bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring regional astrocyte diversity by cell-type specific proteomic labelingin vivo
Authors: Prabhakar Priyadharshini , Pielot Rainer , Landgraf Peter , Wissing Josef , Bayrhammer Anne , van Ham Marco , Gundelfinger Eckart D. , Jänsch Lothar , Dieterich Daniela C. , Müller Anke 
Published: June 2022

AbstractAstrocytes exhibit regional heterogeneity in morphology, function and molecular composition to support and modulate neuronal function and signaling in a region-specific manner. To characterize regional heterogeneity of astrocytic proteomes of different brain regions we established an Aldh1l1- MetRSL274Gmouse line that allows cell-type specific labeling of newly synthesized proteinsin vivoand analyzed astrocytic proteins from four different brain regions by mass spectrometry. Identified proteins are specific for astrocytes and show a high overlap with proteins compiled in ‘AstroProt’, a newly established database for astrocytic proteins. Gene enrichment analysis reveals high overlap among brain regions, and only subtle changes in abundances of key astrocytic proteins for hippocampus, cortex and striatum. However, the cerebellar proteome stands out with proteins being associated with calcium signaling or bipolar disorder. Subregional differences of translation dynamics in single hippocampal astrocytes indicates distinct subregional heterogeneity and highlights the applicability of our toolbox to study dynamic astrocytic proteomesin vivo.
Trans-Driver: a deep learning approach for cancer driver gene discovery with multi-omics data
Authors: Yang Hai , Zhang Lei , Zhou Dan , Li Dongdong , Zhang Jing , Wang Zhe 
Published: June 2022

AbstractDriver genes play a crucial role in the growth of cancer cells. Accurate identification of cancer driver genes is helping to strengthen the understanding of cancer pathogenesis and is conducive to the development of cancer treatment and drug-targe driver genes. However, due to the diversity and complexity of the multi-omics data, it is still challenging to identify cancer drivers.In this study, we propose Trans-Driver, a deep supervised learning method with a novel transformer network, which integrates multi-omics data to learn the differences and associations between different omics data for cancer drivers’ discovery. Compared with other state-of-the-art driver gene identification methods, Trans-Driver has achieved excellent performance on TCGA and CGC data Machine learning for multi-omics data integration in cancer. Among 20,000 protein-coding genes, Trans-Driver reported 185 candidate driver genes, of which 103 genes (about 55%) were included in the gold standard CGC data set. Finally, we analyzed the contribution of each feature to the identification of driver genes. We found that the integration of multi-omics data can improve the performance of our method compared with using only somatic mutation data. Through detailed analysis, we found that the candidate drivers are clinically meaningful, proving the practicability of Trans-Driver.Author summaryMany methods have been developed to identify cancer driver genes. However, most of these methods use single-omics data for cancer driver gene identification. Multi-omics-based methods for cancer driver gene identification are rare. Trans-Driver uses deep learning to process multi-omics data and learn the relationships between multi-omics data for cancer driver gene prediction. We have predicted 185 candidate cancer driver genes out of among 20,000 protein-coding genes. Also, we performed cancer driver gene prediction on 33 cancer types, and we identified the cancer driver genes corresponding to each cancer type. And, we observed that the predicted cancer driver genes were shown to have a role in cancer progression in recent studies. Our proposed method for cancer driver gene identification using multi-omics data has improved performance compared to using mutation data alone.
Redefining and subtyping of major depression based on brain functional connectivity signatures with high generalization: an ensemble hybrid framework
Authors: Zheng Kaizhong , Lu Hongbing , Wu Yuxia , Wang Huaning , Hu Dewen ,   the DIRECT consortium, Chen Badong , Li Baojuan 
Published: June 2022

AbstractCurrent clinical diagnosis of major depression is solely based on subjective symptoms and signs rather than the underlying biological mechanisms, which has hindered the improvement in treatment effectiveness and outcomes. Redefining and subtyping major depressive disorder (MDD) based on neural circuits has been an emerging consensus. Here, we proposed a novel ensemble hybrid deep-learning framework based on graph neural network for redefining and subtyping of MDD with the brain’s “fingerprinting”, i.e. nuanced functional connectivity profiles. A graph neural network (GNN) based supervised model was first employed to discriminate MDD patients from healthy controls. The graph embedding features obtained from the supervised classifier was then employed for subtyping of MDD with an unsupervised clustering by fast search and find of density peaks (CFDP) approach. The generalization accuracy and reproducibility of the proposed framework were further validated with one of the largest resting-state fMRI data set for MDD which included 2428 participants recruited from 25 independent sites. Our classifier showed a high generalization of 75% for leave-one-site-out cross validation. In addition, we obtained three biologically homogenous MDD subtypes characterized by impairments in subcortical-limbic, DMN-FPN, VN-SMN circuits, respectively. Notably, we demonstrated that subtyping of MDD according to graph embedding features showed high robustness and reproducibility across different sites. The proposed framework is not only essential for redefining and subtyping of MDD, but also paves the way towards precision medicine of mental disorders.
Root architecture plasticity in response to endoparasitic cyst nematodes is mediated by damage signaling
Authors: Guarneri Nina , Willig Jaap-Jan , Sterken Mark G. , Zhou Wenkun , Hasan M. Shamim , Grundler Florian M. W. , Willemsen Viola , Goverse Aska , Smant Geert , Lozano-Torres Jose L. 
Published: June 2022

SummaryPlant root architecture plasticity in response to biotic stresses has not been thoroughly investigated. Infection by the endoparasitic cyst nematodes induces root architectural changes that involve the formation of secondary roots at infection sites. However, the molecular mechanisms regulating secondary root formation in response to cyst nematode infection remain largely unknown.We first assessed whether secondary roots form in a nematode-density dependent manner by challenging wild type Arabidopsis plants with increasing numbers of cyst nematodes (Heterodera schachtii). Next, by using jasmonate-related reporter lines and knock-out mutants, we tested if tissue damage by nematodes triggers secondary root formation. Finally, we verified whether damage-induced secondary root formation depends on local auxin biosynthesis at nematode infection sites.Intracellular host invasion by H. schachtii triggers a transient local increase in jasmonates, which activates the expression of ERF109 in a COI1-dependent manner. Knock-out mutations in COI1 and ERF109 disrupt the nematode-density dependent increase of secondary roots observed in wildtype plants. Furthermore, ERF109 regulates secondary root formation upon H. schachtii infection via local auxin biosynthesis.Host invasion by H. schachtii triggers secondary root formation via the damage-induced jasmonate-dependent ERF109 pathway. This points at a novel mechanism underlying plant root plasticity in response to biotic stress.
Imagining and reading actions: towards similar motor representations
Authors: Dupont W , Papaxanthis C , Madden-Lombardi C , Lebon F 
Published: June 2022

AbstractWhile action language and motor imagery both engage the motor system, determining whether these two processes indeed share the same motor representations would contribute to better understanding their underlying mechanisms. We conducted two experiments probing the mutual influence of these two processes. In Exp.1, hand-action verbs were presented subliminally, and participants (n=36) selected the verb they thought they perceived from two alternatives. When congruent actions were imagined prior to this task, accuracy significantly increased, i.e. participants were better able to “see” the subliminal verbs. In Exp.2, participants (n=19) imagined hand flexion or extension, while corticospinal excitability was measured via transcranial magnetic stimulation. Corticospinal excitability was modulated by action verbs subliminally presented prior to imagery. Specifically, the typical increase observed during imagery was suppressed after presentation of incongruent action verbs. This mutual influence of action language and motor imagery, both at behavioral and neurophysiological levels, suggests overlapping motor representations.
A Tomato Genome From The Italian Renaissance Provides Insights Into Columbian and Pre-Columbian Exchange Links And Domestication
Authors: Vos Rutger , van Andel Tinde , Gravendeel Barbara , Kakakiou Vasia , Michels Ewout , Schijlen Elio , Stefanaki Anastasia 
Published: June 2022

AbstractThe history of the tomato’s interactions with humans spans both a pre-Columbian period of millennia of cultivation and domestication in South and Central America as well as the plant’s rise to becoming one of the world’s major cash crops following the arrival of Europeans in the Neotropics and the subsequent Columbian Exchange. In the process, the influence of successive regimes of artificial selection gave rise to an entangled species complex comprised of a wild ancestor and numerous cultivars exhibiting a great diversity of fruit phenotypes (often sorted in ‘cherry’ and big types). Here, we provide a snapshot into these dynamics by presenting the ancient nuclear and plastid genomes of one of the oldest tomatoes still in existence: the almost half a millennium old En Tibi specimen from the Italian Renaissance. By placing the genome skimming data obtained from this specimen within the phylogenomic context of wild relatives and Neotropical tomato cultivars and land races, we are able to show that the most likely geographic origins of the specimen’s immediate ancestors, i.e. whence the exchange of this particular lineage originated, are around the Gulf of Mexico. We also show that this specimen was less inbred than present-day tomatoes, shedding light on the genomic signatures of historical domestication processes. Probing deeper into the ancestry that shaped extant genetic diversity within the complex, we reconstruct multiple ancestral populations with diffuse but distinct signatures in cherry and big tomatoes. The geographic structure of these ancestries within the nearest wild relative of tomatoes and the differential extent to which these ancestries are represented in domesticates points to early cultivation and human-assisted dispersal of tomatoes originating from the northern extreme of the natural range of the species. Our findings illustrate the inferences that can be drawn from ancient DNA extracted from herbarium specimens and historic plant collections. At the same time, we stress that our findings draw on multiple disciplines including ethnobotanical and historical research and on the (agri)cultural contributions of a variety of world cultures.
HBs-S antigen-dependent enhancement of HBV infection
Authors: Sanada Takahiro , Yoshida Osamu , Hiasa Yoichi , Kohara Michinori 
Published: June 2022

AbstractBackground AimsIn natural infections with hepatitis B virus (HBV), large amounts of hepatitis B surface-small antigen (HBs-S) subviral particles (SVPs), which do not contain viral nucleocapsid, are secreted into the blood. The function of excess amounts of SVPs remains largely unknown. In this study, we analyzed the function of HBs-S in HBV infection.MethodsThe effect of HBs-S in HBV infection was evaluated in a human hepatoma cell line, in primary human hepatocytes, and in chimeric mice with humanized livers. To analyze the involvement of glycosaminoglycan, HBs-S attachment to cells in the presence of heparin was evaluated by enzyme-linked immunosorbent assay (ELISA), and the enhancement of viral attachment was evaluated by measurement of viral DNA. Additionally, the interaction between HBs-S and viral particles was analyzed by immunoprecipitation.ResultsAttachment of the HBV DNA to cells inoculated with the combination of virus and HBs-S was significantly higher than that to cells inoculated with HBV only. Pretreatment of the cells with HBs-S also increased viral DNA levels significantly compared to that in untreated cells. In contrast, HBs-L did not enhance the viral attachment. Enhancement of viral attachment was associated with the attachment of HBs-S to the cells via heparan sulfate. HBs-S also interacted with the viral particle. Furthermore, in chimeric mice with humanized livers, HBs-S enhanced HBV infection.ConclusionsWe demonstrated that HBs-S enhances viral attachment in vitro and viral infection in vivo. HBs-S interacted with heparan sulfate on the cellular surface, and this interaction contributed to the enhancement of viral attachment. These data indicate that HBs-S enhances the viral infection, and may contribute to the high transmissibility of HBV.
Environmental circulation of adenovirus 40/41 and SARS-CoV-2 in the context of the emergence of acute hepatitis of unknown origin
Authors: Wollants Elke , Keyaerts Els , Cuypers Lize , Bloemen Mandy , Thijssen Marijn , Ombelet Sien , Raymenants Joren , Beuselinck Kurt , Laenen Lies , Budts Lore , Pussig Bram , Lagrou Katrien , Van Ranst Marc , André Emmanuel 
Published: June 2022

AbstractThe recent surge of hepatitis of unknown origin in children is hypothesized to be caused by adenovirus 41 and/or SARS-CoV-2 infections. A relatively high proportion of patients testing positive for these viruses concomitantly with the development of acute hepatitis supports this hypothesis. To formally incriminate these viral infections as causative agents of hepatitis, both a plausible physiopathological pathway and supporting epidemiological dynamics in the community need demonstration. In this study, we measured the level of circulation of adenovirus 40/41 and SARS-CoV-2 in the general population of the city of Leuven in Belgium using wastewater monitoring between December 2020 and May 2022 and indoor air sampling in day care centers between November 2021 and May 2022. We also retrospectively analyzed medical records of 12.672 children attending a tertiary hospital draining the same region between January 2019 and April 2022. Our results demonstrate a recent but modest increase in hepatitis of unknown origin concomitant with a surge of circulating adenovirus 41 and SARS-CoV-2 in the general population, including in children under 5.
The landscape of secondary malignancies in cancer survivors and the susceptibility to hereditary multiple cancer syndrome: a Korean nationwide population-based study
Authors: Choi Yoon Young , Lee Myeongjee , Kim Eun Hwa , Lee Jae Eun , Jung Inkyung , Cheong Jae-Ho 
Published: June 2022

ABSTRACTBackgroundCancer survivors and secondary malignancy risk have increased following early diagnosis and advanced cancer treatments; however, secondary malignancy risk in cancer survivors and possibility of genetic susceptibility among young individuals with multiple cancers have scarcely been evaluated. We evaluated the risk of secondary malignancies in cancer survivors by primary cancer type, and the combination of cancer types frequently observed in young patients with multiple cancers.Methods and FindingsPatients diagnosed with cancer, from Korea Health Insurance Review and Assessment database, between January 2009 and December 2010, were followed-up until December 2019. Cancer survivors and those with secondary cancers were defined as having lived >5 years without developing other cancers; and being newly diagnosed with cancer at another site, respectively. To identify possible hereditary multiple cancer syndrome (HMCS), combinations of multiple cancers frequently observed in young individuals compared to older adults were evaluated. Of the 371,181 patients in 3,008,274 person-years of follow-up, 266,241 were cancer survivors; of these 7,348 had secondary cancers (2.76%; 2,759.9 persons/100,000 population), higher than primary cancer risk in general population. The common primary cancer types were those mainly observed as secondary cancer in cancer survivors. Contrarily, higher-risk cancers among those with secondary cancers compared to those in the general population varied by sex and primary cancer type, suggesting the need for tailored cancer screening for cancer survivors. Combinations of well-known hereditary cancer syndrome-related cancer types were mainly observed in younger compared to older patients with multiple cancers, which could be HMCS, including cancer combinations those may be caused by a novel cancer predisposition gene.ConclusionsCancer survivors harbor high and distinctive secondary cancer risk than the general population, necessitating tailored cancer screening in survivors. Genetic screening should be considered for young patients with multiple cancers to validate genetic predisposition.
Evaluation of the efficacy of Lactobacillus-containing feminine hygiene products on vaginal microbiome and genitourinary symptoms in pre- and postmenopausal women: A pilot randomized controlled trial
Authors: Yoshikata Remi , Yamaguchi Michiko , Mase Yuri , Tatsuyuki Ayano , Myint Khin Z. , Ohta Hiroaki 
Published: June 2022

AbstractObjectiveAs estrogen level decreases with aging, the vaginal mucosa gets thinner, and collagen amount decreases. In addition, the population of Lactobacillus in the vagina declines, increasing the risk of atrophic vaginitis, bacterial vaginosis, and genitourinary symptoms in the postmenopausal women. In this study, we evaluated the effects of Lactobacillus-containing feminine hygiene products on vaginal microbiome and genitourinary symptoms in pre- and postmenopausal women.MethodsThis was a pilot randomized controlled trial in 35 premenopausal and 35 postmenopausal healthy women. For 4 weeks, treatment 1 group (14 premenopausal and 16 postmenopausal women) used the Lactobacillus-containing feminine soap and cream, and treatment 2 group (15 premenopausal and 14 postmenopausal women) used Lactobacillus-containing feminine gel in addition to soap and cream. The remaining 6 premenopausal and 5 postmenopausal women served as controls without using any products. We then compared the changes in the vaginal microbiota, genitourinary symptoms, and other related biomarkers after completion of treatment.ResultsVaginal pH and pathogenic flora were reduced in both treatment groups compared to control group. It was more significant in the treatment 2 group of postmenopausal women. Genitourinary symptoms significantly improved in 60% of premenopausal women in treatment 1 group and 81.3% of postmenopausal women in treatment 2 group, compared to control group (0%). Overactive bladder symptom scores were significantly improved after using the products in the postmenopausal women suspected of having overactive bladder.ConclusionThe use of Lactobacillus-containing feminine products was associated with improved vaginal ecosystem and urogenital health compared to control group, especially in those women using feminine gel.
Intraoperative Plasma Proteomic Changes in Cardiac Surgery: In Search of Biomarkers of Post-operative Delirium
Authors: Wiredu Kwame , O’Connor Sean , Monteith Erika , Brauer Brooke , Kettenbach Arminja N. , Frost Hildreth R. , Shaefi Shahzad , Gerber Scott A. 
Published: June 2022

AbstractPurposeDelirium presents a significant healthcare burden. It complicates post-operative care in up to 50% of cardiac surgical patients with worse hospital outcomes, longer hospital stays and higher overall cost of care. Moreover, the nature of delirium following cardiac surgery with cardiopulmonary bypass (CPB) remains unclear, the underlying pathobiology is poorly understood, status quo diagnostic methods are subjective, and diagnostic biomarkers are currently lacking.ObjectiveTo identify diagnostic biomarkers of delirium and for insights into possible neuronal pathomechanisms.Experimental designComparative proteomic analyses were performed on plasma samples from a nested matched cohort of patients who underwent cardiac surgery on CPB. A targeted proteomics strategy was used for validation in an independent set of samples. Biomarkers were assessed for biological functions and diagnostic accuracy.Results47% of subjects demonstrated delirium. Of 3803 total proteins identified and quantified from patient plasma samples by multiplexed quantitative proteomics, 16 were identified as signatures of exposure to CPB, and 11 biomarkers distinguished delirium cases from non-cases (AuROC = 93%). Notable among these biomarkers are C-reactive protein, serum amyloid A-1 and cathepsin-B.Conclusions and clinical relevanceThe interplay of systemic and central inflammatory markers shed new light on delirium pathogenesis. This work suggests that accurate identification of cases may be achievable using a panel of biomarkers.Statement of Clinical RelevanceThe acute implication of delirium is well-documented, yet the true extent of the consequences beyond the immediate post-operative period has yet to be fully known. Despite its impact on the geriatric population, delirium remains underdiagnosed. Correctly identifying cases remain a challenge in clinical practice: the arbitrary and subjective nature of current diagnostic tools, such as the confusion assessment method, underscores the urgent need for diagnostic biomarkers. The clinical usefulness of delirium biomarkers extent beyond the objective identification of cases. Delirium biomarkers will also be useful for risk stratification, long-term follow-up of patients and may offer insights into possible etiologies that underpin the condition. In this report, we found systemic markers of inflammation with well-established association with delirium, as well as new biomarkers that shed new light on the condition. Although validation in a larger cohort is the necessary next step, our efforts lay the groundwork for future studies and highlight new frontiers in delirium research yet to be explored.