bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and Clinical Outcomes of Vaccine-Eligible US Children Under-5 Years Hospitalized for Acute COVID-19 in a National Network
Authors: Zambrano Laura D. , Newhams Margaret M. , Simeone Regina M. , Fleming-Dutra Katherine E. , Halasa Natasha , Wu Michael , Orzel-Lockwood Amber O. , Kamidani Satoshi , Pannaraj Pia S. , Chiotos Kathleen , Cameron Melissa A. , Maddux Aline B. , Schuster Jennifer E. , Crandall Hillary , Kong Michele , Nofziger Ryan A. , Staat Mary A. , Bhumbra Samina S. , Irby Katherine , Boom Julie A. , Sahni Leila C. , Hume Janet R. , Gertz Shira J. , Maamari Mia , Bowens Cindy , Levy Emily R. , Bradford Tamara T. , Walker Tracie C. , Schwartz Stephanie P. , Mack Elizabeth H. , Guzman-Cottrill Judith A. , Hobbs Charlotte V. , Zinter Matt S. , Cvijanovich Natalie Z. , Bline Katherine E. , Hymes Saul R. , Campbell Angela P. , Randolph Adrienne G. ,   for the Overcoming COVID-19 Investigators
Published: December 2023

Background and objectives:
In June 2022, the mRNA COVID-19 vaccination was recommended for young children. We examined clinical characteristics and factors associated with vaccination status among vaccine-eligible young children hospitalized for acute COVID-19.

Methods:
We enrolled inpatients 8 months to <5 years of age with acute community-acquired COVID-19 across 28 US pediatric hospitals from September 20, 2022 to May 31, 2023. We assessed demographic and clinical factors, including the highest level of respiratory support, and vaccination status defined as unvaccinated, incomplete, or complete primary series [at least 2 (Moderna) or 3 (Pfizer-BioNTech) mRNA vaccine doses ≥14 days before hospitalization].

Results:
Among 597 children, 174 (29.1%) patients were admitted to the intensive care unit and 75 (12.6%) had a life-threatening illness, including 51 (8.5%) requiring invasive mechanical ventilation. Children with underlying respiratory and neurologic/neuromuscular conditions more frequently received higher respiratory support. Only 4.5% of children hospitalized for COVID-19 (n = 27) had completed their primary COVID-19 vaccination series and 7.0% (n = 42) of children initiated but did not complete their primary series. Among 528 unvaccinated children, nearly half (n = 251) were previously healthy, 3 of them required extracorporeal membrane oxygenation for acute COVID-19 and 1 died.

Conclusions:
Most young children hospitalized for acute COVID-19, including most children admitted to the intensive care unit and with life-threatening illness, had not initiated COVID-19 vaccination despite being eligible. Nearly half of these children had no underlying conditions. Of the small percentage of children who initiated a COVID-19 primary series, most had not completed it before hospitalization.
Health financing in Sudan: key informant interviews in the wake of the 2023 conflict
Authors: Bashir Fatima , Allen Luke N 
Published: December 2023

AbstractBackgroundSudan is a large, landlocked, African country with a population of 46 million. It is considered a ‘least developed’ country, and coverage of essential health services is low. In April 2023 fighting broke out between the Sudanese Armed Forces and the paramilitary Rapid Support Forces. The conflict quickly escalated and has claimed 9,000 lives so far, with hundreds of thousands of people internally displaced. It is unclear exactly how the war has impacted Sudan’s already fragile health financing system.MethodsWe conducted one-to-one semi-structured interviews with a purposive sample of experienced health financing policymakers and policy advisors working in- or with the Sudanese government. Five senior key informants were recruited using snowball sampling. Interview transcripts were analysed using thematic analysis, with reference to the WHO national health financing framework and Sparkes and colleagues’ political economy framework.FindingsConflict has undoubtedly undermined Sudan’s ability to mobilise, allocate, and distribute financial resources. However, the existing health infrastructure was already so weak, and state funds so meagre, that the challenges posed by fighting were overshadowed by themes around Sudan’s underlying structural issues: out of pocket payments account for over 70% of all health expenditure; the existing national insurance scheme only covers a minority of the population; and there is unclear delineation of responsibilities between purchasers and providers and between the federal and state ministries of health. Major themes emerged around governance, revenue raising, risk pooling, purchasing and service delivery, and external donor funding.ConclusionsInvestment in developing health financing capacity at the state level, implementation planning, blended financing for the national health insurance fund, donor coordination, and community mobilisation to agitate for greater risk pooling were identified as essential steps. Without robust mechanisms to pool risk and diversification of financing sources, it will not be possible to extend financial risk protection or basic health services to large sections of Sudan’s population.
Annelid methylomes reveal ancestral developmental and ageing-associated epigenetic erosion across Bilateria
Authors: Guynes Kero , Sarre Luke A. , Carrillo-Baltodano Allan M. , Davies Billie E. , Xu Lan , Liang Yan , Martín-Zamora Francisco M. , Hurd Paul J. , de Mendoza Alex , Martín-Durán José M. 
Published: December 2023

AbstractBackgroundDNA methylation in the form of 5-methylcytosine (5mC) is the most abundant base modification in animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are hypermethylated, in most invertebrates, 5mC concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, in some species, on transposable elements (TEs), a pattern known as ‘mosaic’. Yet, the role and developmental dynamics of 5mC and how these explain interspecific differences in DNA methylation patterns remain poorly understood, especially in Spiralia, a large clade of invertebrates comprising nearly half of the animal phyla.ResultsHere, we generate base-resolution methylomes for three species with distinct genomic features and phylogenetic positions in Annelida, a major spiralian phylum. All possible 5mC patterns occur in annelids, from typical invertebrate intermediate levels in a mosaic distribution to hypermethylation and methylation loss. GbM is common to annelids with 5mC, and methylation differences across species are explained by taxon-specific transcriptional dynamics or the presence of intronic TEs. Notably, the link between GbM and transcription decays during development, and there is a gradual and global, age-dependent demethylation in adult stages. Moreover, reducing 5mC levels with cytidine analogues during early development impairs normal embryogenesis and reactivates TEs in the annelidOwenia fusiformis.ConclusionsOur study indicates that global epigenetic erosion during development and ageing is an ancestral feature of bilateral animals. However, the tight link between transcription and gene body methylation is likely important in early embryonic stages, and 5mC-mediated TE silencing probably emerged convergently across animal lineages.
Lipid peroxidation does not mediate muscle atrophy induced by PSD deficiency
Authors: Eshima Hiroaki , Johnson Jordan M. , Funai Katsuhiko 
Published: December 2023

AbstractMechanisms by which disuse promotes skeletal muscle atrophy is not well understood. We previously demonstrated that disuse reduces the abundance of mitochondrial phosphatidylethanolamine (PE) in skeletal muscle. Deletion of phosphatidylserine decarboxylase (PSD), an enzyme that generates mitochondrial PE, was sufficient to promote muscle atrophy. In this study, we tested the hypothesis that muscle atrophy induced by PSD deletion is driven by an accumulation of lipid hydroperoxides (LOOH). Mice with muscle-specific knockout of PSD (PSD-MKO) were crossed with glutathione peroxidase 4 (GPx4) transgenic mice (GPx4Tg) to suppress the accumulation of LOOH. However, PSD-MKO x GPx4Tg mice and PSD-MKO mice demonstrated equally robust loss of muscle mass. These results suggest that muscle atrophy induced by PSD deficiency is not driven by the accumulation of LOOH.
Ppx1 putative exopolyphosphatase is essential for polyphosphate accumulation inLacticaseibacillus paracasei
Authors: Corrales Daniela , Alcántara Cristina , Zúñiga Manuel , Monedero Vicente 
Published: December 2023

ABSTRACTThe linear polymer polyphosphate (poly-P) is present across all three domains of life and serves diverse physiological functions. The enzyme polyphosphate kinase (Ppk) is responsible for poly-P synthesis, whereas poly-P degradation is carried out by the enzyme exopolyphosphatase (Ppx). In manyLactobacillaceae, the Ppk-encoding gene (ppk) is found clustered together with two genes encoding putative exopolyphosphatases (ppx1andppx2) each having different domain compositions, with the gene orderppx1-ppk-ppx2. However, the specific function of theseppxgenes remains unexplored. An in-frame deletion ofppx1inLacticaseibacillus paracaseiBL23 resulted in bacteria unable to accumulate poly-P, whereas disruption ofppx2had no effect on poly-P synthesis. Expression ofppkwas not altered in the Δppx1strain, and poly-P synthesis in this strain was only restored by expressingppx1intrans. Moreover, no poly-P synthesis was observed whenppkwas expressed from a plasmid in the Δppx1strain. Purified Ppx2 exhibitedin vitroexopolyphosphatase activity, whereas noin vitroenzymatic activity could be demonstrated for Ppx1. This observation corresponds with the absence in Ppx1 of conserved motifs essential for catalysis found in characterized exopolyphosphatases. Furthermore, assays with purified Ppk and Ppx1 evidenced that Ppx1 enhanced Ppk activity. These results demonstrate that Ppx1 is essential for poly-P synthesis inLc. paracaseiand have unveiled, for the first time, an unexpected role of Ppx1 exopolyphosphatase in poly-P synthesis.ImportancePoly-P is a pivotal molecular player in bacteria, participating in a diverse array of processes ranging from stress resilience to pathogenesis, while also serving as a functional component in probiotic bacteria. The synthesis of poly-P is tightly regulated, but the underlying mechanisms remain incompletely elucidated. Our study sheds light on the distinctive role played by the two exopolyphosphatases (Ppx) found in theLactobacillaceaebacterial group, of relevance in food and health. This particular group is noteworthy for possessing two Ppx enzymes, supposedly involved in poly-P degradation. Remarkably, our investigation uncovers an unprecedented function of Ppx1 inLacticaseibacillus paracasei, where its absence leads to the total cessation of poly-P synthesis, paralleling the impact observed upon eliminating the poly-P forming enzyme, poly-P kinase. Unlike the anticipated role as a conventional exopolyphosphatase, Ppx1 demonstrates an unexpected function. Our results added a layer of complexity to our understanding of poly-P dynamics in bacteria.
One million years of solitude: the rapid evolution of de novo protein structure and complex
Authors: Chen Jianhai , Li Qingrong , Xia Shengqian , Arsala Deanna , Sosa Dylan , Wang Dong , Long Manyuan 
Published: December 2023

AbstractRecent studies have established that de novo genes, evolving from non-coding sequences, enhance protein diversity through a stepwise process. However, the pattern and rate of their structural evolution over time remain unclear. Here, we addressed these issues within a short evolutionary timeframe (∼1 million years for 97% of rice de novo genes). We found that de novo genes evolve faster than gene duplicates in the intrinsic disordered regions (IDRs, such as random coils), secondary structural elements (such as α-helix and β-strand), hydrophobicity, and molecular recognition features (MoRFs). Specifically, we observed an 8-14% decay in random coils and IDR lengths per million years per protein, and a 2.3-6.5% increase in structured elements, hydrophobicity, and MoRFs. These patterns of structural evolution align with changes in amino acid composition over time. We also revealed significantly higher positive charges but smaller molecular weights for de novo proteins than duplicates. Tertiary structure predictions demonstrated that most de novo proteins, though not typically well-folded on their own, readily form low-energy and compact complexes with extensive residue contacts and conformational flexibility, suggesting “a faster-binding” scenario in de novo proteins to promote interaction. Our findings illuminate the rapid evolution of protein structure in the early life of de novo proteins in rice genome, originating from noncoding sequences, highlighting their quick transformation into active, complex-forming components within a remarkably short evolutionary timeframe.
Spatial dissection of cellular heterogeneity and functional crosstalk in the tumor microenvironments of gastric cancers
Authors: Lee Sung Hak , Lee Dagyeong , Choi Junyong , Oh Hye Jeong , Ham In-Hye , Ryu Daeun , Lee Seo-Yeong , Han Dong-Jin , Kim Sunmin , Lee Seungho , Hur Hoon , Kim Tae-Min 
Published: December 2023

AbstractSpatial transcriptomics offers unprecedented challenges in characterizing tumor ecosystems, encompassing tumor cells and their surrounding tumor microenvironments (TME) along with cellular interactions therein. Here, we conducted Visium-based spatial transcriptomics on nine primary gastric cancers (GC) to translate the spatial organization of GC ecosystems into the functional landscape of cellular crosstalk across malignant, stromal and immune cells. We identified three distinct GC subtypes of 3 immunogenic, 3 epithelial and 3 stromal GCs with elevated infiltration of immune, malignant cells and fibroblasts reflecting the heterogeneity of the cell types and their interactions in GC TME. GC spatial architecture was further delineated into 6 regional compartments with varying degree of TME infiltration, among which the fibroblast-enriched TME was associated with the upregulation of epithelial-to-mesenchymal transformation (EMT) and immune response in malignant and immune cells, respectively. Cell type-specific transcriptional dynamics representing cellular crosstalk between TME cells were further identified, e.g., the infiltration of malignant and endothelial cells promote the cellular proliferations of TME cells whereas the fibroblasts and immune cells are associated with pro-cancer and anti-cancer immunity, respectively. Ligand-receptor analysis further revealed thatCCL2-expressing fibroblasts promote the pro-cancer signaling of immune cells including JAK-STAT3 signaling and inflammatory response in tumor-infiltration macrophages. TheCCL2+fibroblasts and macrophages with activated JAK-STAT3 signals are co-localized in spatial GC architecture and their co-abundance was associated with unfavorable clinical outcomes. Taken together, GC spatial transcriptomes can be regionally and functionally delineated into functional cellular crosstalk involving multiple cell types with potential clinical relevance, particularly the interaction betweenCCL2+fibroblasts and JAK-STAT3+macrophages contributing to cancer-favoring immune contexture in GC TME.
CentIER: accurate centromere identification for plant genomes with sequence specificity information
Authors: Xu Dong , Wen Huaming , Feng Wenle , Zhang Xiaohui , Hui Xingqi , Xu Yun , Chen Fei , Pan Weihua 
Published: December 2023

AbstractCentromere identification is one of the important problems in genomics, providing a foundation for the studies of centromeres in aspects of composition, functionality, evolution, inheritance, and variation. The existing wet-experiment-based method is costly and time-consuming, while the bioinformatic method can only detect tandem repeats losing non-repetitive sequence regions in the centromere. To address these shortcomings, we introduce a new pipeline, CentIER, for the automatic and accurate identification and annotation of centromere regions by taking advantage of the sequence specificity information. CentIER only requires users to input the genomic sequence, and then it can partition the centromeric region from a chromosome, identify tandem repeat monomers, annotate retrotransposons, and ultimately output visualized results. By referencing the experimentally determined centromere regions, it was discovered that the predictive accuracy of centromere recognition by CentIER exceeded 90%. Following the evaluation of CentIER’s accuracy, it was applied to investigate the sequence and distribution characteristics of centromeric retrotransposons and tandem repeat sequences of different species, providing insights into these traits in monocotyledonous and dicotyledonous plants.
Mapping adipocyte interactome networks by Halotag-enrichment-mass spectrometry
Authors: Yazaki Junshi , Yamanashi Takashi , Nemoto Shino , Kobayashi Atsuo , Han Yong-Woon , Hasegawa Tomoko , Iwase Akira , Ishikawa Masaki , Konno Ryo , Imami Koshi , Kawashima Yusuke , Seita Jun 
Published: December 2023

ABSTRACTMapping protein interaction complexes in their natural statein vivorepresents the holy grail of protein network analysis. Detection of protein interaction stoichiometry has been an important technical challenge, as few studies have focused this, yet this may be solved by artificial intelligence and proteomics. Here, we describe the development of HaloMS, a high-throughput HaloTag-based affinity purification–mass spectrometry assay for protein interaction discovery. The approach enables the rapid capture of newly expressed proteins, eliminating tedious conventional one-by-one assay. As a proof-of-principle, we used HaloMS to evaluate protein complex interactions of 17 regulatory proteins in human adipocytes. The adipocyte interactome network was validated using anin vitropull-down assay and artificial intelligence-based prediction tools. The application of HaloMS to probe adipocyte differentiation facilitated the identification of previously unknown transcription factor–protein complexes, revealing proteome-wide human adipocyte transcription factor networks, and shedding light on how different pathways are integrated.
De-novogenome assembly of four rails (Aves: Rallidae): a resource for comparative genomics
Authors: Gaspar Julien , Trewick Steve A. , Gibb Gillian C. 
Published: December 2023

AbstractThe rails are a phenotypically diverse family of birds that includes around 130 species and displays a wide distribution around the world. Here we present annotated genome assemblies for four rails from Aotearoa New Zealand: two native volant species, pūkekoPorphyrio melanotusand miowekaGallirallus philippensis, and two endemic flightless species takahēPorphyrio hochstetteriand wekaGallirallus australis. The quality checks and comparison with other rallid genomes showed that the new assemblies were of high quality and that the annotations could be trusted. Using the sequence read data, heterozygosity was found to be lowest in the endemic flightless species and this probably reflects their relatively small populations. This study significantly increases the number of available rallid genomes and will enable future genomic studies on the evolution of this family.
Embryo-restricted responses to maternal IL-17A promote neurodevelopmental disorders in mouse offspring
Authors: Andruszewski David , Uhlfelder David C. , Desiato Genni , Regen Tommy , Schelmbauer Carsten , Blanfeld Michaela , Scherer Lena , Radyushkin Konstantin , Pozzi Davide , Waisman Ari , Mufazalov Ilgiz A. 
Published: December 2023

AbstractPrenatal imprinting to interleukin 17A (IL-17A) triggers behavioral disorders in offspring. However, reported models of maternal immune activation utilizing immunostimulants, lack specificity to elucidate the anatomical compartments of IL-17A’s action and the distinct behavioral disturbances it causes. By combining transgenic IL-17A overexpression with maternal deficiency in its receptor, we established a novel model of prenatal imprinting to maternal IL-17A (acronym: PRIMA-17 model). This model allowed us to study prenatal imprinting established exclusively through embryo-restricted IL-17A responses. We demonstrated IL-17A transfer across the placental barrier and subsequent development of selected behavioral deficits in mouse offspring. More specifically, embryonic responses to IL-17A resulted in communicative impairment in early-life measured by reduced numbers of nest retrieval calls. In adulthood, IL-17A-imprinted offspring displayed an increase in anxiety-like behavior. We advocate our PRIMA-17 model as a useful tool to study neurological deficits in mice.
Gene expression response to temperature acclimation in a model photoheterotrophic marine flavobacterium (Dokdoniasp. MED134)
Authors: Robaina-Estévez Semidán , González José M. , María Cabello Ana , Palacio Antonio S. , Gallagher Ruairí , López-Urrutia Ángel , Alonso-Sáez Laura 
Published: December 2023

ABSTRACTTemperature stands as one of the key factors influencing the community structure and distribution of marine microorganisms. Yet, the physiological adaptations of marine bacteria to rising temperatures remain underexplored. This study examines the transcriptional response ofDokdoniasp. MED134, a proteorhodopsin-based phototrophic organism within the classFlavobacteriia, to a gradient of temperature acclimation conditions from 10 to 34°C. Light availability during day/night cycles exerted minimal influence on the transcriptional patterns of this strain, with only a few genes mostly related to light sensing, light protecting mechanisms and phototrophy being upregulated during daytime. By contrast, temperature significantly impacted the expression of a large fraction of MED134 genes (>60%), including components of the stress response, cellular translation, DNA replication, and some metabolic pathways such as the anaplerotic carbon fixation and the glyoxylate shunt, suggesting intracellular carbon flow adjustments to temperature. Notably, the expression of some highly expressed TonB transporters, prominent in flavobacteria, was also temperature-sensitive. Our findings provide insights into the transcriptional adjustments ofDokdoniasp. MED134 in response to temperature variations, suggesting potential implications for carbon cycling and organic matter processing in marine environments.