bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing transcriptomic re-identification risks using discriminative sequence models
Authors: Sadhuka Shuvom , Fridman Daniel , Berger Bonnie , Cho Hyunghoon 
Published: April 2023

AbstractGene expression data provides molecular insights into the functional impact of genetic variation, for example through expression quantitative trait loci (eQTL). With an improving understanding of the association between genotypes and gene expression comes a greater concern that gene expression profiles could be matched to genotype profiles of the same individuals in another dataset, known as a linking attack. Prior works demonstrating such a risk could analyze only a fraction of eQTLs that are independent due to restrictive model assumptions, leaving the full extent of this risk incompletely understood. To address this challenge, we introduce the discriminative sequence model (DSM), a novel probabilistic framework for predicting a sequence of genotypes based on gene expression data. By modeling the joint distribution over all known eQTLs in a genomic region, DSM improves the power of linking attacks with necessary calibration for linkage disequilibrium and redundant predictive signals. We demonstrate greater linking accuracy of DSM compared to existing approaches across a range of attack scenarios and datasets including up to 22K individuals, suggesting that DSM helps uncover a substantial additional risk overlooked by previous studies. Our work provides a unified framework for assessing the privacy risks of sharing diverse omics datasets beyond transcriptomics.
“Antimicrobial Properties and Physical Characteristics of Essential Oil Extracted fromArtemisia herba albaCollected in El Bayadh, Algeria”
Authors: Dif Mustapha mahmoud , Fatima zohra Djaadane 
Published: April 2023

AbstractArtemisia herba-albais a white mugwort harvested in the Bougtobe region of the El-Bayad province. Essential oils were extracted from the plant using hydrodistillation. The antibacterial study ofArtemisia herba-albaessential oils revealed a significant inhibitory action on the growth of tested microorganisms includingBacillus cereus, Staphylococcus aureus. These results demonstrated significant activity compared to the positive control penicillin, amoxicillin, and spiramycin. Overall, the results showed that the tested essential oil possesses interesting antimicrobial activities, and therefore, opens up new perspectives in the field of natural applications as a promising alternative to chemical products and for industrial exploitation.
WITHDRAWN: LonP1 Drives Proneural Mesenchymal Transition in IDH1-R132H Diffuse Glioma
Authors: Douglas Christopher , Lomeli Naomi , Vu Thao , Pham James , Bota Daniela A. 
Published: April 2023

Withdrawal StatementThe authors have withdrawn their manuscript owing to massive revision and data validation. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Computational pathology infers clinically relevant protein levels and drug response in breast cancer by weakly supervised contrastive learning
Authors: Liu Hui , Xie Xiaodong , Wang Bin 
Published: April 2023

AbstractVisual inspection of histopathology slides via optical microscope is the routine medical examination for clinical diagnosis of tumors. Recent studies have demonstrated that computational pathology not only automate the tumor diagnosis, but also showed great potential to uncover tumor-related genetic alterations and transcriptomic patterns. In this paper, we propose wsi2rppa, a weakly supervised contrastive learning framework to infer the protein levels of tumor biomarkers from whole slide images (WSIs) in breast cancer. We firstly conducted contrastive learning-based pre-training on tessellated tiles to extract histopathological features, which are then aggregated by attention pooling and adapted to downstream tasks. Our extensive experiments showed that our method achieved state-of-the-art performance in tumor diagnostic task, and also performed well in predicting clinically relevant protein levels and drug response. To show the model interpretability, we spatially visualized the WSIs colored the tiles by their attention scores, and found that the regions with high scores were highly consistent with the tumor and necrotic regions annotated by a 10-year experienced pathologist. Moreover, spatial transcriptomic data further verified that the heatmap generated by attention scores agree greatly with the spatial expression landscape of two typical tumor biomarker genes. In particular, our method achieved 0.79 AUC value in predicting the response of breast cancer patients to the drug trastuzumab treatment. These findings showed the remarkable potential of deep learning-based morphological feature is very indicative of clinically relevant protein levels, drug response and clinical outcomes.
Evaluation of the disease-modifying effects of Aureobasidium pullulans AFO-202 strain produced Beta-Glucan in Parkinson’s disease – Results of a pilot clinical study
Authors: Vetrievel Chockanathan , Nithyanandam Allimuthu , Srinivasan Subramaniam , Bharatidasan Sudhakar S , Dedeepiya Vidyasagar Devaprasad , Ikewaki Nobunao , Iwasaki Masaru , Senthilkumar Rajappa , Preethy Senthilkumar , Abraham Samuel JK 
Published: April 2023

AbstractThe aetiology of Parkinson’s disease (PD) has been linked to the aggregation and spread of misfolded alpha-synuclein via the gut-brain axis. We previously reported the effects of a biological response modifier, beta-glucan, produced by the AFO-202 strain ofAureobasidium Pullulans, which improves clinical symptoms and controls gutEnterobacteriaceaeassociated with curli and amyloid-alpha-synuclein production. In this study, we report the effects of beta-glucan on PD. Eight patients with PD were recruited, five of whom completed the study. Each participant was administered 3 g of AFO-202 B-glucan orally daily for 90 days in addition to their regular prescription drugs. Pre- and post-study comparison revealed that the mean UPDRS decreased from 43.25 ± 13.75 at baseline to 40 ± 13.65 post intervention. Improvements in cognition, walking and balance, postural stability, and constipation scales were observed. The mean constipation severity score decreased from 3 ± 1.73 to 1.75 ± 0.43 post intervention. The serum creatinine kinase levels decreased and the blood glucose and lipid levels normalised. The MRI Parkinson’s index (MRPI) improved in one patient. This safe AFO-202 B-glucan produced beneficial disease-modifying improvements in the UPDRS and MRI that were clinically significant in the short timeframe of 90 days. Further validation in larger, longer-term clinical trials will help confirm the use of beta-glucan as a potential adjuvant treatment for PD which may pave way for future evaluations of these beta-glucans in other synculeinopathies as well Lewy-body related pathogenesis.
Whole-brain deactivations precede uninduced mind-blanking reports
Authors: Boulakis Paradeisios Alexandros , Mortaheb Sepehr , Calster Laurens van , Majerus Steve , Demertzi Athena 
Published: April 2023

AbstractMind-blanking (MB) is termed as the inability to report our immediate-past mental content. In contrast to mental states with reportable content, such as mind-wandering or sensory perceptions, the neural correlates of MB started getting elucidated only recently. A notable particularity that pertains to MB studies is the way MB is instructed for reporting, like by deliberately asking participants to “empty their minds”. Such instructions were shown to induce fMRI activations in frontal brain regions, typically associated with metacognition and self-evaluative processes, suggesting that MB may be a result of intentional mental content suppression. Here, we aim at examining this hypothesis by determining the neural correlates of MB without induction. Using fMRI combined with experience-sampling in 31 participants (22 female), univariate analysis of MB reports revealed deactivations in occipital, frontal, parietal, and thalamic areas, but no activations in prefrontal regions. These findings were confirmed using Bayesian region-of-interest analysis on areas previously shown to be implicated in induced MB, where we report evidence for frontal deactivations during MB reports compared to other mental states. Contrast analysis between reports of MB and content-oriented mental states also revealed deactivations in the left angular gyrus. We propose that these effects characterize a neuronal profile of MB, where key thalamocortical nodes are unable to communicate and formulate reportable content. Collectively, we show that study instructions for MB lead to differential neural activation. These results provide mechanistic insights linked to the phenomenology of MB and point to the possibility of MB being expressed in different forms.
Marine transmissible cancer navigates urbanised waters, threatening to spillover
Authors: Hammel M. , Touchard F. , Burioli E. A. V. , Paradis L. , Cerqueira F. , Chailler E. , Bernard I. , Cochet H. , Simon A. , Thomas F. , Destoumieux-Garzón D. , Charrière G. M. , Bierne N. 
Published: April 2023

AbstractInter-individual transmission of cancer cells represents a unique form of microparasites increasingly reported in marine bivalves. In this study, we sought to understand the ecology of the propagation ofMytilus trossulusBivalve Transmissible Neoplasia 2 (MtrBTN2), a transmissible cancer affecting fourMytilusmussel species worldwide. We investigated the prevalence of MtrBTN2 in the mosaic hybrid zone ofM. edulisandM. galloprovincialisalong the French Atlantic coast, sampling contrasting natural and anthropogenic habitats. We observed a similar prevalence in both species, likely due to the spatial proximity of the two species in this region. Our results showed that ports had higher prevalence of MtrBTN2, with a possible hotspot observed at a shuttle landing dock. No cancer was found in natural beds except for two sites close to the hotspot, suggesting spillover. Ports may provide favourable conditions for the transmission of MtrBTN2, such as high mussel density, stressful conditions, sheltered and confined shores, or buffered temperatures. Ships may also spread the disease through biofouling. Our results suggest ports may serve as epidemiological hubs, with maritime routes providing artificial gateways for MtrBTN2 propagation. This highlights the importance of preventing biofouling on docks and ship hulls to limit the spread of marine pathogens hosted by fouling species.
Targeting the catalytic activity of HDAC1 in T cells protects against experimental autoimmune encephalomyelitis
Authors: Zhu Ci , Stolz Valentina , Simonovic Natalija , Al-Rubaye Osamah , Vcelkova Terezia , Moos Verena , Hess Lena , Hagelkruys Astrid , Madern Moritz , Reiter Wolfgang , Meixner Arabella , Bock Christoph , Hartl Markus , Ellmeier Ellmeier , Seiser Christian 
Published: April 2023

AbstractHistone deacetylases are key epigenetic regulators that control T cell-mediated immunity. A T cell-specific deletion ofHdac1(HDAC1cKO) protects mice against experimental autoimmune encephalomyelitis (EAE). However, it remains elusive whether inhibition of HDAC1 enzymatic activity, which could be achieved therapeutically by HDAC1 inhibitor treatment, is sufficient to block EAE induction. In order to address this question, we generated a novel mouse strain that expresses catalytically inactive HDAC1 (HDAC1Off) from theRosa26locus in HDAC1cKOCD4+T cells to mimic selective inhibition of HDAC1 enzymatic activityin vivo. Mice expressing wildtype HDAC1 in HDAC1cKOCD4+T cells (HDAC1On) were generated as corresponding controls. In contrast to HDAC1Onmice, HDAC1Offmice did not develop EAE, and this correlated with diminished leukocyte CNS infiltration. HDAC1OffCD4+T cells in the CNS displayed a severe reduction of IFNγ, IL-17A and TNFα proinflammatory cytokine expression, andin vivoactivated HDAC1OffCD4+T cells downregulated gene sets associated with T cell activation, cytokine expression and cell migration. This indicates impaired effector functions of HDAC1OffCD4+T cells. Taken together, our study demonstrates that the inhibition of the catalytic activity of HDAC1 in T cells is sufficient to achieve a clinical benefit in EAE disease development. This raises the translational perspective of pharmacological HDAC1 inhibition for treating human T cell-mediated autoimmune diseases.HighlightsSuccessful generation of a novel mouse model that expresses enzymatic-inactive HDAC1 to mimic HDAC1 inhibitor treatmentin vivo.Mice expressing enzymatically inactive HDAC1 instead of WT HDAC1 in T cells do not develop EAE and display diminished leukocyte CNS infiltration.In vivoactivated CD4+T cells expressing enzymatic inactive HDAC1 downregulate pathways important for T cell activation, cytokine expression and cell migration.Demonstrate the proof-of-principle that targeting the enzymatic activity of HDAC1 is a promising treatment strategy for autoimmune diseases.
Data-Driven Modelling of Gene Expression States in Breast Cancer and their Prediction from Routine Whole Slide Images
Authors: Dawood Muhammad , Eastwood Mark , Jahanifar Mostafa , Young Lawrence , Ben-Hur Asa , Branson Kim , Jones Louise , Rajpoot Nasir , Minhas Fayyaz ul Amir Afsar 
Published: April 2023

SummaryIdentification of gene expression state of a cancer patient from routine pathology imaging and characterization of its phenotypic effects have significant clinical and therapeutic implications. However, prediction of expression of individual genes from whole slide images (WSIs) is challenging due to co-dependent or correlated expression of multiple genes. Here, we use a purely data-driven approach to first identify groups of genes with co-dependent expression and then predict their status from (WSIs) using a bespoke graph neural network. These gene groups allow us to capture the gene expression state of a patient with a small number of binary variables that are biologically meaningful and carry histopathological insights for clinically and therapeutic use cases. Prediction of gene expression state based on these gene groups allows associating histological phenotypes (cellular composition, mitotic counts, grading, etc.) with underlying gene expression patterns and opens avenues for gaining significant biological insights from routine pathology imaging directly.Graphical AbstractHighlightsData-driven discovery of co-expressing gene groups in breast canerHistological imaging based prediction of gene groups via deep learningIdentification of phenotypic correlates of gene-expression in histological imagingClinical and therapeutic impact of gene groups and their visual patterns identified
EOGT Enables Residual Notch Signaling in Mouse Intestinal Cells Lacking POFUT1
Authors: Nauman Mohd , Varshney Shweta , Choi Jiahn , Augenlicht Leonard H. , Stanley Pamela 
Published: April 2023

AbstractNotch signaling determines cell fates in mouse intestine. Notch receptors contain multiple epidermal growth factor-like (EGF) repeats modified by O-glycans that regulate Notch signaling. Conditional deletion of protein O-fucosyltransferase 1 (Pofut1) substantially reduces Notch signaling and markedly perturbs lineage development in mouse intestine. However, mice with inactivatedPofut1are viable, whereas complete elimination of Notch signaling in intestine is lethal. Here we investigate whether residual Notch signaling enabled by EOGT permits mice lackingPofut1in intestine to survive. Mice globally lackingEogtalone were grossly unaffected in intestinal development. In contrast, mice lacking bothEogtandPofut1died at ∼28 days after birth with greater loss of body weight, a greater increase in the numbers of goblet and Paneth cells, and greater downregulation of Notch target genes, compared toPofut1deletion alone. These data establish that both O-fucose and O-GlcNAc glycans are fundamental to Notch signaling in the intestine and provide new insights into roles for O-glycans in regulating Notch ligand binding. Finally, EOGT and O-GlcNAc glycans provide residual Notch signaling and support viability in mice lackingPofut1in the intestine.
A maturation defective HIV-1 activates cGAS
Authors: Sumner Rebecca P. , Blest Henry , Lin Meiyin , Maluquer de Motes Carlos , Towers Greg J. 
Published: April 2023

AbstractBackgroundDetection of viruses by host pattern recognition receptors induces the expression of type I interferon (IFN) and IFN-stimulated genes (ISGs), which suppress viral replication. Retroviruses such as HIV-1 are subject to sensing by both RNA and DNA sensors, and whether there are any particular features of the viral genome or reverse transcripts that facilitate or enhance this sensing is currently unknown.ResultsWhilst investigating the determinants of innate detection of HIV-1 we noticed that infection of THP-1 cells or primary macrophages with a virus expressing Gag fused to a reporter gene (luciferase or GFP) induced a robust IFN and ISG response that was not observed with an equivalent virus with similar genome length and composition, but expressing wild-type Gag. Innate immune activation by Gag-fusion HIV-1 was dependent on reverse transcription and DNA sensor cGAS, suggesting activation of an IFN response by viral DNA. Further investigation of the Gag-fusion viral particles revealed maturation defects, as evidenced by incomplete Gag cleavage and a diminished capacity to saturate restriction factor TRIM5α, likely due to aberrant particle formation. We propose that expression of the Gag fusion protein disturbs the correct cleavage and maturation of wild-type Gag, yielding viral particles that are unable to effectively shield viral DNA from detection by innate sensors including cGAS.ConclusionsThese data highlight the crucial role of capsid in innate evasion and support growing literature that disruption of Gag cleavage and capsid formation induces a viral DNA- and cGAS-dependent innate immune response. Together these data demonstrate a protective role for capsid and suggest that antiviral activity of capsid-targeting antivirals may benefit from enhanced innate and adaptive immunityin vivo.
During heat stress inMyxococcus xanthus, the CdbS PilZ domain protein, along with two PilZ-DnaK chaperones, perturbs chromosome organization and accelerates cell death
Authors: Seidel Michael , Skotnicka Dorota , Glatter Timo , Søgaard-Andersen Lotte 
Published: April 2023

AbstractC-di-GMP is a bacterial second messenger that regulates diverse processes in response to environmental or cellular cues. The nucleoid-associated protein (NAP) CdbA inMyxococcus xanthusbinds c-di-GMP and DNA in a mutually exclusive mannerin vitro. CdbA is essential for viability, and CdbA depletion causes defects in chromosome organization, leading to a block in cell division and, ultimately, cell death. Most NAPs are not essential; therefore, to explore the paradoxicalcdbAessentiality, we isolated suppressor mutations that restored cell viability without CdbA. Most mutations mapped tocdbS, which encodes a stand-alone c-di-GMP binding PilZ domain protein, and caused loss-of-function ofcdbS. Cells lacking CdbA and CdbS or only CdbS were fully viable and had no defects in chromosome organization. CdbA depletion caused post-transcriptional upregulation of CdbS accumulation, and this CdbS over-accumulation was sufficient to disrupt chromosome organization and cause cell death. CdbA depletion also caused increased accumulation of CsdK1 and CsdK2, two unusual PilZ-DnaK chaperones. During CdbA depletion, CsdK1 and CsdK2, in turn, stabilized CdbS, thereby enabling its increased accumulation and toxicity. Moreover, we demonstrate that heat stress, possibly involving an increased cellular c-di-GMP concentration, induces the CdbA/CsdK1/CsdK2/CdbA system, causing a CsdK1- and CsdK2-dependent increase in CdbS accumulation. Thereby this system accelerates heat stress-induced chromosome mis-organization and cell death. Collectively, this work describes a unique system that contributes to regulated cell death inM. xanthusand suggests a link between c-di-GMP signaling and regulated cell death in bacteria.Author summaryThe nucleotide-based second messenger c-di-GMP in bacteria controls numerous processes in response to environmental or cellular cues. Typically, these processes are related to lifestyle transitions between motile and sessile behaviors. However, c-di-GMP also regulates other processes. InMyxococcus xanthus, CdbA is a DNA-binding and nucleoid-associated protein that helps to organize the large chromosome. CdbA binds c-di-GMP and DNA in a mutually exclusive manner. While other nucleoid-associated proteins are not essential, CdbA is essential. Here, we show that the crucial function of CdbA is to maintain the level of the c-di-GMP-binding PilZ-domain protein CdbS appropriately low. The CdbS level is not only increased upon depletion of CdbA but also in response to heat stress. Under both conditions, the increased CdbS level perturbs chromosome organization and ultimately causes cell death. The CdbA/CdbS system represents a unique system that contributes to regulated cell death inM. xanthusand suggests a link between c-di-GMP signaling and regulated cell death.
Ultraconformable cuff implants for long-term bidirectional interfacing of peripheral nerves at sub-nerve resolutions
Authors: Carnicer-Lombarte Alejandro , Boys Alexander J. , Güemes Amparo , Gurke Johannes , Velasco-Bosom Santiago , Hilton Sam , Barone Damiano G. , Malliaras George G. 
Published: April 2023

AbstractImplantable devices interfacing with peripheral nerves exhibit limited longevity and resolution. Poor nerve-electrode interface quality, invasive surgical placement and development of foreign body reaction combine to limit research and clinical application of these devices. Here, we develop cuff implants with an ultraconformable design that achieve high-quality and stable interfacing with nerves in chronic implantation scenarios. When implanted in sensorimotor nerves of the arm in awake rats for 21 days, the devices recorded nerve action potentials with fascicle-specific resolution and extracted from these the conduction velocity and direction of propagation. The ultraconformable cuffs exhibited high biocompatibility, producing lower levels of fibrotic scarring than clinically equivalent PDMS silicone cuffs. In addition to recording nerve activity, the devices were able to modulate nerve activity at sub-nerve resolution to produce a wide range of paw movements. The developed implantable devices represent a platform enabling new forms of fine nerve signal sensing and modulation, with applications in physiology research and closed-loop therapeutics.
Mapping lineage-traced cells across time points with moslin
Authors: Lange Marius , Piran Zoe , Klein Michal , Spanjaard Bastiaan , Klein Dominik , Junker Jan Philipp , Theis Fabian J. , Nitzan Mor 
Published: April 2023

AbstractSimultaneous profiling of single-cell gene expression and lineage history holds enormous potential for studying cellular decision-making beyond simpler pseudotime-based approaches. However, it is currently unclear how lineage and gene expression information across experimental time points can be combined in destructive experiments, which is particularly challenging for in-vivo systems. Here we present moslin, a Fused Gromov-Wasserstein-based model to couple matching cellular profiles across time points. In contrast to existing methods, moslin leverages both intra-individual lineage relations and inter-individual gene expression similarity. We demonstrate on simulated and real data that moslin outperforms state-of-the-art approaches that use either one or both data modalities, even when the lineage information is noisy. OnC. elegansembryonic development, we show how moslin, combined with trajectory inference methods, predicts fate probabilities and putative decision driver genes. Finally, we use moslin to delineate lineage relationships among transiently activated fibroblast states during zebrafish heart regeneration. We anticipate moslin to play a crucial role in deciphering complex state change trajectories from lineage-traced single-cell data.