors: Pagel Christina , Wilde Harrison , Tomlinson Christopher , Mateen Bilal , Brown Katherine 
Published: April 2023

AbstractVaccination rates against SARS-CoV-2 in children aged five to 11 years remain low in many countries. The current benefit of vaccination in this age group has been questioned given that the large majority of children have now experienced at least one SARS-CoV-2 infection. However, protection from infection, vaccination or both wanes over time. National decisions on offering vaccines to this age group have tended to be made without considering time since infection.There is an urgent need to evaluate the additional benefits of vaccination in previously infected children and under what circumstances those benefits accrue. We present a novel methodological framework for estimating the potential benefits of COVID-19 vaccination in previously infected children aged five to 11, accounting for waning. We apply this framework to the UK context and for two adverse outcomes: hospitalisation related to SARS-CoV-2 infection and Long Covid.We show that the most important drivers of benefit are: the degree of protection provided by previous infection; the protection provided by vaccination; the time since previous infection; and future attack rates. Vaccination can be very beneficial for previously infected children if future attack rates are high and several months have elapsed since the previous major wave in this group. Benefits are generally larger for Long Covid than hospitalisation, because Long Covid is both more common than hospitalisation and previous infection offers less protection against it.Our framework provides a structure for policy makers to explore the additional benefit of vaccination across a range of adverse outcomes and different parameter assumptions. It can be easily updated as new evidence emerges.
Alignment of spatial transcriptomics data using diffeomorphic metric mapping
Authors: Clifton Kalen , Anant Manjari , Aihara Gohta , Atta Lyla , Aimiuwu Osagie K. , Kebschull Justus M. , Miller Michael I. , Tward Daniel , Fan Jean 
Published: April 2023

AbstractSpatial transcriptomics (ST) technologies enable high throughput gene expression characterization within thin tissue sections. However, comparing spatial observations across sections, samples, and technologies remains challenging. To address this challenge, we developed STalign to align ST datasets in a manner that accounts for partially matched tissue sections and other local non-linear distortions using diffeomorphic metric mapping. We apply STalign to align ST datasets within and across technologies as well as to align ST datasets to a 3D common coordinate framework. We show that STalign achieves high gene expression and cell-type correspondence across matched spatial locations that is significantly improved over landmark-based affine alignments. Applying STalign to align ST datasets of the mouse brain to the 3D common coordinate framework from the Allen Brain Atlas, we highlight how STalign can be used to lift over brain region annotations and enable the interrogation of compositional heterogeneity across anatomical structures. STalign is available as an open-source Python toolkit athttps://github.com/JEFworks-Lab/STalignand as supplementary software with additional documentation and tutorials available athttps://jef.works/STalign.
RTEL1 is required for silencing and epigenome stability
Authors: Olivier Margaux , Hesketh Amy , Pouch-Pélissier Marie-Noëlle , Pélissier Thierry , Huang Ying , Latrasse David , Benhamed Moussa , Mathieu Olivier 
Published: April 2023

AbstractTranscriptional silencing is an essential mechanism for controlling the expression of genes, transgenes and heterochromatic repeats through specific epigenetic marks on chromatin that are maintained during DNA replication. In Arabidopsis, silenced transgenes and heterochromatic sequences are typically associated with high levels of DNA methylation, while silenced genes are enriched in H3K27me3. Reactivation of these loci is often correlated with decreased levels of these repressive epigenetic marks. Here, we report that the DNA helicase REGULATOR OF TELOMERE ELONGATION 1 (RTEL1) is required for transcriptional silencing. RTEL1 deficiency causes upregulation of many genes enriched in H3K27me3 accompanied by a moderate decrease in this mark, but no loss of DNA methylation at reactivated heterochromatic loci. Instead, heterochromatin exhibits DNA hypermethylation and increased H3K27me3 inrtel1. We further find that loss of RTEL1 suppresses the release of heterochromatin silencing caused by the absence of the MOM1 silencing factor. RTEL1 is conserved among eukaryotes and plays a key role in resolving DNA secondary structures during DNA replication. Inducing such aberrant DNA structures using DNA cross-linking agents also results in a loss of transcriptional silencing. These findings uncover unappreciated roles for RTEL1 in transcriptional silencing and in stabilizing DNA methylation and H3K27me3 patterns.
Terminal type-specific cannabinoid CB1 receptor alterations in patients with schizophrenia: a pilot study
Authors: Chou Shinnyi , Fish Kenneth N , Lewis David A , Sweet Robert A 
Published: April 2023

AbstractBackgroundIndividuals with schizophrenia are at elevated genetic risks for comorbid cannabis use, and often experience exacerbations of cognitive and psychotic symptoms when exposed to cannabis. These findings have led a number of investigators to examine cannabinoid CB1 receptor (CB1R) alterations in schizophrenia, though with conflicting results. We recently demonstrated the presence of CB1R in both excitatory and inhibitory boutons in the human prefrontal cortex, with differential levels of the receptor between bouton types. We hypothesized that the differential enrichment of CB1R between bouton types – a factor previously unaccounted for when examining CB1R changes in schizophrenia – may resolve prior discrepant reports and increase our insight into the effects of CB1R alterations on the pathophysiology of schizophrenia.MethodsUsing co-labeling immunohistochemistry and fluorescent microscopy, we examined total CB1R levels and CB1R levels within excitatory (vGlut1-positive) and inhibitory (vGAT-positive) boutons of prefrontal cortex samples from ten pairs of individuals diagnosed with schizophrenia and non-psychiatric comparisons.ResultsSignificantly higher total CB1R levels were found within samples from individuals with schizophrenia. Terminal type-specific analyses identified significantly higher CB1R levels within excitatory boutons in samples from individuals with schizophrenia relative to comparisons. In contrast, CB1R levels within the subset of inhibitory boutons that normally express high CB1R levels (presumptive cholecystokinin neuron boutons) were lower in samples from individuals with schizophrenia relative to comparison samples.ConclusionGiven CB1R’s role in suppressing neurotransmission upon activation, these results suggest an overall shift in excitatory and inhibitory balance regulation toward a net reduction of excitatory activity in schizophrenia.
SpatialCTD: a large-scale TME spatial transcriptomic dataset to evaluate cell type deconvolution for immuno-oncology
Authors: Ding Jiayuan , Venegas Julian , Lu Qiaolin , Wang Yixin , Wu Lidan , Jin Wei , Wen Hongzhi , Liu Renming , Tang Wenzhuo , Li Zhaoheng , Zuo Wangyang , Chang Yi , Lei Yu Leo , Danaher Patrick , Xie Yuying , Tang Jiliang 
Published: April 2023

AbstractRecent technological advancements have enabled spatially resolved transcriptomic profiling but at multi-cellular resolution. The task of cell type deconvolution has been introduced to disentangle discrete cell types from such multi-cellular spots. However, existing datasets for cell type deconvolution are limited in scale, predominantly encompassing data on mice, and are not designed for human immuno-oncology. In order to overcome these limitations and promote comprehensive investigation of cell type deconvolution for human immuno-oncology, we introduce a large-scale spatial transcriptomic dataset named SpatialCTD, encompassing 1.8 million cells from the human tumor microenvironment across the lung, kidney, and liver. Distinct from existing approaches that primarily depend on single-cell RNA sequencing data as a reference without incorporating spatial information, we introduce Graph Neural Network-based method (i.e., GNNDeconvolver) that effectively utilize the spatial information from reference samples, and extensive experiments show that GNNDeconvolveroften outperforms existing state-of-the-art methods by a substantial margin, without requiring single-cell RNA-seq data. To enable comprehensive evaluations on spatial transcriptomics data from flexible protocols, we provide an online tool capable of converting spatial transcriptomic data from other platforms (e.g., 10x Visium, MERFISH and sci-Space) into pseudo spots, featuring adjustable spot size. The SpatialCTD dataset and GNNDeconvolverimplementation are available athttps://github.com/OmicsML/SpatialCTD, and the online converter tool can be accessed athttps://omicsml.github.io/SpatialCTD/.
ARDitox: platform for the prediction of TCRs potential off-target binding
Authors: Pienkowski Victor Murcia , Boschert Tamara , Skoczylas Piotr , Sanecka-Duin Anna , Jasiński Maciej , Król-Józaga Bartłomiej , Mazzocco Giovanni , Stachura Sławomir , Bunse Lukas , Kaczmarczyk Jan , Green Edward W , Blum Agnieszka 
Published: April 2023

AbstractCellular immunotherapies, such as those utilizing T lymphocytes expressing native or engineered T cell receptors (TCRs), have already demonstrated therapeutic efficacy. However, some high-affinity TCRs have also proved to be fatal due to off-target immunotoxicity. This process occurs when the immune system acts against epitopes found on both tumor cells and healthy tissues. Moreover, some TCRs can be cross-reactive to epitopes with highly dissimilar sequences. To address this issue, we developed ARDitox, a novelin silicomethod based on computational immunology and artificial intelligence (AI) for predicting and analyzing potential off-target binding. We tested the performance of ARDitoxin silicoon different cases found in the literature where TCRs were used to target cancer-related antigens, as well as on a set of TCRs targeting a viral epitope. ARDitox was able to identify previously reported cross-reactive epitopes in line with the data available in the literature. In addition, we investigated a TCR targeting an HLA-A*02:01-restricted immunodominant epitope from the glioblastoma-associated antigen NLGN4X, identifying a cross-reactive ADH1A epitope that would not be detected in murine models. In conclusion, ourin silicoapproach is a powerful tool that identifies potential off-target epitopes, complementing preclinical studies in developing safer cell therapies targeting tumor(- associated) antigens.
Retrovirus-Like Gag Protein Arc/Arg3.1 is Involved in Extracellular-Vesicle-Mediated mRNA Transfer between Glioma Cells
Authors: Othman Aya Al , Bagrov Dmitry , Rozenberg Julian M , Glazova Olga , Skryabin Gleb , Tchevkina Elena , Mezentsev Alexandre , Durymanov Mikhail 
Published: April 2023

ABSTRACTActivity-regulated cytoskeleton-associated (Arc) protein is expressed in neural tissue of vertebrates, where it plays a pivotal role in modulation of synaptic communication. In addition, Arc protein forms capsid-like particles, which can encapsulate and transfer mRNA in extracellular vesicles (EVs) between neurons, that could modulate synaptic function and plasticity. Glioma cell networks actively interact with neuronsviaparacrine signaling and formation of neurogliomal glutamatergic synapses that contribute to cancer cell survival, proliferation, and invasion. Here, we revealed that Arc is expressed in human glioma cell lines, which can produce EVs containing Arc protein andArcmRNA (or “Arc EVs”). Recombinant Arc protein binds toArcmRNA with 1.5-fold higher affinity as compared with controlmCherrymRNA. Arc EVs from U87 glioma cells internalize and deliverArcmRNA to recipient U87 cells, where it is translated into a protein. Arc overexpression significantly increases EV production, alters EV morphology, and enhances intercellular transfer of highly expressed mRNA in glioma cell culture. These findings indicate involvement of Arc EVs into mRNA transfer between glioma cells that could contribute to tumor progression and affect synaptic plasticity in cancer patients.
Erythroid differentiation intensifies RNA mis-splicing inSF3B1-mutant myelodysplastic syndromes with ring sideroblasts
Authors: Moura Pedro L. , Mortera-Blanco Teresa , Hofman Isabel J.F. , Todisco Gabriele , Kretzschmar Warren W. , Björklund Ann-Charlotte , Creignou Maria , Hagemann-Jensen Michael , Ziegenhain Christoph , Granados David C. , Barbosa Indira , Walldin Gunilla , Jansson Monika , Ashley Neil , Mead Adam J. , Lundin Vanessa , Dimitriou Marios , Yoshizato Tetsuichi , Woll Petter S. , Ogawa Seishi , Sandberg Rickard , Jacobsen Sten Eirik W. , Hellström-Lindberg Eva 
Published: April 2023

AbstractMyelodysplastic syndromes with ring sideroblasts (MDS-RS) commonly originate from mutations in the splicing factorSF3B1(SF3B1mt).SF3B1mtcause RNA mis-splicing, mechanistically established as the major driver of RS development. However, little is known about RS fate and biology after their initial formation in the human bone marrow. We here achieve isolation of viable RS from patient samples, enabling the first complete investigation ofSF3B1mtdevelopment from stem cell to RS. We show that RS skew MACS-isolated CD34+data towards erythroid features not recapitulated in single-cell RNAseq. We demonstrate that RS divide, differentiate, enucleate and actively respond to mis-splicing/oxidative stress, decreasing wildtype stem cell fitness via GDF15 overproduction. We identify circulating RS as a uniform clinical feature associated with disease burden. Finally, we establish thatSF3B1mtmis-splicing intensifies during erythroid differentiation and demonstrate through combined transcriptomics/proteomics an uncoupling of RNA/protein biology in RS encompassing severe and dysfunctional mis-splicing of proapoptotic genes.Statement of significanceWe here combine a novel method for RS isolation with state-of-the-art multiomics to perform the first complete investigation ofSF3B1mtMDS-RS hematopoiesis from stem cell to RS. We identify the survival mechanisms underlyingSF3B1mterythropoiesis and establish an active role for erythroid differentiation and RS themselves inSF3B1mtMDS-RS pathogenesis.
PITAR, a DNA damage-inducible Cancer/Testis long noncoding RNA, inactivates p53 by binding and stabilizing TRIM28 mRNA
Authors: Jana Samarjit , Mondal Mainak , Mahale Sagar , Gupta Bhavana , Prasasvi Kaval Reddy , Kandasami Lekha , Jha Neha , Chowdhury Abhishek , Santosh Vani , Kanduri Chandrasekhar , Somasundaram Kumaravel 
Published: April 2023

AbstractIn tumors with WT p53, alternate mechanisms of p53 inactivation are reported. Here, we have identified a long noncoding RNA, PITAR (p53InactivatingTRIM28associatedRNA), as an inhibitor of p53. PITAR is an oncogenic Cancer/testis lncRNA and is highly expressed in glioblastoma (GBM) and glioma stem-like cells (GSC). We establish that TRIM28 mRNA, which encodes a p53-specific E3 ubiquitin ligase, is a direct target of PITAR. PITAR interaction with TRIM28 RNA stabilized TRIM28 mRNA, which resulted in increased TRIM28 protein levels and reduced p53 steady-state levels due to enhanced p53 ubiquitination. DNA damage activated PITAR, in addition to p53, in a p53-independent manner, thus creating an incoherent feedforward loop to inhibit the DNA damage response by p53. While PITAR silencing inhibited the growth of WT p53 containing GSCs in vitro and reduced glioma tumor growth in vivo, its overexpression enhanced the tumor growth in a TRIM28-dependent manner and promoted resistance to Temozolomide. Thus, we establish an alternate way of p53 inactivation by PITAR, which maintains low p53 levels in normal cells and attenuates the DNA damage response by p53. Finally, we propose PITAR as a potential GBM therapeutic target.
Tr1 cell-mediated protection against autoimmune disease by intranasal administration of a fusion protein targeting cDC1 cells
Authors: Hansson Charlotta , Lebrero-Fernández Cristina , Schön Karin , Angeletti Davide , Lycke Nils 
Published: April 2023

ABSTRACTCurative therapies against autoimmune diseases are lacking. Indeed, most of currently available treatments are only targeting symptoms. We have developed a novel strategy for a therapeutic vaccine against autoimmune diseases based on intranasal administration of a fusion protein tolerogen, which consists of a mutant, enzymatically inactive, cholera toxin A1-subunit genetically fused to disease relevant high affinity peptides and a dimer of D-fragments from protein A. The CTA1R7K-MOG/PLP-DD fusion proteins effectively reduced clinical symptoms in the experimental autoimmune encephalitis (EAE)-model of multiple sclerosis (MS). The treatment induced Tr1 cells, in the draining lymph node, which produced IL-10 and suppressed effector CD4+T cell responses. This effect was dependent on IL-27 signalling, since treatment was ineffective in bone marrow chimeras lacking IL-27Rα within their hematopoietic compartment. scRNA-seq of dendritic cells (DC) in draining lymph nodes demonstrated distinct gene transcriptional changes of cDC1, including enhanced lipid metabolic pathways, induced by the tolerogenic fusion protein. Thus, our results with the tolerogenic fusion protein demonstrates the possibility to vaccinate and protect against disease progression by reinstating tolerance in MS and other autoimmune diseases.
In depth amino acid mutational analysis of the key interspecific incompatibility transmembrane factor Stigmatic Privacy 1
Authors: Kato Yoshinobu , Tadokoro Shun , Ishida Shota , Niidome Maki , Kimura Yuka , Takayama Seiji , Fujii Sota 
Published: April 2023

SummaryIn plants, there is an active prezygotic interspecific-incompatibility mechanism to prevent unfavorable hybrids between two species. We previously reported that an uncharacterized protein with four-transmembrane domains, named as Stigmatic Privacy 1 (SPRI1), is responsible for rejecting hetero-specific pollen grains inArabidopsis thaliana.We have conducted a functional study of the SPRI1 protein, via point-mutational experiments and biochemical analysis. We studied the molecular regulatory mechanisms of SPRI1 and the relationships with its function.The alanine- and glycine-scanning experiments together with the evolutional analysis showed that the structural integrity of the C-terminal regions of the extracellular domain of this protein is important for its function. In addition, we found two cysteines (C67 and C80) within the extracellular domain that may be involved in the formation of intermolecular disulfide bonds. SPRI1 may form homo-multimers and is present as part of a ca. 300 kDa complex.Our present study indicates that molecular complex formation ability of SPRI1 may be important to maintain its stability and interspecific incompatibility functions in cells.