bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges in the Diagnosis of Epstein-Barr Virus-positive Inflammatory Follicular Dendritic Cell Sarcoma
Authors: Li Yan , Yang Xia , Tao Lili , Zeng Weimei , Zuo Min , Li Shuo , Wu Liyan , Lin Yanshong , Zhang Ziying , Yun Jingping , Huang Yuhua 
Published: December 2022

Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell (FDC) sarcoma (EBV+ IFDCS) is a rare entity, and its histopathological characteristics have not been fully described. Here, we investigated the wide morphologic spectrum and immunophenotype of this tumor with the aim to help avoid misdiagnosis. Thirteen cases of EBV+ IFDCS were retrospectively analyzed, combined with a review of 70 cases reported in the literature. The median age of patients was 49 (range, 29 to 67 y). Six patients were male and 7 were female. Most cases (92.3%, 12/13) occurred in the liver or spleen, and only 1 case affected an extra-hepatosplenic site (lung, 7.7%, 1/13). Tumors were assessed for a variety of histologic features and assigned to the following morphologic groups: classic type (53.8%, 7/13), lymphoma-like subtype (38.5%, 5/13), and hemangioma-like subtype (7.7%, 1/13). The classic type had distinct EBV-positive neoplastic cells with a fascicular or storiform growth pattern, variable lymphoplasmacytic infiltrates, and blood vessels. The lymphoma-like subtype had extremely prominent lymphoplasmacytic infiltrates (resembling marginal zone lymphoma with plasmacytoid differentiation) with singly dispersed distinct EBV-positive neoplastic cells, highlighted by in situ hybridization for EBV-encoded small RNA. The hemangioma-like subtype had extremely prominent blood vessels with hyaline and/or fibrinoid degeneration, singly dispersed distinct EBV-positive neoplastic cells, and limited lymphoplasmacytic infiltrates. Immunohistochemically, the neoplastic cells showed variable staining for FDC markers (CD21, CD35, CD23, and SSTR2) and the fibroblastic marker SMA, with the staining ranging from very focal to extensive. The number of EBV-positive neoplastic cells ranged from 80 to 400/HPF. All cases showed variable expression of PD-ligand 1 (PD-L1) (CPS: 5-90). IgG4-positive cells ranged from rare up to 100/HPF. Interestingly, 2 cases satisfied the criteria proposed in a previous study, mimicking IgG4-related disease. EBV+ IFDCS is an entity with an extremely wide morphologic spectrum and immunophenotype. Awareness of the spectrum of morphologic presentations of this rare tumor, specifically the lymphoma-like subtype and hemangioma-like subtype, is important for accurate diagnosis.
A Single-Center Study of Long-Term Effectiveness of Vedolizumab in Anti-TNF Refractory Pediatric Inflammatory Bowel Disease
Authors: Patel Halee , Karam Lina , Kellermayer Richard 
Published: December 2022

Objectives:
Vedolizumab is an anti-α4β7 integrin antibody that has been used successfully in the treatment of adult-onset inflammatory bowel diseases (IBDs: Crohn disease [CD] and ulcerative colitis [UC]). Its off-label use in the pediatric IBD (PIBD) population is increasing, but knowledge on durability beyond 6 months of treatment is limited.

Methods:
A real-life, single-center, retrospective study of PIBD patients treated with vedolizumab was performed. Data on demographics, prior and concomitant treatments, and disease activity were obtained at 14 weeks, 26 weeks, 1 year, and 2 years of therapy. Primary outcome was corticosteroid- and other biologic-free remission (based on pediatric ulcerative colitis activity index [PUCAI]).

Results:
Thirty-nine patients were studied. By 1 year, 65% of CD and 68% of UC patients continued on vedolizumab therapy. Corticosteroid- and other biologic-free remission was 29% in CD and 16% in UC. By 2 years, 36% of CD and 47% of UC patients continued therapy. Corticosteroid- and other biologic-free remission was 21% in CD and 40% in UC. By 2 years, 80% of CD and 100% of UC patients were on intensified treatment regimen compared to the manufacturer guidance. Nine patients (23%) required surgical intervention within 26 months of starting vedolizumab indicating the severity of IBD in this cohort.

Conclusions:
Vedolizumab is a useful therapeutic modality in PIBD patients refractory to anti-TNF therapy, although with declining effectiveness by 2 years. Intensified treatment regimens are associated with long-term durability. Larger prospective trials in children are warranted.
Puberty differentially predicts brain maturation in male and female youth: A longitudinal ABCD Study
Authors: Beck Dani , Ferschmann Lia , MacSweeney Niamh , Norbom Linn B. , Wiker Thea , Aksnes Eira , Karl Valerie , Dégeilh Fanny , Holm Madelene , Mills Kathryn L. , Andreassen Ole A. , Agartz Ingrid , Westlye Lars T. , Soest Tilmann von , Tamnes Christian K. 
Published: December 2022

AbstractResearch has demonstrated associations between pubertal development and brain maturation. However, existing studies have been limited by small samples, cross-sectional designs, and inconclusive findings regarding directionality of effects and sex differences.We examined the longitudinal temporal coupling of puberty status assessed using the Pubertal Development Scale (PDS) and magnetic resonance imaging (MRI)-based grey and white matter brain structure. Our sample consisted of 8,896 children and adolescents at baseline (mean age = 9.9) and 6,099 at follow-up (mean age = 11.9) from the Adolescent Brain and Cognitive Development (ABCD) Study.Applying multigroup Bivariate Latent Change Score (BLCS) models, we found that baseline PDS predicted the rate of change in cortical thickness among females and rate of change in cortical surface area for both males and females. We also found a correlation between baseline PDS and surface area and co-occurring changes over time in males. Diffusion tensor imaging (DTI) analysis revealed correlated change between PDS and fractional anisotropy (FA) for both males and females, but no significant associations for mean diffusivity (MD).Our results suggest that pubertal status predicts cortical maturation, and that the strength of the associations differ between sex. Further research is needed to understand the impact of environmental and lifestyle factors.
Comparison of multiple whole-genome andSpike-only sequencing protocols for estimating variant frequencies via wastewater-based epidemiology
Authors: Winder Lucy A. , Parsons Paul , Horsburgh Gavin , Maher Kathryn , Hipperson Helen , Wierzbicki Claudia , Jeffries Aaron R. , Brown Mathew R. , Fairbrother-Browne Aine , Denise Hubert , Khalifa Mohammad S. , Bassano Irene , van Aerle Ronny , Williams Rachel , Farcas Kata , Paterson Steve , Blackwell Paul G. , Burke Terry 
Published: December 2022

AbstractSequencing of SARS-CoV-2 in wastewater provides a key opportunity to monitor the prevalence of variants spatiotemporally, potentially facilitating their detection simultaneously with, or even prior to, observation through clinical testing. However, there are multiple sequencing methodologies available. This study aimed to evaluate the performance of alternative protocols for detecting SARS-CoV-2 variants. We tested the detection of two synthetic RNA SARS-CoV-2 genomes in a wide range of ratios and at two concentrations representative of those found in wastewater using whole-genome andSpike-gene-only protocols utilising Illumina and Oxford Nanopore platforms. We developed a Bayesian hierarchical model to determine the predicted frequencies of variants and the error surrounding our predictions. We found that most of the sequencing protocols detected polymorphic nucleotide frequencies at a level that would allow accurate determination of the variants present at higher concentrations. Most methodologies, including theSpike-only approach, could also predict variant frequencies with a degree of accuracy in low-concentration samples but, as expected, with higher error around the estimates. All methods were additionally confirmed to detect the same prevalent variants in a set of wastewater samples. Our results provide the first quantitative statistical comparison of a range of alternative methods that can be used successfully in the surveillance of SARS-CoV-2 variant frequencies from wastewater.ImpactGenetic sequencing of SARS-CoV-2 in wastewater provides an ideal system for monitoring variant frequencies in the general population. The advantages over clinical data are that it is more cost efficient and has the potential to identify new variants before clinical testing. However, to date, there has been no direct comparison to determine which sequencing methodologies perform best at identifying the presence and prevalence of variants. Our study compares seven sequencing methods to determine which performs best. We also develop a Bayesian statistical methodology to estimate the confidence around variant frequency estimates. Our results will help monitor SARS-CoV-2 variants in wastewater, and the methodology could be adapted for other disease monitoring, including future pandemics.
Emergence of new enhancers at late DNA replicating regions
Authors: Cornejo-Páramo Paola , Petrova Veronika , Zhang Xuan , Young Robert S. , Wong Emily S. 
Published: December 2022

AbstractEnhancers are fast-evolving genomic sequences that control spatiotemporal gene expression patterns. By examining enhancer turnover across mammalian species and in multiple tissue types, we uncovered a relationship between the emergence of novel enhancers and genome organization as a function of germline DNA replication time. While enhancers are most abundant in euchromatic regions, new enhancers emerged almost twice as often in late compared to early germline replicating regions, independent of transposable elements. Using a sequence model, we demonstrate that new enhancers are enriched for mutations that alter transcription factor (TF) binding. Recently evolved enhancers appeared to be mostly neutrally evolving and enriched in eQTLs. They also show more tissue specificity than conserved enhancers, and the TFs that bind to these elements, as inferred by binding sequences, also show increased tissue-specific gene expression. We find a similar relationship with DNA replication time in cancer, suggesting that these observations may be time-invariant principles of genome evolution. Our work underscores that genome organization has a profound impact in shaping mammalian gene regulation.
Fibroblasts-derived extracellular vesicles contain SFRP1 and mediate pulmonary fibrosis
Authors: Burgy Olivier , Mayr Christoph H. , Llobell Beatriz Ballester , Sengupta Arunima , Schenesse Déborah , Coughlan Christina , Parimon Tanyalak , Chen Peter , Lindner Michael , Hilgendorff Anne , Mann Matthias , Yildirim Ali Önder , Eickelberg Oliver , Schiller Herbert B. , Lehmann Mareike , Burgstaller Gerald , Königshoff Melanie 
Published: December 2022

AbstractIdiopathic pulmonary fibrosis (IPF) is a lethal and chronic lung disease characterized by aberrant intercellular communication, increased extracellular matrix (ECM) deposition, and destruction of functional lung tissue. Extracellular vesicles (EVs) accumulate within the lung in IPF, but their cargo and biological effects remain unclear. Here, we provide the entire the proteome of EV and non-EV fraction during pulmonary fibrosis, and functionally characterize their contribution to fibrosis. EVs were isolated by differential ultracentrifugation of bronchoalveolar lavage fluid (BALF) collected from mice challenged with bleomycin (or PBS as control) or culture supernatants from primary mouse lung fibroblasts. EVs were characterized by nanoparticle tracking analysis, Western Blotting, and quantitative mass spectrometry to define their proteome. EVs accumulation peaked at 14 days post-bleomycin instillation and correlated with decreased lung function. Label-free proteomics identified 107 proteins specific to fibrotic BALF-EVs. This signature was associated with wound healing, extracellular matrix organization, and cell motility. BALF-EVs from fibrotic lungs promoted fibrogenesis, including induction of ECM proteins in precision cut lung slicesex vivoand impaired alveolar epithelial cell stem cell function. Deconvolution using single cell RNA sequencing datasets revealed that fibroblasts are the major cellular source of BALF-EVs. EVs from fibroblasts were significantly enriched in Secreted Frizzled Related Protein 1 (SFRP1). In the lungs of patients with IPF, SFRP1 was significantly increased in mesenchymal cells.Sfrp1deficiency reduced the ability of fibroblast-derived EVs to potentiate bleomycin-induced lung fibrosisin vivoand led to a reduction in fibrosis marker gene expression. In sum, EVs carry specific protein cargos, such as SFRP1, to contribute to organ remodeling during fibrosis. Our data identified EVs transporting SFRP1 as a potential therapeutic target for IPF.
Optimized CRISPR guide RNA library cloning reduces skew and enables more compact genetic screens
Authors: Heo Seok-Jin , Enriquez Lauren D. , Federman Scot , Chang Amy Y. , Mace Rachel , Shevade Kaivalya , Nguyen Phuong , Litterman Adam J. , Shafer Shawn , Przybyla Laralynne , Chow Eric D. 
Published: December 2022

ABSTRACTThe development of CRISPR genetic screening tools has improved functional genomics, as these tools enable precise genomic editing, provide broad access to genomic regions beyond protein-coding genes, and have fewer off-target effects than other functional genomics modalities, allowing for novel applications with smaller library sizes compared to prior technologies. Pooled functional genomics screens require high cellular coverage per perturbation to accurately quantify phenotypes and average out phenotype-independent variability across the population. While more compact libraries have decreased the number of cells needed for a given screen, the cell coverage required for large-scale CRISPR screens still poses technical hurdles to screen in more challenging systems, such as iPSC-derived and primary cells. A major factor that influences cell coverage is screening library uniformity, as larger variation in individual guide RNA abundance requires higher cell coverage to reliably measure low-abundance guides. In this work, we have systematically optimized guide RNA cloning procedures to decrease bias. We implement these protocols to demonstrate that CRISPRi screens using 10-fold fewer cells than the current standard provides equivalent statistically significant hit-calling results to screens run at higher coverage, opening the possibility of conducting genome-wide and other large-scale CRISPR screens in technically challenging models.
The Cost of Adaptability: Resource Availability Constrains Functional Stability Under Pulsed Disturbances
Authors: Rain-Franco Angel , Peter Hannes , de Moraes Guilherme P. , Beier Sara 
Published: December 2022

AbstractGlobal change exposes ecosystems to changes in the frequency, magnitude and concomitancy of disturbances, which impact the composition and functioning. Here we experimentally evaluate effects of salinity disturbances and eutrophication on bacterial communities from coastal ecosystems. The resistance, resilience and functional stability of these communities is critically important for water quality, productivity and consequently ecosystem services, such as fishery yields. Yet, little is known about the underlying traits. Microbial functional stability can be maintained via resistance and resilience, which are reflected in genomic traits such as genome size and codon usage bias and may be linked to metabolic costs. To study the impact of pulsed disturbances on community assembly and functioning in dependence of metabolic costs, we performed a 41-days pulse disturbance experiment crossed with two levels of resource availability. Our setup triggered stochastic community re-assembly processes in all treatments. In contrast, we observed consistent and resource availability dependent patterns of superordinate community structural patterns and functioning, such as genomic trait distributions, species diversity, and functional resistance in response to disturbances. Genomic traits reflected the selection for taxa possessing resistant- and resilience-related traits, particularly under high nutrient availability. Our findings thereby mark an important step towards unraveling the compositional and genomic underpinnings of functional resistance in microbial communities after exposure to consecutive pulse disturbances. Our work demonstrates how resource availability alleviates metabolic constraints on resistance and resilience. This has important consequences for predicting water quality and ecosystem productivity of environments exposed to global change.SignificanceUnderstanding the responses of communities to disturbances is a prerequisite to predict ecosystem dynamics and thus highly relevant in light of global change. Microbial communities play key roles in numerous ecosystem functions and services, and the large diversity, rapid growth and phenotypic plasticity of microorganisms are thought to allow for high resistance and resilience. While potential metabolic costs associated with adaptions to fluctuating environments have been debated, little evidence supports trade-offs between resource availability and resistance and resilience. Here, we experimentally assessed the compositional and functional responses of an aquatic microbial model community to disturbances and systematically manipulated resource availability. Our results demonstrate that the capacity to tolerate environmental fluctuations is encoded in genomic traits and constrained by resource availability.
LegNet: a best-in-class deep learning model for short DNA regulatory regions
Authors: Penzar Dmitry , Nogina Daria , Noskova Elizaveta , Zinkevich Arsenii , Meshcheryakov Georgy , Lando Andrey , Rafi Abdul Muntakim , de Boer Carl , Kulakovskiy Ivan V. 
Published: December 2022

AbstractMotivationThe increasing volume of data from high-throughput experiments including parallel reporter assays facilitates the development of complex deep learning approaches for DNA regulatory grammar.ResultsHere we introduce LegNet, an EfficientNetV2-inspired convolutional network for modeling short gene regulatory regions. By approaching the sequence-to-expression regression problem as a soft classification task, LegNet secured first place for theautosome.orgteam in the DREAM 2022 challenge of predicting gene expression from gigantic parallel reporter assays. Using published data, here we demonstrate that LegNet outperforms existing models and accurately predicts gene expressionper seas well as the effects of single-nucleotide variants. Furthermore, we show how LegNet can be used in a diffusion network manner for the rational design of promoter sequences yielding the desired expression level.Availability and Implementationhttps://github.com/autosome-ru/LegNet. The GitHub repository includes the Python code under the MIT license to reproduce the results presented in the study and a Jupyter Notebook tutorial.Supplementary InformationOnline-only supplementary data are available at Bioinformatics online.Contactdmitrypenzar1996@gmail.com,ivan.kulakovskiy@gmail.com
WUREN: Whole-modal fUsion Representation for protein interaction interfacE predictioN
Authors: Wang Xiaodong , Gao Xiangrui , Fan Xuezhe , Huai Zhe , Yao Mengcheng , Wang Tianyuan , Huang Xiaolu , Lai Lipeng 
Published: December 2022

ABSTRACTProteins are one of the most important components in life, and the research on protein complex and the development of protein or antibody drugs relies on effective representation of proteins. Both experimental methods like cryo-electron microscopy and computational methods like molecular dynamic simulation suffer from high cost, long time investment and low throughput, and cannot be used in large-scale studies. Some examples of artificial intelligence for protein complex prediction tasks show that different representations of proteins have their own limitations. This paper constructs a multimodal model named WUREN (Whole-modal fUsion Representation for protein interaction interfacE predictioN), which effectively fuses sequence, graph, and structural features. WUREN has achieved state-of-the-art performance on both the antigen epitope prediction task and the protein-protein interaction interface prediction task, with AUC-PR reaching 0.462 and 0.516, respectively. Our results show that WUREN is a general and effective feature extraction model for protein complex, which can be used in the development of protein-based drugs. Furthermore, the general framework in WUREN can be potentially applied to model similar biologics to proteins, such as DNA and RNA.
Biodiversity and Conservation Priority Setting for the Vascular Flora of New Guinea
Authors: Smith Michael Gerard , Forest Felix , Rosindell James 
Published: December 2022

AbstractAimsNew Guinea is one of the world’s most floristically diverse islands, but its plant collection records are very uneven. We aim to identify which areas have the highest diversity of vascular plant genera, and which areas have the highest deforestation risk. Combining these findings we highlight priority regions for research and conservation.LocationNew GuineaTime period1900–2021Taxa studiedTracheophyta (Vascular plants)MethodsWe obtained collection records and environmental variables and prepared a cost-distance map of New Guinea to indicate accessibility. We modelled the joint distribution of 1,156 genera with the ‘Hmsc’ package in R to predict biodiversity across space, accounting for collection bias. We combined these results with a genus-level phylogenetic tree to predict phylogenetic endemism. We then modelled deforestation risk with the ‘R-INLA’ package, using forest clearance data and variables including cost-distance. We compared actual and predicted deforestation, and made predictions for 2021–25. Finally, we developed a combined measure of predicted biodiversity plus deforestation risk.ResultsA mean Spearman’s rank correlation of 0.462 was obtained on five-fold cross-validation of the genus biodiversity model; bias-correction shifted the predicted distribution of biodiversity towards western New Guinea, but had less effect on estimates of phylogenetic endemism.Predictions of relative deforestation probability were accurate over 5 and 10 years (Spearman values 0.66 and 0.71). We postulate a ‘deforestation debt’ to explain the persistence in accuracy. Over time, the areas which survive early deforestation gradually become more rewarding targets and the proportion of at-risk forest lost to clearance accumulates.Main conclusionsWe present a method for rapid assessment of biodiversity and deforestation risk in data-deficient tropical forest regions. Areas of high predicted biodiversity such as the Merauke and Jayapura lowlands are at high near-term risk from commercial deforestation, requiring urgent interventions to record and preserve threatened species.