tbuckley/cabot-search huggingface dataset:
Long-Term Exposures to Air Pollution and the Risk of Atrial Fibrillation in the Women’s Health Initiative Cohort
Authors: Jaime E. Hart, Chancellor Hohensee, Francine Laden, Isabel Holland, Eric A. Whitsel, Gregory A. Wellenius, Wolfgang C. Winkelmayer, Gloria E. Sarto, Lisa Warsinger Martin, JoAnn E. Manson, Philip Greenland, Joel Kaufman, Christine Albert, Marco V. Perez
Journal: Environmental Health Perspectives (2021)

Atrial fibrillation (AF) is associated with substantial morbidity and mortality. Short-term exposures to air pollution have been associated with AF triggering; less is known regarding associations between long-term air pollution exposures and AF incidence.Our objective was to assess the association between long-term exposures to air pollution and distance to road on incidence of AF in a cohort of U.S. women.We assessed the association of high resolution spatiotemporal model predictions of long-term exposures to particulate matter (PM10 and PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), and distance to major roads with incidence of AF diagnosis, identified through Medicare linkage, among 83,117 women in the prospective Women's Health Initiative cohort, followed from enrollment in Medicare through December 2012, incidence of AF, or death. Using time-varying Cox proportional hazards models adjusted for age, race/ethnicity, study component, body mass index, physical activity, menopausal hormone therapy, smoking, diet quality, alcohol consumption, educational attainment, and neighborhood socioeconomic status, we estimated the relative risk of incident AF in association with each pollutant.A total of 16,348 incident AF cases were observed over 660,236 person-years of follow-up. Most exposure-response associations were nonlinear. NO2 was associated with risk of AF in multivariable adjusted models [Hazard Ratio (HR)=1.18; 95% confidence interval (CI): 1.13, 1.24, comparing the top to bottom quartile, p-for-trend=<0.0001]. Women living closer to roadways were at higher risk of AF (e.g., HR=1.07; 95% CI: 1.01, 1.13 for living within 50m of A3 roads, compared with ≥1,000 m, p-for-trend=0.02), but we did not observe adverse associations with exposures to PM10, PM2.5, or SO2. There were adverse associations with PM10 (top quartile HR=1.10; 95% CI: 1.05, 1.16, p-for-trend=<0.0001) and PM2.5 (top quartile HR=1.09; 95% CI: 1.03, 1.14, p-for-trend=0.002) in sensitivity models adjusting for census region.In this study of postmenopausal women, NO2 and distance to road were consistently associated with higher risk of AF. https://doi.org/10.1289/EHP7683.
P14.82 Glioneuronal tumors - a rare tumor entity with diagnostic and therapeutic challenges: report of two cases and review of literature
Authors: A M Zeitlberger, M C Neidert, N Velez-Char, T Hundsberger
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The 2007 WHO classification of brain tumors first encompassed two new entities of glioneuronal tumors, including papillary glioneuronal tumors (PGNT) and rosette-forming glioneuronal tumours. The reviewed version of the 2016 WHO classification additionally included diffuse leptomeningeal glioneuronal tumours. The histopathological, genetic, and clinical understanding of glioneuronal tumors is currently evolving, however there are no guidelines for diagnostic and clinical management yet. MATERIAL AND METHODS We report two male patients with glioneuronal tumors and performed a review of literature. RESULTS The first patient was diagnosed with a PGNT (MIB-1 proliferation index = 5%) located in the right parietal lobe at the age of 33 years and received surgical resection. Two years later, the tumor recurred in the same location. A second tumor resection was performed followed by concomitant radiochemotherapy with temozolomide (60/2 Gray). A next-generation sequencing gene panel (Oncomine) confirmed the initial diagnosis of a PGNT. The patient has remained in remission for the past 10 years. The second patient developed complex partial seizures which were first misdiagnosed as anxiety disorder at the age of 26 years. An MRI scan revealed a contrast-enhancing bifrontal cystic lesions 5 years later and he received a gross total tumor resection. The diagnosis of a glioneuronal tumor was made, however molecular pathology and methylation analysis were not able to classify the tumor entity further. There was no evidence of tumor recurrence one year after surgery and he remained seizure-free with antiepileptic treatment. CONCLUSION Glioneuronal tumors encompass rare and heterogenous tumor entities which primarily present in young patients and often show a favorable clinical course. Although the increasing number of reports in the literature have improved our understanding of these tumors, uncertainty remains in diagnostic challenging cases and patients with progressive disease after surgery. The value of next-generation sequencing and the choice of adjuvant treatment modalities have not been systematically evaluated in this patient group.
SmProt: A Reliable Repository with Comprehensive Annotation of Small Proteins Identified from Ribosome Profiling
Authors: Yanyan Li, Honghong Zhou, Xiaomin Chen, Yu Zheng, Quan Kang, Di Hao, Lili Zhang, Tingrui Song, Huaxia Luo, Yajing Hao, Runsheng Chen, Peng Zhang, Shunmin He
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Small proteins specifically refer to proteins consisting of less than 100 amino acids translated from small open reading frames (sORFs), which were usually missed in previous genome annotation. The significance of small proteins has been revealed in current years, along with the discovery of their diverse functions. However, systematic annotation of small proteins is still insufficient. SmProt was specially developed to provide valuable information on small proteins for scientific community. Here we present the update of SmProt, which emphasizes reliability of translated sORFs, genetic variants in translated sORFs, disease-specific sORF translation events or sequences, and remarkably increased data volume. More components such as non-ATG translation initiation, function, and new sources are also included. SmProt incorporated 638,958 unique small proteins curated from 3,165,229 primary records, which were computationally predicted from 419 ribosome profiling (Ribo-seq) datasets or collected from literature and other sources from 370 cell lines or tissues in 8 species (Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Danio rerio, Saccharomyces cerevisiae, Caenorhabditis elegans, and Escherichia coli). In addition, small protein families identified from human microbiomes were also collected. All datasets in SmProt are free to access, and available for browse, search, and bulk downloads at http://bigdata.ibp.ac.cn/SmProt/.
KS01.6.A Comparative analysis of the immune compartment in human glioblastoma and IDH-mutant WHO grade 4 astrocytoma reveals profound differences in microglia phenotypes
Authors: R Sankowski, M Friedrich, L Bunse, H H Heiland, M Platten, M Prinz
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastoma (GBM) are the most common primary brain tumors. If untreated the average survival is around 12–18 months. Unfortunately, despite extensive research efforts, the therapeutic options remain limited. One major aspect complicating therapeutic development is an immunosuppressive tumor microenvironment. Isocitrate dehydrogenase (IDH)-mutant, WHO grade 4 astrocytomas appear histologically indistinguishable from GBM, but show significantly longer survival times. IDH mutations lead to changes in the tumor microenvironment with accrual of the neometabolite R-2-hydroxyglutarate. Previous studies on bulk transcriptomes have shown differences in the immune compartment of both tumor entities that were linked to the differences in clinical behavior. MATERIAL AND METHODS We have conducted high-dimensional comparative analyses of the myeloid compartment in surgically resected human GBM and IDH-mutant WHO grade 4 astrocytomas using single-cell RNA-Sequencing and immunohistochemistry. Histologically normal brain regions from epilepsy patients were used as controls. For analysis, whole-cell suspensions were prepared from freshly resected tumors or controls. Fluorescence activated cell sorting was used for myeloid cell enrichment. Samples were processed using the high-sensitivity single-cell RNA sequencing protocol CEL-Seq2. Seurat and StemID2 algorithms were used for clustering, differential gene expression and pseudotime analysis. Protein validation was achieved using immunohistochemistry. RESULTS We identified profound transcriptional changes of glioma-associated microglia in GBM with respect to control brain samples. Namely, we observed a global upregulation of major histocompatibility complex associated genes in GBM across all clusters. Additionally, we identified distinct myeloid subsets with phagocytic, hypoxia-associated and chemotactic transcriptomic signatures. Pseudotime analysis finely resolved transitional cell states. These changes were dramatically attenuated in IDH-mutant WHO grade 4 astrocytomas. The myeloid cells in these tumors resembled homeostatic microglia and showed an increased expression of cytokine and chemokine genes. CONCLUSION Here, we present a high-dimensional transcriptomic atlas of the myeloid compartment in human GBM and IDH-mutant WHO grade 4 astrocytomas. The identified differences point towards targeted therapeutic options via the modulation of the tumor microenvironment.
TGF-β promotes microtube formation in glioblastoma through thrombospondin 1
Authors: Justin V Joseph, Capucine R Magaut, Simon Storevik, Luiz H Geraldo, Thomas Mathivet, Md Abdul Latif, Justine Rudewicz, Joris Guyon, Matteo Gambaretti, Frida Haukas, Amalie Trones, Lars A Rømo Ystaas, Jubayer A Hossain, Sandra Ninzima, Sylvain Cuvellier, Wenjing Zhou, Tushar Tomar, Barbara Klink, Lalit Rane, Bronwyn K Irving, Joanne Marrison, Peter O’Toole, Heiko Wurdak, Jian Wang, Zhang Di, Even Birkeland, Frode S Berven, Frank Winkler, Frank A E Kruyt, Andreas Bikfalvi, Rolf Bjerkvig, Thomas Daubon, Hrvoje Miletic
Journal: Neuro-Oncology (2021)

Abstract Background Microtubes (MTs), cytoplasmic extensions of glioma cells, are important cell communication structures promoting invasion and treatment resistance through network formation. MTs are abundant in chemoresistant gliomas, in particular, glioblastomas (GBMs), while they are uncommon in chemosensitive IDH-mutant and 1p/19q co-deleted oligodendrogliomas. The aim of this study was to identify potential signaling pathways involved in MT formation. Methods Bioinformatics analysis of TCGA was performed to analyze differences between GBM and oligodendroglioma. Patient-derived GBM stem cell lines were used to investigate MT formation under transforming growth factor-beta (TGF-β) stimulation and inhibition in vitro and in vivo in an orthotopic xenograft model. RNA sequencing and proteomics were performed to detect commonalities and differences between GBM cell lines stimulated with TGF-β. Results Analysis of TCGA data showed that the TGF-β pathway is highly activated in GBMs compared to oligodendroglial tumors. We demonstrated that TGF-β1 stimulation of GBM cell lines promotes enhanced MT formation and communication via calcium signaling. Inhibition of the TGF-β pathway significantly reduced MT formation and its associated invasion in vitro and in vivo. Downstream of TGF-β, we identified thrombospondin 1 (TSP1) as a potential mediator of MT formation in GBM through SMAD activation. TSP1 was upregulated upon TGF-β stimulation and enhanced MT formation, which was inhibited by TSP1 shRNAs in vitro and in vivo. Conclusion TGF-β and its downstream mediator TSP1 are important mediators of the MT network in GBM and blocking this pathway could potentially help to break the complex MT-driven invasion/resistance network.
Spotlight influenza: Influenza surveillance before and after the introduction of point-of-care testing in Denmark, season 2014/15 to 2018/19
Authors: Guido Benedetti, Tyra Grove Krause, Uffe Vest Schneider, Jan Gorm Lisby, Marianne Voldstedlund, Didi Bang, Ramona Trebbien, Hanne-Dorthe Emborg
Journal: Eurosurveillance (2021)

BackgroundIn Denmark, influenza surveillance is ensured by data capturing from existing population-based registers. Since 2017, point-of-care (POC) testing has been implemented outside the regional clinical microbiology departments (CMD).AimWe aimed to assess influenza laboratory results in view of the introduction of POC testing.MethodsWe retrospectively observed routine surveillance data on national influenza tests before and after the introduction of POC testing as available in the Danish Microbiological Database. Also, we conducted a questionnaire study among Danish CMD about influenza diagnostics.ResultsBetween the seasons 2014/15 and 2018/19, 199,744 influenza tests were performed in Denmark of which 44,161 were positive (22%). After the introduction of POC testing, the overall percentage of positive influenza tests per season did not decrease. The seasonal influenza test incidence was higher in all observed age groups. The number of operating testing platforms placed outside a CMD and with an instrument analytical time ≤ 3 h increased after 2017. Regionally, the number of tests registered as POC in the Danish Microbiological Database and the number of tests performed with an instrument analytical time ≤ 3 h or outside a CMD partially differed. Where comparable (71% of tests), the relative proportion of POC tests out of all tests increased from season 2017/18 to 2018/19. In both seasons, the percentage of positive POC tests resulted slightly lower than for non-POC tests.ConclusionPOC testing integrated seamlessly into national influenza surveillance. We propose the use of POC results in the routine surveillance of seasonal influenza.
A Functional BCI Model by the P2731 Working Group: Transducer
Authors: Guillermo Sahonero-Alvarez, Avinash Kumar Singh, Kamran Sayrafian, Luigi Bianchi, Avid Roman-Gonzalez
Journal: Brain-Computer Interfaces (2021)

A Brain-Computer Interface (BCI) can be considered as a technology that allows for alternative means of communication between humans and their environment using thoughts and intentions. The structure of this interface is composed of various stages, beginning with the acquisition of the brain signals, followed by several processing stages, and leading to the generation of feedback signals. The development of a BCI system involves a diverse set of expertise in order to produce a unique environment for continuous innovations. However, such diversity in technical background and expertise may lead to confusion in the terminology used by the community. As such, the IEEE P2731 WG has been tasked with the development of a functional model to facilitate the understanding of a BCI system. In this paper, we focus on the description of the functional elements that belong to the transducer stage of a BCI.
Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases
Authors: Pere Ginès, Laurent Castera, Frank Lammert, Isabel Graupera, Miquel Serra‐Burriel, Alina M. Allen, Vincent Wai‐Sun Wong, Phillipp Hartmann, Maja Thiele, Llorenç Caballeria, Robert J. de Knegt, Ivica Grgurevic, Salvador Augustin, Emmanuel A. Tsochatzis, Jörn M. Schattenberg, Indra Neil Guha, Andrea Martini, Rosa M. Morillas, Montserrat Garcia‐Retortillo, Harry J. de Koning, Núria Fabrellas, Judit Pich, Ann T. Ma, M. Alba Diaz, Dominique Roulot, Philip N. Newsome, Michael Manns, Patrick S. Kamath, Aleksander Krag
Journal: Hepatology (2021)

Abstract Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non‐alcoholic fatty liver disease and alcohol‐related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at‐risk populations. Thus far, a limited number of population‐based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate −18% to 27%‐in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression.
Diet-induced alteration of intestinal stem cell function underlies obesity and prediabetes in mice
Authors: Alexandra Aliluev, Sophie Tritschler, Michael Sterr, Lena Oppenländer, Julia Hinterdobler, Tobias Greisle, Martin Irmler, Johannes Beckers, Na Sun, Axel Walch, Kerstin Stemmer, Alida Kindt, Jan Krumsiek, Matthias H. Tschöp, Malte D. Luecken, Fabian J. Theis, Heiko Lickert, Anika Böttcher
Journal: Nature Metabolism (2021)

Abstract Excess nutrient uptake and altered hormone secretion in the gut contribute to a systemic energy imbalance, which causes obesity and an increased risk of type 2 diabetes and colorectal cancer. This functional maladaptation is thought to emerge at the level of the intestinal stem cells (ISCs). However, it is not clear how an obesogenic diet affects ISC identity and fate. Here we show that an obesogenic diet induces ISC and progenitor hyperproliferation, enhances ISC differentiation and cell turnover and changes the regional identities of ISCs and enterocytes in mice. Single-cell resolution of the enteroendocrine lineage reveals an increase in progenitors and peptidergic enteroendocrine cell types and a decrease in serotonergic enteroendocrine cell types. Mechanistically, we link increased fatty acid synthesis, Ppar signaling and the Insr–Igf1r–Akt pathway to mucosal changes. This study describes molecular mechanisms of diet-induced intestinal maladaptation that promote obesity and therefore underlie the pathogenesis of the metabolic syndrome and associated complications.
Frailty is associated with increased risk of cirrhosis disease progression and death
Authors: Sarah Wang, Reid Whitlock, Chelsea Xu, Sunil Taneja, Surender Singh, Juan G. Abraldes, Kelly W. Burak, Robert J. Bailey, Jennifer C. Lai, Puneeta Tandon
Journal: Hepatology (2021)

The Liver Frailty Index (LFI) is a well-studied tool that evaluates frailty in patients with cirrhosis. Consisting of grip strength, chair stands, and balance testing, the LFI has been associated with increased mortality in patients awaiting liver transplant. We aimed to extend our understanding of frailty in cirrhosis by exploring the relationship between the LFI and the risk of (1) cirrhosis progression, (2) mortality, and (3) unplanned hospitalizations, in both compensated and decompensated disease.Adult patients with cirrhosis from four centers in North America and one in India were included. Frailty was measured at baseline using the LFI and categorized as robust (LFI < 3.2), prefrail (LFI 3.2-4.5), and frail (LFI > 4.5). Progression of cirrhosis was defined by an increase in clinical stage, ranging from 1 to 5, from baseline using the D'Amico classification. Factors associated with progression, mortality, and hospitalizations were evaluated using multivariate regression models, with transplant as a competing risk. In total, 822 patients with cirrhosis were included. Average Model for End-Stage Liver Disease (MELD) score was 15.5 ± 6.0. In patients with compensated cirrhosis, being frail versus robust was associated with increased risk of progression to the next cirrhosis stage or to death (HR, 2.45; 95% CI, 1.14-5.29) and with an increased risk of unplanned hospitalizations (2.32; 95% CI, 1.13-4.79), after adjusting for age, sex, and MELD score. Similar HRs were observed in patients with decompensated cirrhosis.Frailty was an independent predictor of cirrhosis progression or death and unplanned hospitalization across patients with compensated and decompensated cirrhosis. Future studies are needed to evaluate the possibility of slowing cirrhosis disease progression by reversing or preventing frailty.
P16.03 Cerebral gliom alters the peripheral CD4+ T helper cell phenotype
Authors: M Mohme, C Maire, A Rünger, L Glau, E Tolosa, M Westphal, K Lamszus
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Cancer is a systemic disease. Due to the exceedingly rare occurrence of metastasis of cerebral glioma, systemic alterations have, however, not been considered to play a major role in disease progression of glioma. CD4+ T helper (TH) cells orchestrate the adaptive immune response in an antigen-specific, cytokine mediated manner. The aim of our study was to investigate how far cerebral glioma impacts the systemic CD4+ immune repertoire. MATERIAL AND METHODS We performed flow-cytometry analysis of the peripheral blood CD4+ TH cell phenotype and cytokine production in 100 patients with IDHwt, 30 IDHmut and 16 IDHmut 1p19q co-deleted gliomas in comparison with age-matched healthy donors (HD). Data was analyzed using a Fortessa LSR and Diva software. Multiparameter analyses were performed using UMAP and SpadeVizR trees. The study was approved by the ethics committee (PV4904). RESULTS We found a significant skewing of the peripheral immunophenotype in IDHwt glioma patients, showing a TH1 expansion and reduced numbers of T follicular helper cells (TFH), TH1* and mucosa associated invariant T (MAIT) cells (p&amp;lt;0.001), while TH2 and TH17 percentages remained stable compared to IDHmut and HD. Although TH1 cells were dominant in IDHwt patients (p&amp;lt;0.01), intracellular cytokine staining showed a reduction of IFNγ and TNFα production after in vitro stimulation, while IL-4 was significantly increased compared to HD (p&amp;lt;0.05). No alterations between all groups were observed in IL-2, IL-10 or IL-17 production. Profiling of metabolic surface markers further revealed increased expression of GLUT1 on CD4+ T cells in IDHwt patients, indicating an activated CD4+ repertoire compared to HD. CONCLUSION Taken together, our results show a CD4+ TH cell type specific skewing of the peripheral immune repertoire in patients with IDHwt gliomas. Our data highlights the importance of considering malignant glioma as a disease with profound systemic effects fundamentally altering the immune repertoire in affected patients.