bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of digital Early Warning Score (NEWS2) in a cardiac specialist setting: retrospective cohort study
Authors: Alhmoud Baneen , Bonnici Timothy , Melley Daniel , Patel Riyaz , Banerjee Amitava 
Published: June 2022

AbstractIntroductionPatients with Cardiovascular diseases (CVD) are at significant risk of developing critical events. Early warning scores are recommended for early recognition and rapid response to deteriorating patients, yet their performance has been poorly studied in cardiac care settings. Standardisation and integrated National early warning score (NEWS2) in EHRs are recommended but their evaluation in specialist settings is limited.ObjectiveTo investigate the performance of digital NEWS2 in predicting critical events: death, ICU admission, Cardiac arrest, and medical emergencies.MethodsRetrospective cohort analysisStudy cohortIndividuals admitted with cardiovascular disease diagnoses in 2020 and patients with positive COVID-19.MeasuresWe tested the ability of NEWS2 in predicting death, ICU admission, cardiac arrest, and medical emergency from admission and within 24 hours before the event. NEWS2 was supplemented with age and cardiac rhythm and investigated. We used logistic regression analysis with the area under the receiver operating curve (AUC) to measure discrimination.ResultsIn 6143 patients admitted under cardiac speciality, NEWS2 showed moderate to low predictive accuracy (AUC: 0.63, 0.56, 0.7& 0.63; 95% CI). Supplemented NEWS2 with age showed no improvement while age and cardiac rhythm improved discrimination (AUC: 0.75, 0.84, 0.95 & 0.94; 95%CI). Improved Performance was found of NEWS2 for COVID-19 cases with age (AUC: 0.96, 0.7, 0.87& 0.88; 95% CI).ConclusionThe performance of NEWS2 in patients with CVD is suboptimal, and fair for patients with COVID-19 to predict deterioration early. Adjustment with variables that strongly correlate with critical cardiovascular outcomes, i.e. cardiac rhythm, can improve the early scoring models. There is a need to define critical endpoints, engagement with clinical experts in development of models and further validation and implementation studies of EHR-integrated EWS in cardiac specialist settings.
Addition of losartan to FOLFORINOX and chemoradiation downregulates pro-invasion and immunosuppression-associated genes in locally advanced pancreatic cancer
Authors: Boucher Yves , Posada Jessica M. , Subudhi Sonu , Rosario Spencer R. , Gu Liqun , Kumar Ashwin S. , Kumra Heena , Mino-Kenudson Mari , Talele Nilesh P. , Duda Dan G. , Fukumura Dai , Wo Jennifer Y. , Clark Jeffrey W. , Ryan David P. , Castillo Carlos Fernandez-Del , Hong Theodore S. , Pittet Mikael J. , Jain Rakesh K. 
Published: June 2022

AbstractPurposeAdding losartan to FOLFIRINOX (FFX) chemotherapy followed by chemoradiation (CRT) resulted in 61% R0 surgical resection in our phase II trial in patients with locally advanced pancreatic cancer (LAPC). Here we identify potential mechanisms of benefit by assessing the effects of neoadjuvant losartan+FFX+CRT versus FFX+CRT on the stromal tumor microenvironment.Experimental DesignWe performed a gene expression analysis of RNA extracted from pancreatic cancer tissue sections and immunofluorescence for cancer cells and immune cells using archived surgical samples from patients treated with losartan+FFX+CRT (NCT01591733), FFX+CRT (NCT01591733) or surgery upfront, without any neoadjuvant therapy. We then assessed whether certain gene sets could stratify the overall survival (OS) of patients.ResultsNeoadjuvant losartan+FFX+CRT and FFX+CRT increased the expression of genes linked to vascular normalization, transendothelial migration of leukocytes, T cell activation and cytolytic activity, and dendritic cell (DC) related genes versus no neoadjuvant treatment. In comparison to FFX+CRT, losartan+FFX+CRT downregulated pro-invasion, immunosuppression, and M2 macrophages related genes, and upregulated genes associated with tumor suppression, including the p53 pathway. Furthermore, immunostaining revealed significantly less residual disease in lesions treated with losartan+FFX+CRT versus FFX+CRT. Losartan+FFX+CRT also reduced CD4+FOXP3+regulatory T cells in PDAC lesions with a complete/near complete response. OS was associated with DC and antigen presentation genes for patients treated with FFX+CRT, and with immunosuppression and invasion genes or DC- and blood vessel-related genes for those treated with losartan+FFX+CRT.ConclusionsAdding losartan to FFX+CRT reduced pro-invasion and immunosuppression related genes, which were associated with improved treatment outcomes in patients with LAPC.
High overexploitation risk due to management shortfall in highly traded requiem sharks
Authors: Sherman C. Samantha , Digel Eric D. , Zubick Patrick , Eged Jonathan , Haque Alifa B. , Matsushiba Jay H. , Simpfendorfer Colin A. , Sant Glenn , Dulvy Nicholas K. 
Published: June 2022

ABSTRACTMost of the international trade in fins (and likely meat too) is derived from requiem sharks (family Carcharhinidae), yet trade in only two of the 56 species is currently regulated. Here, we quantify catch, trade, and the shortfall in national and regional fisheries management (M-Risk) for all 56 requiem shark species based on 831 assessments across 30 countries and four Regional Fisheries Management Organisations (RFMOs). Requiem sharks comprise over half (60%) of the annual reported global chondrichthyan catch with most species (86%) identified in the international fin trade. Requiem sharks are inadequately managed by fisheries, with an average M-Risk of half (50%) of an ideal score, consequently 70% of species are threatened globally. The high catch and trade volume and shortfall in management of these iconic species requires a global integrated improvement in fisheries management, supported by regulating international trade to sustainable levels.
β-catenin obstructs γδ T cell immunosurveillance in colon cancer through loss of BTNL expression
Authors: Suzuki Toshiyasu , Kilbey Anna , Ridgway Rachel A. , Hayman Hannah , Bryne Ryan , Rodríguez Nuria Casa , Georgakopoulou Anastasia , Chen Lei , Verzi Michael , Gay David , Vázquez Ester G. , Belnoue-Davis Hayley L. , Gilroy Kathryn , Køstner Anne Helene , Kersten Christian , Thuwajit Chanitra , Andersen Ditte , Wiesheu Robert , Jandke Anett , Roberts Natalie , Blyth Karen , Roseweir Antonia , Leedham Simon J. , Dunne Philip D. , Edwards Joanne , Hayday Adrian , Sansom Owen J. , Coffelt Seth B. 
Published: June 2022

ABSTRACTWNT/β-catenin signaling endows cancer cells with proliferative capacity and immune-evasive functions that impair anti-cancer immunosurveillance by conventional, cytoxtoic T cells. However, the impact of dysregulated WNT signalling on unconventional, tissue-resident T cells, specifically in colon cancer is unknown. Here, we show that cancer cells in Apc-mutant mouse models escape immunosurveillance from gut-resident intraepithelial lymphocytes (IELs) expressing γδ T cell receptors (γδTCRs). Analysis of late-stage tumors from mice and humans revealed that γδIELs are largely absent from the tumor microenvironment, and that butyrophilin-like (BTNL) molecules, which can critically regulate γδIEL through direct γδTCR-interactions, are also downregulated. We could attribute this to β-catenin stabilization, which rapidly decreased expression of the transcription factors, HNF4A and HNF4G, that we found to bind promoter regions of Btnl genes, thereby driving their expression in normal gut epithelial cells. Indeed, inhibition of β-catenin signaling restored Btnl1 gene expression and γδ T cell infiltration into tumors. These observations highlight an immune-evasion mechanism specific to WNT-driven colon cancer cells that disrupts γδIEL immunosurveillance and furthers cancer progression.
Bento: A toolkit for subcellular analysis of spatial transcriptomics data
Authors: Mah Clarence K. , Ahmed Noorsher , Lopez Nicole , Lam Dylan , Monell Alexander , Kern Colin , Han Yuanyuan , Prasad Gino , Cesnik Anthony J. , Lundberg Emma , Zhu Quan , Carter Hannah , Yeo Gene W. 
Published: June 2022

AbstractThe spatial organization of molecules in a cell is essential for performing their functions. Spatial transcriptomics technologies have opened the door to characterization of cellular and subcellular organization. While current computational methods focus on discerning tissue architecture, cell-cell interactions and spatial expression patterns, these approaches are limited to investigating spatial variation at the multicellular scale. We present Bento, a Python toolkit that fully takes advantage of single-molecule information to enable spatial analysis at the subcellular scale. Bento ingests molecular coordinates and segmentation boundaries to perform three fundamental analyses: defining subcellular domains, annotating localization patterns, and quantifying gene-gene colocalization. To demonstrate the toolkit, we apply these methods to a variety of datasets including U2-OS cells (MERFISH), 3T3 cells (seqFISH+), and treated cardiomyocytes (Molecular Cartography). We quantify RNA localization changes in cardiomyocytes identifying mRNA depletion of critical cardiac disease-associated genes RBM20 and CACNB2 from the endoplasmic reticulum upon doxorubicin treatment. The Bento package is a member of the open-source Scverse ecosystem, enabling integration with other single-cell omics analysis tools.
Sodium ion regulates liquidity of biomolecular condensates in hyperosmotic stress response
Authors: Morishita Kazuhiro , Watanabe Kengo , Naguro Isao , Ichijo Hidenori 
Published: June 2022

SummaryBiomolecular condensates are membraneless structures formed through phase separation. Recent studies have demonstrated that the material properties of biomolecular condensates are crucial for their biological functions and pathogenicity. However, the phase maintenance of biomolecular condensates in cells remains elusive. Here, we show that sodium ion (Na+) influx regulates the condensate liquidity under hyperosmotic stress. The fluidity of ASK3 condensates increases at the high intracellular Na+ concentration derived from extracellular hyperosmotic solution. Moreover, we identified TRPM4 as a cation channel that allows Na+ influx under hyperosmotic stress. TRPM4 inhibition causes the liquid-to-solid phase transition of ASK3 condensates, leading to impairment of the ASK3 osmoresponse. In addition to ASK3 condensates, intracellular Na+ widely regulates the condensate liquidity and aggregate formation of biomolecules, including DCP1A, TAZ and polyQ-protein, under hyperosmotic stress. Our findings demonstrate that changes in Na+ contribute to the cellular stress response via liquidity maintenance of biomolecular condensates.
SonoMyoNet: A Convolutional Neural Network for Predicting Isometric Force From Highly Sparse Ultrasound Images
Authors: Kamatham Anne Tryphosa , Alzamani Meena , Dockum Allison , Sikdar Siddhartha , Mukherjee Biswarup 
Published: June 2022

AbstractUltrasound imaging or sonomyography has been found to be a robust modality for sensing muscle activity due to its ability to directly image deep-seated muscles while providing superior spatiotemporal specificity compared to surface electromyography-based techniques. Quantifying the morphological changes during muscle activity involves computationally expensive approaches to track muscle anatomical structures or extracting features from B-mode images and A-mode signals. In this paper an offline regression convolutional neural network (CNN) called SonoMyoNet for estimating continuous isometric force from sparse ultrasound scanlines has been presented. SonoMyoNet learns features from a few equispaced scanlines selected from B-mode images and utilizes the learned features to accurately estimate continuous isometric force. The performance of SonoMyoNet was evaluated by varying the number of scanlines to simulate the placement of multiple single element ultrasound transducers in a wearable system. Results showed that SonoMyoNet could accurately predict isometric force with just four scanlines and is immune to speckle noise and shifts in the scanline location. Thus, the proposed network reduces the computational load involved in feature tracking algorithms and estimates muscle force from global features of sparse ultrasound images.
Microglia and meningeal macrophages depletion delay the onset of experimental autoimmune encephalomyelitis
Authors: Montilla Alejandro , Zabala Alazne , Er-Lukowiak Marco , Rissiek Björn , Magnus Tim , Rodriguez-Iglesias Noelia , Sierra Amanda , Matute Carlos , Domercq María 
Published: June 2022

ABSTRACTIn multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated the influence of microglia in EAE using the colony stimulating factor 1 receptor (CSF-1R) inhibitor, PLX5622, to deplete microglial population andCcr2RFP/+fmsEGFP/+mice, to distinguish peripheral macrophages and microglia. PLX5622 treatment depleted microglia and meningeal macrophages, and provoked a massive infiltration of CCR2+macrophages into demyelinating lesions and spinal cord parenchyma. PLX5622 treatment did not alter EAE chronic phase. In contrast, microglia and meningeal macrophages depletion reduced the expression of CD80 co-stimulatory molecule in dendritic and myeloid cells and reduced T cell reactivation and proliferation in the spinal cord parenchyma, inducing a significant delay in EAE onset. Altogether, these data points to a specific role of CNS microglia meningeal macrophages in antigen presentation and T cell reactivation at initial stages of the EAE model.
Determination of secretion type associated motifs from pathogenic protein sequences
Authors: Özcan Orhan , Çelik Gökalp , Sert Seren , Özcengiz Gülay , Sezerman O. Uğur 
Published: June 2022

AbstractCurrently, potential vaccine candidates are determined using protein localization predictors to identify surface or secreted protein sequences. The pathogenic bacterial sequences constitute only a tiny percentage of this database. They search for general motifs found in bacteria and miss out on pathogen-specific motifs, which is crucial for identifying vaccine candidates. We developed a motif search algorithm derived from pathogenic bacterial sequences in this work. Using this method, we identified secretion motifs of pathogenic bacteria for six different secretion pathways and non-specific secretion motifs. To this end, we established a database of immunogenic sequences from patented vaccine sequences, AntigenDb, and PUB-MED. The motifs are filtered out according to their presence in a cytoplasmic dataset to keep motifs that are present only in secreted sequences. These sequences are validated on newly identified novel vaccine candidates from 20 pathogenic bacterial immunoproteomics data.
Pinpointing the distinctive impacts of ten cover crop species on the resident and active fractions of the soil microbiome
Authors: Cazzaniga Sara Giulia , Braat Lize , van den Elsen Sven , Lombaers Carin , Visser Johnny , Maciá-Vicente Jose G. , Postma Joeke , Mommer Liesje , Helder Johannes 
Published: June 2022

AbstractCover crops are used in agriculture to minimise soil erosion, prevent nutrient leaching and increase soil organic matter content. Cover crops can also be grown to stimulate the soil microbial community to improve soil biological conditions. Despite their widespread use, little is known about the impact of different cover crop species on the composition and activity of the soil microbiome. Here we investigate the effect of distinct cover crop species on the rhizosphere microbiome and to characterise both the resident (DNA-based) and the active (RNA-based) fractions of the bacterial, fungal, protist and metazoan communities in the cover crops rhizosphere. We conducted a field experiment using 70-litre bottomless containers in which we grew ten monocultures of commonly used cover crop species belonging to five plant families, and an unplanted control treatment (fallow). The total DNA and RNA were extracted from soil and the bacterial, fungal, protistan and metazoan communities were characterized using Illumina MiSeq sequencing. We found that all cover crop species significantly impacted the resident and active microbial community composition. Moreover, cover crops showed distinct selection strengths on their rhizospheres. Together with borage (Boraginaceae), oilseed radish (Brassicaceae) was shown to provoke the strongest microbial shifts, in part attributable to a promotion of the bacterial family Pseudomonadaceae and a repression of Microascaceae in the rhizosphere. Lentil (Fabaceae) showed enrichment in fungal taxa, including Trichocomaceae and fungal members of the Glomerales order, whereas black oat, hybrid ryegrass (both Poaceae) and marigold (Asteraceae) induced relatively mild changes in the soil microbial communities. Predominantly, differences in selection strengths were consistent among the four organismal groups under investigation and were observed in both the active and resident communities. Our work provides a broad baseline for the effects of cover crops on four organismal groups, which may facilitate future cover crop selection to advance soil health.
ClinCNV: multi-sample germline CNV detection in NGS data
Authors: Demidov German , Sturm Marc , Ossowski Stephan 
Published: June 2022

AbstractGermline copy number variants (CNVs) are a common source of genomic variation involved in many genetic disorders, and their detection is crucial for clinical molecular diagnostics. Genomic microarrays, quantitative polymerase chain reaction (qPCR), and multiplex ligation-dependent probe amplification (MLPA) have been widely used for CNV detection in clinics for many years. Similarly, next-generation sequencing (NGS) applications such as whole-genome sequencing (WGS) and whole-exome sequencing (WES) are well-established, highly accurate techniques for the detection of single nucleotide variants (SNVs) and small insertions and deletions (indels). However, CNV detection using NGS remains challenging due to short read lengths, smaller than CNVs sizes. CNV detection using read coverage depths summarized in genomic regions is affected by various biases that arise during the library preparation and sequencing. We have developed a novel strategy for detecting CNVs, implemented in the tool ClinCNV (freely available on https://github.com/imgag/ClinCNV). ClinCNV does multi-sample normalization and CNV calling, using an original algorithm taking the best from the circular binary segmentation method and Hidden Markov model-based approaches. Here, we describe the methods and discuss the results obtained by applying ClinCNV to thousands of clinical WES, WGS, and shallow-WGS samples in various clinical and research settings.
Death-associated protein kinase 3 (DAPK3) regulates the myogenic reactivity of cerebral arterioles
Authors: Turner Sara R. , Carlson David A. , Chappellaz Mona , Sutherland Cindy , Haystead Timothy A.J. , Cole William C. , MacDonald Justin A. 
Published: June 2022

ABSTRACTThe vascular smooth muscle (VSM) of resistance blood vessels displays intrinsic autoregulatory responses to increased intraluminal pressure, the myogenic response. In the brain, the myogenic responses of cerebral arterioles are critical to homeostatic blood flow regulation. Here we provide the first evidence to link the death-associated protein kinase 3 (DAPK3) to the myogenic response of rat and human cerebral arterioles. DAPK3 is a Ser/Thr kinase involved in Ca2+− sensitization mechanisms of VSM contraction. Ex vivo administration of a specific DAPK3 inhibitor (i.e., HS38) could attenuate vessel constrictions invoked by serotonin as well as intraluminal pressure elevation. The HS38-dependent dilation was not associated with any change in myosin light chain (LC20) phosphorylation. The results suggest that DAPK3 does not regulate Ca2+ sensitization pathways during the myogenic response of cerebral vessels but rather operates to control the actin cytoskeleton. Finally, a slow return of myogenic tone was observed during the sustained exposure of cerebral arterioles to a suite of DAPK3 inhibitors. Recovery of tone was associated with greater LC20 phosphorylation that suggests intrinsic signaling compensation in response to attenuation of DAPK3 activity. The translational importance of DAPK3 to the human cerebral vasculature was noted, with robust expression of the protein kinase and significant HS38-dependent attenuation of myogenic reactivity found for human pial vessels.
Combinatorial encoding of odors in the mosquito antennal lobe
Authors: Singh Pranjul , Goyal Shefali , Gupta Smith , Garg Sanket , Tiwari Abhinav , Rajput Varad , Bates Alexander Shakeel , Gupta Arjit Kant , Gupta Nitin 
Published: June 2022

AbstractAmong the cues that a mosquito uses to find a host for blood-feeding, the smell of the host plays an important role. Previous studies have shown that host odors contain hundreds of chemical odorants, which are detected by different receptors on the peripheral sensory organs of mosquitoes. But how individual odorants are encoded by downstream neurons in the mosquito brain is not known. We developed an in vivo preparation for patch-clamp electrophysiology to record from projection neurons and local neurons in the antennal lobe of Aedes aegypti. Combining intracellular recordings with dye-fills, morphological reconstructions, and immunohistochemistry, we identify different sub-classes of antennal lobe neurons and their putative interactions. Our recordings show that an odorant can activate multiple neurons innervating different glomeruli, and that the stimulus identity and its behavioral preference are represented in the population activity of the projection neurons. Our results provide the first detailed description of olfactory neurons in the central nervous system of mosquitoes and lay a foundation for understanding the neural basis of their olfactory behaviors.