bluuebunny/crossref_metadata_2025_split huggingface dataset:
A paradoxical population structure ofvarDBLα types in Africa
Authors: Tan Mun Hua , Tiedje Kathryn E. , Feng Qian , Zhan Qi , Pascual Mercedes , Shim Heejung , Chan Yao-ban , Day Karen P. 
Published: November 2023

ABSTRACTThevarmultigene family encodes theP. falciparumerythrocyte membrane protein 1 (PfEMP1), which is important in host-parasite interaction as a virulence factor and major surface antigen of the blood stages of the parasite, responsible for maintaining chronic infection. Whilst important in the biology ofP. falciparum, these genes (50 to 60 genes per parasite genome) are routinely excluded from whole genome analyses due to their hyper-diversity, achieved primarily through recombination. The PfEMP1 head structure almost always consists of a DBLα-CIDR tandem. Categorised into different groups (upsA, upsB, upsC), different head structures have been associated with different ligand-binding affinities and disease severities. We study how conserved individual DBLα types are at the country, regional, and local scales in Sub-Saharan Africa. Using publicly-available sequence datasets and a novel ups classification algorithm,cUps, we performed anin silicoexploration of DBLα conservation through time and space in Africa. In all three ups groups, the population structure of DBLα types in Africa consists of variants occurring at rare, low, moderate, and high frequencies. Non-rare variants were found to be temporally stable in a local area in endemic Ghana. When inspected across different geographical scales, we report different levels of conservation; while some DBLα types were consistently found in high frequencies in multiple African countries, others were conserved only locally, signifying local preservation of specific types. Underlying this population pattern is the composition of DBLα types within each isolate DBLα repertoire, revealed to also consist of a mix of types found at rare, low, moderate, and high frequencies in the population. We further discuss the adaptive forces and balancing selection, including host genetic factors, potentially shaping the evolution and diversity of DBLα types in Africa.
Chemokine Receptor 2 Is A Theranostic Biomarker for Abdominal Aortic Aneurysms
Authors: Elizondo-Benedetto Santiago , Sastriques-Dunlop Sergio , Detering Lisa , Arif Batool , Heo Gyu Seong , Sultan Deborah , Luehmann Hannah , Zhang Xiaohui , Gao Xuefeng , Harrison Kitty , Thies Dakkota , McDonald Laura , Combadière Christophe , Lin Chieh-Yu , Kang Yeona , Zheng Jie , Ippolito Joseph , Laforest Richard , Gropler Robert J. , English Sean J. , Zayed Mohamed A. , Liu Yongjian 
Published: November 2023

AbstractAbdominal aortic aneurysm (AAA) is a degenerative vascular disease impacting aging populations with a high mortality upon rupture. There are no effective medical therapies to prevent AAA expansion and rupture. We previously demonstrated the role of the monocyte chemoattractant protein-1 (MCP-1) / C-C chemokine receptor type 2 (CCR2) axis in rodent AAA pathogenesis via positron emission tomography/computed tomography (PET/CT) using CCR2 targeted radiotracer64Cu-DOTA-ECL1i. We have since translated this radiotracer into patients with AAA. CCR2 PET showed intense radiotracer uptake along the AAA wall in patients while little signal was observed in healthy volunteers. AAA tissues collected from individuals scanned with64Cu-DOTA-ECL1i and underwent open-repair later demonstrated more abundant CCR2+ cells compared to non-diseased aortas. We then used a CCR2 inhibitor (CCR2i) as targeted therapy in our established male and female rat AAA rupture models. We observed that CCR2i completely prevented AAA rupture in male rats and significantly decreased rupture rate in female AAA rats. PET/CT revealed substantial reduction of64Cu-DOTA-ECL1i uptake following CCR2i treatment in both rat models. Characterization of AAA tissues demonstrated decreased expression of CCR2+ cells and improved histopathological features. Taken together, our results indicate the potential of CCR2 as a theranostic biomarker for AAA management.Graphical Abstract
“Urban-Satellite” estimates in the ABCD Study: Linking Neuroimaging and Mental Health to Satellite Imagery Measurements of Macro Environmental Factors
Authors: Goldblatt Ran , Holz Nathalie , Tate Garrett , Sherman Kari , Ghebremicael Selamawit , Bhuyan Soumitra S , Al-Ajlouni Yazan , Santillanes Sara , Araya Ghermay , Abad Shermaine , Herting Megan M. , Thompson Wesley , Thapaliya Bishal , Sapkota Ram , Xu Jiayuan , Liu Jingyu ,   the environMENTAL consortium, Schumann Gunter , Calhoun Vince D. 
Published: November 2023

AbstractWhile numerous studies over the last decade have highlighted the important influence of environmental factors on mental health, globally applicable data on physical surroundings are still limited. Access to such data and the possibility to link them to epidemiological studies is critical to unlocking the relationship of environment, brain and behaviour and promoting positive future mental health outcomes. The Adolescent Brain Cognitive Development (ABCD) Study is the largest ongoing longitudinal and observational study exploring brain development and child health among children from 21 sites across the United States. Here we describe the linking of the ABCD study data with satellite-based “Urban-Satellite” (UrbanSat) variables consisting of 11 satellite-data derived environmental indicators associated with each subject’s residential address at their baseline visit, including land cover and land use, nighttime lights, and population characteristics. We present these UrbanSat variables and provide a review of the current literature that links environmental indicators with mental health, as well as key aspects that must be considered when using satellite data for mental health research. We also highlight and discuss significant links of the satellite data variables to the default mode network clustering coefficient and cognition. This comprehensive dataset provides the foundation for large-scale environmental epidemiology research.
KUL@SMM4H’23: Text Augmentations with R-drop for Classification of Tweets Self Reporting Covid-19
Authors: Francis Sumam , Moens Marie-Francine 
Published: November 2023

AbstractThis paper presents models created for the Social Media Mining for Health 2023 shared task. Our team addressed the first task, classifying tweets that self-report Covid-19 diagnosis. Our approach involves a classification model that incorporates diverse textual augmentations and utilizes R-drop to augment data and mitigate overfitting, boosting model efficacy. Our leading model, enhanced with R-drop and augmentations like synonym substitution, reserved words, and back translations, outperforms the task mean and median scores. Our system achieves an impressive F1 score of 0.877 on the test set.
Early inflammatory response mediated by Angiotensin II in cardiac arteries of normotensive mice
Authors: Oliveira Thais Cristina de Souza , Viegas Katia Aparecida da Silva , Lima Rariane Silva de , Alba-Loureiro Tatiana C. , Lima Cintia Taniguti , Campos Luciene Cristina Gastalho , Barauna Valerio Garrone , Curi Rui , Irigoyen Maria Claudia , Lacchini Silvia 
Published: November 2023

ABSTRACTTo verify if a low dose of angiotensin II (Ang II) can induce an inflammatory response in cardiac arteries, even though blood pressure remains at normal values. Were used C57Bl/6J male mice treated with a low dose of Ang II (30ng/kg IP) and AT1R blockers. Blood pressure was recorded after 10, 30, 60min, 2 and 6hours after Saline or Ang II injection. Time curve (30 and 60min, 2, 6, 12, 24, and 48hours after treatment) for expression of inflammatory markers was evaluated in cardiac arteries (TGF-β, IL-1β, IL-6, TNF-α and ICAM-1) by immunohistochemistry and western blot. Serum TNF-α and IL-6 were analyzed by ELISA. Although Ang II did not alter blood pressure, local TGF-α and IL-6 presented an early increase in cardiac arteries. IL-1β and ICAM-1 participated in a late response to Ang II (12 hours). Ang II group showed a systemic increase of IL-6 30 to 60 minutes after treatment. AT1 and AT2 receptor blockers (losartan, 20mg/kg, and PD123.319, 15mg/kg) were given alone or concomitant to Ang II. This combination showed that Ang II increases TGF-β and IL-6 by acting on the AT1 receptor in a fast response. IL-1β regulation by Ang II seems to be mediated by both AT1 and AT2 receptors. The results suggest that, independently of hemodynamic influences, Ang II, acting on AT1R, leads to the expression of inflammatory markers in cardiac vessels. AT2 receptor seems to be involved in the counterbalance of AT1R during modulation of IL-1β production in cardiac arteries.
BIOMAPP::CHIP: Large-Scale Motif Analysis
Authors: Caldonazzo Garbelini Jader M. , Sanches Danilo S. , Ramirez Pozo Aurora T. 
Published: November 2023

AbstractBackgroundDiscovery biological motifs plays a fundamental role in understanding regulatory mechanisms. Computationally, they can be efficiently represented askmers, making the counting of these elEMents a critical aspect for ensuring not only the accuracy but also the efficiency of the analytical process. This is particularly useful in scenarios involving large data volumes, such as those generated by theChIP-seqprotocol. Against this backdrop, we introducebiomapp ::chip, a tool specifically designed to optimize the discovery of biological motifs in large data volumes.ResultsWe conducted a comprehensive set of comparative tests with state-of-the-art algorithms. Our analyses revealed thatbiomapp ::chipoutperforms existing approaches in various metrics, excelling both in terms of performance and accuracy. The tests demonstrated a higher detection rate of significant motifs and also greater agility in the execution of the algorithm. Furthermore, thesmtcomponent played a vital role in the system’s efficiency, proving to be both agile and accurate inkmercounting, which in turn improved the overall efficacy of our tool.Conclusionbiomapp ::chiprepresent real advancements in the discovery of biological motifs, particularly in large data volume scenarios, offering a relevant alternative for the analysis ofChIP-seqdata and have the potential to boost future research in the field. This software can be found at the following address:https://github.com/jadermcg/BIOMAPP-CHIP.
Cutaneous T cell lymphoma atlas reveals malignant Th2 cells supported by a B cell-rich microenvironment
Authors: Li Ruoyan , Strobl Johanna , Poyner Elizabeth F.M. , Torabi Fereshteh , Mazin Pasha , Chipampe Nana-Jane , Stephenson Emily , Gardner Louis , Olabi Bayanne , Coulthard Rowen , Botting Rachel A. , Zila Nina , Prigmore Elena , Gopee Nusayhah , Engelbert Justin , Goh Issac , Chan Hon Man , Johnson Harriet , Ellis Jasmine , Rowe Victoria , Tun Win , Reynolds Gary , Foster April Rose , Gambardella Laure , Winheim Elena , Admane Chloe , Rumney Benjamin , Steele Lloyd , Jardine Laura , Nenonen Julia , Pickard Keir , Lumley Jennifer , Hampton Philip , Hu Simeng , Liu Fengjie , Liu Xiangjun , Horsfall David , Basurto-Lozada Daniela , Grimble Louise , Bacon Chris M. , Weatherhead Sophie , Brauner Hanna , Wang Yang , Bai Fan , Reynolds Nick J. , Allen Judith E. , Jonak Constanze , Brunner Patrick M. , Teichmann Sarah A. , Haniffa Muzlifah 
Published: November 2023

AbstractCutaneous T-cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides (MF), can be difficult to diagnose resulting in treatment delay. The pathogenesis of CTCL is not fully understood due to limited data from patient studies. We performed single-cell RNA sequencing and spatial transcriptomics profiling of skin from patients with MF-type CTCL, and an integrated comparative analysis with human skin cell atlas datasets from healthy skin, atopic dermatitis and psoriasis. We reveal the co-optation of Th2-immune gene programmes by malignant CTCL cells and modelling of the tumour microenvironment to support their survival. We identify MHC-II+fibroblast subsets reminiscent of lymph node T-zone reticular cells and monocyte-derived dendritic cells that can maintain Th2-like tumour cells. CTCL Th2-like tumour cells are spatially associated with B cells, forming aggregates reminiscent of tertiary lymphoid structures which are more prominent with progressive disease. Finally, we validated the enrichment of B cells in CTCL skin infiltrates and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL.
Nucleocapsid condensation drives Ebola viral factory maturation and dispersion
Authors: Vallbracht Melina , Bodmer Bianca S. , Fischer Konstantin , Makroczyova Jana , Winter Sophie L. , Wendt Lisa , Wachsmuth-Melm Moritz , Hoenen Thomas , Chlanda Petr 
Published: November 2023

SummaryReplication and genome encapsidation of many negative-sense RNA viruses take place in virus-induced membrane-less organelles termed viral factories (VFs). While liquid properties of VFs are believed to control the transition from genome replication to encapsidation, the nucleocapsid assembly, VF maturation and interactions with the cellular environment remain elusive. Here we applyin situcryo-correlative light and electron tomography to follow nucleocapsid assembly and changes in VF morphology and their liquid properties during Ebola virus infection. We show that Ebola viral nucleocapsids transition from loosely packed helical assemblies in early VFs to condensed cylinders that arrange into highly organized parallel bundles later in infection. Early VFs associate with intermediate filaments and are devoid of other host material, but become progressively accessible to cellular components. Our data suggest that this process is coupled to VF solidification and dispersion, and that changes in liquid properties of VFs promote nucleocapsid transport to budding sites.Highlights- Cryo-ET reveals the molecular architecture of Ebola virus replication compartments- Loosely coiled nucleocapsids transition to condensed cylinders forming bundles- Nucleocapsid condensation drives dispersion of viral factories promoting viral egress- Intermediate filaments associate with and are critical for virus factory formation
One infusion of engineered long-lasting and multifunctional T cells cures asthma in mice
Authors: Jin Gang , Liu Yanyan , He Zihao , Wang Lixia , Zhao Xiaocui , Li Zhuoyang , Yin Na , Peng Min 
Published: November 2023

SummaryThe majority of common chronic human diseases are incurable, which affect a large portion of population and require life-long treatments that impose huge disease, economic and social burden. For example, asthma is the most common respiratory disease affecting over 300 million people and accounts for > 250,000 death annually, for which there is no cure. Unlike traditional therapyies, engineered T cells, such as chimeric antigen receptor CAR T (CAR-T) cells, function as living drugs and can cure some hematological malignancies, but whether engineered T cells can cure common diseases beyond cancer remains elusive. Here, we develop a curative therapy for asthma based on enginerred T cell. With IL-5 as the targeting domain and depletion of BCOR and ZC3H12A, we produce long-lasting CAR-T cells eradicating IL-5Rα+eosinophils, termedImmortal-like andFunctional IL-5 CAR-T cells (5TIF) cells. We further enginerred 5TIFcells to secrete an IL-4 mutein that blocks the singaling of both IL-4 and IL-13, two driver inflammatory cytokines in asthma, named as 5TIF4 cells. In multiple models of asthma, one infusion of 5TIF4 cells in fully immunocompetent mice, in the absence of any conditioning regimen, confers long-term depletion of pathological eosinophils and blockade of IL-4/IL-13 actions, resulting in sustained repression of type 2 inflammation and asthmatic symptoms. Furthurmore, 5TIF4 cells can also be induced in human T cells in NSG mice. Our data demonstrate that asthma, a common noncancerous disease, can be cured by a single infusion of engineered long-lasting and multifunctional T cells, which paves the way for curing common chronic diseases by engineered long-lived T cells.
Differential quantification of alternative splicing events on spliced pangenome graphs
Authors: Ciccolella Simone , Cozzi Davide , Vedova Gianluca Della , Kuria Stephen Njuguna , Bonizzoni Paola , Denti Luca 
Published: November 2023

AbstractPangenomes are becoming a powerful framework to perform many bioinformatics analyses taking into account the genetic variability of a population, thus reducing the bias introduced by a single reference genome. With the wider diffusion of pangenomes, integrating genetic variability with transcriptome diversity is becoming a natural extension that demands specific methods for its exploration. In this work, we extend the notion of spliced pangenomes to that ofannotated spliced pangenomes; this allows us to introduce a formal definition of Alternative Splicing (AS) events on a graph structure.To investigate the usage of graph pangenomes for the quantification of AS events across conditions, we developedpantas, the first pangenomic method for the detection and differential analysis of AS events from short RNA-Seq reads. A comparison with state-of-the-art linear reference-based approaches proves thatpantasachieves competitive accuracy, making spliced pangenomes effective for conducting AS events quantification and opening future directions for the analysis of population-based transcriptomes.pantasis open-source and freely available atgithub.com/algolab/pantas.Author summaryThe ever increasing availability of complete genomes is advancing our comprehension of many biological mechanisms and is enhancing the knowledge we can extract from sequencing data. Pange3PM ESTnome graphs are a convenient way to represent multiple genomes and the genetic variability within a population. Integrating genetic variability with transcriptome diversity can improve our understanding of alternative splicing, a regulation mechanism which allows a single gene to code for multiple proteins. However, many unanswered questions are limiting our comprehension of the relationship between genetic and trancriptomic variations. With this work, we start to fill this gap by introducingpantas, the first approach based on pangenome graphs for the detection and differential quantification of alternative splicing events. A comparison with state-of-the-art approaches based on linear genome prove that pangenome graphs can be effectively used to perform such an analysis. By integrating genetic and transcriptome variability in a single structure,pantascan pave the way to next generation bioinformatic approaches for the accurate analysis of the relations between genetic variations and alternative splicing aberrations.
A single-cell multi-omic and spatial atlas of B-cell lymphomas reveals differentiation drives intratumor heterogeneity
Authors: Fitzgerald Donnacha , Roider Tobias , Baertsch Marc-Andrea , Kibler Artur , Horlova Anastasiia , Chung Erin , Vöhringer Harald , Mathioudaki Anna , Budeus Bettina , Passerini Verena , Knoll Mareike , Mammen Johannes , Li Linsha , Caillé Léandra , Czernilofsky Felix , Bruch Peter-Martin , Liebers Nora , Meyer-Bender Matthias , Siebert Reiner , Weigert Oliver , Zaugg Judith , Nolan Garry , Seifert Marc , Dietrich Sascha , Huber Wolfgang 
Published: November 2023

AbstractIntratumor heterogeneity underpins cancer pathogenesis and evolution, although it is typically considered independent from the differentiation processes that drive physiological cell-type diversity. As cancer types and subtypes arise from different cell types, we investigated whether cellular differentiation influences intratumor heterogeneity. Nodal B-cell non-Hodgkin lymphomas are a diverse set of cancers originating from different stages of B-cell maturation. Through single-cell transcriptome and surface epitope profiling (CITE-Seq) of diffuse large B-cell, mantle cell, follicular, and marginal zone lymphomas in addition to reactive lymph nodes from 51 patients, we found multiple B-cell maturation states within tumors. Intratumor maturation states emerged from the same clone, revealing divergent differentiation from a shared cell of origin. Maturation state composition varied across subtypes and tumors, which encompassed mixed cell-of-origin diagnostic subtypes. Through highly multiplexed immunohistochemistry (CODEX) of samples from 19 of these patients, we found that intratumor maturation states inhabited distinct spatial niches, displaying cellular interactions and regulatory networks typical of their maturation states while harboring different genetic variants. By deconvoluting intratumor maturation states from a microarray dataset of 507 patients, we identified risk groups within diagnoses with striking differences in survival, including IgM memory-enriched germinal center B-cell (M = 1.9 vs >10 years, p = 0.00039) and activated B-cell (M = 2.4 vs 9.6 years, p = 0.016) diffuse large B-cell lymphoma, and dark zone-enriched follicular lymphoma (M = 8.6 vs 13 years; p = 0.0019). Our findings reveal cellular differentiation remains plastic in B-cell lymphomas, driving tumor variation, evolution, and response.Key PointsCellular differentiation remains plastic in B-cell lymphomas, driving tumor variation, evolution, and response.Intratumor maturation states occupy unique immune niches, harbor distinct genetic variants, and are tied to different survival outcomes.
IC-VAE: A Novel Deep Learning Framework for Interpreting Multiplexed Tissue Imaging Data
Authors: Nguyen Huy , Vuong Hy , Truong Thao , Pham Son 
Published: November 2023

AbstractInterpreting protein expression in multiplexed tissue imaging data presents a significant challenge due to the high dimensionality of the resulting images, the variety of intracellular structures, cell shapes resulting from 2-D tissue sectioning, and the presence of technological noise and imaging artifacts. Here, we introduce the Information-Controlled Variational Autoencoder (IC-VAE), a deep generative model designed to tackle this challenge. The contribution of IC-VAE to the VAE framework is the ability to control the shared information among latent subspaces. We use IC-VAE to factorize each cell’s image into its true protein expression, various cellular components, and background noise, while controlling the shared information among some of these components. Compared with other normalization methods, this approach leads to superior results in downstream analysis, such as analyzing the expression of biomarkers, classification for cell types, or visualizing cell clusters using t-SNE/UMAP techniques.