bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heparin-derived theranostic nanoprobes overcome the blood brain barrier and target glioma in murine model
Authors: Samanta Sumanta , Joncour Vadim Le , Wegrzyniak Olivia , Rangasami Vignesh Kumar , Ali-Löytty Harri , Hong Taehun , Selvaraju Ram Kumar , Aberg Ola , Hilborn Jons , Laakkonen Pirjo , Varghese Oommen P. , Eriksson Olof , Cabral Horacio , Oommen Oommen P. 
Published: January 2022

ABSTRACTThe poor permeability of theranostic agents across the blood-brain-barrier (BBB) significantly hampers the development of new treatment modalities for neurological diseases. We have discovered a new biomimetic nanocarrier using heparin (HP) that effectively passes the BBB and targets glioblastoma. Specifically, we designed HP coated gold nanoparticles (HP-AuNPs) that were labeled with three different imaging modalities namely, fluorescein (FITC-HP-AuNP), radioisotope 68Gallium (68Ga-HP-AuNPs), and MRI active gadolinium (Gd-HP-AuNPs). The systemic infusion of FITC-HP-AuNPs in three different mouse strains (C57BL/6JRj, FVB, and NMRI-nude) displayed excellent penetration and revealed uniform distribution of fluorescent particles in the brain parenchyma (69-86%) with some accumulation in neurons (8-18%) and microglia (4-10%). Tail-vein administration of radiolabeled 68Ga-HP-AuNPs in healthy rats also showed 68Ga-HP-AuNP inside the brain parenchyma and in areas containing cerebrospinal fluid, such as the lateral ventricles, the cerebellum, and brain stem. Finally, tail-vein administration of Gd-HP-AuNPs (that display ∼3 fold higher relaxivity than that of commercial Gd-DTPA) in an orthotopic glioblastoma (U87MG xenograft) model in nude mice demonstrated enrichment of T1-contrast at the intracranial tumor with a gradual increase in the contrast in the tumor region between 1h-3h. We believe, our finding offers the untapped potential of HP-derived-NPs to deliver cargo molecules for treating neurological disorders.
Chaining for Accurate Alignment of Erroneous Long Reads to Acyclic Variation Graphs*
Authors: Ma Jun , Cáceres Manuel , Salmela Leena , Mäkinen Veli , Tomescu Alexandru I. 
Published: January 2022

AbstractAligning reads to a variation graph is a standard task in pangenomics, with downstream applications such as improving variant calling. While thevgtoolkit (Garrison et al.,Nature Biotechnology, 2018) is a popular aligner of short reads,GraphAligner(Rautiainen and Marschall,Genome Biology, 2020) is the state-of-the-art aligner of erroneous long reads.GraphAlignerworks by finding candidate read occurrences based onindividuallyextending the best seeds of the read in the variation graph. However, a more principled approach recognized in the community is to co-linearly chainmultipleseeds.We present a new algorithm to co-linearly chain a set of seeds in a string labeled acyclic graph, together with the first efficient implementation of such a co-linear chaining algorithm into a new aligner of erroneous long reads to acyclic variation graphs,GraphChainer. Compared toGraphAligner,GraphChaineraligns 12% to 17% more reads, and 21% to 28% more total read length, on real PacBio reads from human chromosomes 1, 22 and the whole human pangenome. On both simulated and real data,GraphChaineraligns between 95% and 99% of all reads, and of total read length. We also show thatminigraph(Li et al.,Genome Biology, 2020) andminichain(Chandra and Jain,RECOMB, 2023) obtain an accuracy of less than 60% on this setting.GraphChaineris freely available athttps://github.com/algbio/GraphChainer. The datasets and evaluation pipeline can be reached from the previous address.
In vitro and in vivo venom-inhibition assays identify metalloproteinase-inhibiting drugs as potential treatments for snakebite envenoming by Dispholidus typus
Authors: Menzies Stefanie K. , Clare Rachel H. , Xie Chunfang , Westhorpe Adam , Hall Steven R. , Edge Rebecca J. , Alsolaiss Jaffer , Crittenden Edouard , Harrison Robert A , Kool Jeroen , Casewell Nicholas R. 
Published: January 2022

AbstractSnakebite envenoming affects more than 250,000 people annually in sub-Saharan Africa. Envenoming by Dispholidus typus (boomslang) results in venom induced consumption coagulopathy, whereby highly abundant prothrombin-activating snake venom metalloproteinases (SVMPs) consume clotting factors and deplete fibrinogen. The only available treatment for D. typus envenoming is the monovalent SAIMR Boomslang antivenom. Treatment options are urgently required because this antivenom is often difficult to source and, at $6,000/vial, typically unaffordable for most snakebite patients. We therefore investigated the in vitro and in vivo preclinical efficacy of four SVMP inhibitors to neutralise the effects of D. typus venom; the matrix metalloproteinase inhibitors marimastat and prinomastat, and the metal chelators dimercaprol and DMPS. The venom of D. typus exhibited an SVMP-driven procoagulant phenotype in vitro. Marimastat and prinomastat demonstrated equipotent inhibition of the SVMP-mediated procoagulant activity of the venom in vitro, whereas dimercaprol and DMPS showed considerably lower potency. However, when tested in preclinical murine models of envenomation, DMPS and marimastat demonstrated partial protection against venom lethality, demonstrated by prolonged survival times of experimental animals, whereas dimercaprol and prinomastat failed to confer any protection at the doses tested. The results presented here demonstrate that DMPS and marimastat show potential as novel small molecule-based therapeutics for D. typus snakebite envenomation. These two drugs have been previously shown to be effective against Echis ocellatus venom induced consumption coagulopathy (VICC) in preclinical models, and thus we conclude that marimastat and DMPS may be valuable early intervention therapeutics to broadly treat VICC following snakebite envenoming in sub-Saharan Africa.
Wnt/PCP signaling mediates breast cancer metastasis by promoting pro-invasive protrusion formation in collectively motile leader cells
Authors: VanderVorst Kacey , Dreyer Courtney A. , Hatakeyama Jason , Bell George R. R. , Berg Anastasia L. , Hernandez Maria , Lee Hyun , Collins Sean R. , Carraway Kermit L. 
Published: January 2022

AbstractAs evidence supporting essential roles for collective cell migration in carcinoma metastasis continues to accumulate, a better understanding of the underlying cellular and molecular mechanisms will be critical to translating these findings to the treatment of advanced cancers. Here we report that Wnt/PCP, a non-canonical Wnt signaling pathway, mediates breast cancer collective migration and metastasis. We observe that mammary gland-specific knockout of Vangl2, a tetraspanin-like scaffolding protein required for Wnt5a-induced signaling and motility in cultured breast cancer cell lines, results in a striking decrease in metastatic efficiency but not primary tumor growth in the MMTV-NDL transgenic mouse model of HER2-positive breast cancer. We also observe that expression levels of core Wnt/PCP components Wnt5a, Vangl1 and Vangl2 are selectively elevated in K14-positive leader cells relative to follower cells within a collectively migrating cohort, and that Vangl2 expression selectively promotes RhoA activation in leading edge cells. Moreover, Vangl expression drives collective migration in three-dimensional ex vivo tumor organoids, and Vangl protein specifically accumulates within pro-migratory filamentous actin-rich protrusions of leader cells. Together, our observations point to a model whereby Wnt/PCP upregulation facilitates breast tumor collective cell motility by selectively augmenting the formation pro-migratory protrusions within leader cells.
Differences in pathways contributing to thyroid hormone effects on postnatal cartilage calcification versus secondary ossification center development
Authors: Gomez Gustavo A. , Aghajanian Patrick , Pourteymoor Sheila , Larkin Destiney , Mohan Subburaman 
Published: January 2022

AbstractThe proximal and distal femur epiphysis of mice are both weight bearing structures derived from chondrocytes but differ in development. Mineralization at the distal epiphysis occurs in an osteoblast rich secondary ossification center (SOC), while the chondrocytes of the proximal femur head (FH) in particular, are directly mineralized. Thyroid hormone (TH) plays important roles in distal knee SOC formation, but whether TH also affects proximal FH development remains unexplored. Here, we found that TH controls chondrocyte maturation and mineralization at the FH in vivo through studies in Thyroid stimulating hormone receptor (Tshr-/-) hypothyroid mice by X-ray, histology, transcriptional profiling, and immunofluorescence staining. Both in vivo, and in vitro studies conducted in ATDC5 chondrocyte progenitors concur that TH regulates expression of genes that modulate mineralization (Bsp, Ocn, Dmp1, Opn, and Alp). Our work also delineates differences in prominent transcription factor regulation of genes involved in the different mechanisms leading to proximal FH cartilage calcification and endochondral ossification at the distal femur. The information on the molecular pathways contributing to postnatal cartilage calcification can provide insights on therapeutic strategies to treat pathological calcification that occurs in soft tissues such as aorta, kidney, and articular cartilage.
Busy and confused? High risk of missed alerts in the cockpit: an electrophysiological study
Authors: Causse Mickael , Parmentier Fabrice B. R. , Mouratille Damien , Thibaut Dorothée , Kisselenko Marie , Fabre Eve 
Published: January 2022

AbstractOf evolutionary importance, the ability to react to unexpected auditory stimuli remains critical today, especially in settings such as aircraft cockpits or air traffic control towers, characterized by high mental and auditory loads. Evidences show that both factors can negatively impact auditory attention and prevent appropriate reactions in hazardous situations. In the present study, sixty participants performed a simulated aviation task, varying in terms of mental load (no, low, high mental load), that was embedded with a concurrent tone detection paradigm, in which auditory load was manipulated by the number of different tones (1, 2 or 3). We measured both detection performance (miss, false alarm) and brain activity (event-related potentials) related to the target tone. Our results showed that both mental and auditory loads affected tone detection performance. Importantly, their combined effects had a massive impact on the percentage of missed target tones. While, in the no mental load condition, miss rate was very low with 1 (0.53%) and 2 tones (1.11%), it increased drastically with 3 tones (24.44%), and this effect was accentuated as mental load increased, yielding to the higher miss rate in the 3-tone paradigm under high mental load conditions (68.64%). Increased mental load, auditory load, and miss rate, were all associated with disrupted brain response to the target tone as showed by reductions of the P3b amplitude. In sum, our results highlight the importance of balancing mental and auditory loads to maintain or improve efficient reactions to alarms in complex environment.
Integrating Cell Morphology with Gene Expression and Chemical Structure to Aid Mitochondrial Toxicity Detection
Authors: Seal Srijit , Carreras-Puigvert Jordi , Trapotsi Maria-Anna , Yang Hongbin , Spjuth Ola , Bender Andreas 
Published: January 2022

ABSTRACTMitochondrial toxicity is an important safety endpoint in drug discovery. Models based solely on chemical structure for predicting mitochondrial toxicity are currently limited in accuracy and applicability domain to the chemical space of the training compounds. In this work, we aimed to utilize both -omics and chemical data to push beyond the state-of-the-art. We combined Cell Painting and Gene Expression data with chemical structural information from Morgan fingerprints for 382 chemical perturbants tested in the Tox21 mitochondrial membrane depolarization assay. We observed that mitochondrial toxicants differ from non-toxic compounds in morphological space and identified compound clusters having similar mechanisms of mitochondrial toxicity, thereby indicating that morphological space provides biological insights related to mechanisms of action of this endpoint. We further showed that models combining Cell Painting, Gene Expression features and Morgan fingerprints improved model performance on an external test set of 244 compounds by 60% (in terms of F1 score) and improved extrapolation to new chemical space. The performance of our combined models was comparable with dedicated in vitro assays for mitochondrial toxicity. Our results suggest that combining chemical descriptors with biological readouts enhances the detection of mitochondrial toxicants, with practical implications in drug discovery.Abstract FigureGraphical Abstract
Comparing transmission reconstruction models with Mycobacterium tuberculosis whole genome sequence data
Authors: Sobkowiak Benjamin , Romanowski Kamila , Sekirov Inna , Gardy Jennifer L , Johnston James 
Published: January 2022

AbstractPathogen genomic epidemiology is now routinely used worldwide to interrogate infectious disease dynamics. Multiple computational tools that reconstruct transmission networks by coupling genomic data with epidemiological modelling have been developed. The resulting inferences are often used to inform outbreak investigations, yet to date, the performance of these transmission reconstruction tools has not been compared specifically for tuberculosis, a disease process with complex epidemiology that includes variable latency periods and within-host heterogeneity. Here, we carried out a systematic comparison of seven publicly available transmission reconstruction tools, evaluating their accuracy in predicting transmission events in both simulated and real-world Mycobacterium tuberculosis outbreaks. No tool was able to fully resolve transmission networks, though both the single-tree and multi-tree input implementations of TransPhylo identified the most epidemiologically supported transmission events and the fewest false positive links. We observed a high degree of variability in the transmission networks inferred by each approach. Our findings may inform an end-user’s choice of tools in future tuberculosis transmission analyses and underscore the need for caution when interpreting transmission networks produced using probabilistic approaches.
Raman Signal Denoising using Fully Convolutional Encoder Decoder Network
Authors: Loc Irem , Kecoglu Ibrahim , Unlu Mehmet Burcin , Parlatan Ugur 
Published: January 2022

AbstractRaman spectroscopy is a vibrational method that gives molecular information rapidly and non-invasively. Despite its advantages, the weak intensity of Raman spectroscopy leads to low-quality signals, particularly with tissue samples. The requirement of high exposure times makes Raman a time-consuming process and diminishes its non-invasive property while studying living tissues. Novel denoising techniques using convolutional neural networks (CNN) have achieved remarkable results in image processing. Here, we propose a similar approach for noise reduction for the Raman spectra acquired with 10x lower exposure times. In this work, we developed fully convolutional encoder-decoder architecture (FCED) and trained them with noisy Raman signals. The results demonstrate that our model is superior (p-value < 0.0001) to the conventional denoising techniques such as the Savitzky-Golay filter and wavelet denoising. Improvement in the signal-to-noise ratio values ranges from 20% to 80%, depending on the initial signal-to-noise ratio. Thus, we proved that tissue analysis could be done in a shorter time without any need for instrumental enhancement.
Delayed processing of blood samples impairs the accuracy of mRNA-based biomarkers
Authors: Wilson Chace , Dias Nicolas W. , Pancini Stefania , Mercadante Vitor , Biase Fernando H. 
Published: January 2022

ABSTRACTBackgroundThe transcriptome of peripheral white blood cells (PWBCs) contains valuable physiological information, thus making them a prime biological sample for investigating mRNA-based biomarkers. However, prolonged storage of whole blood samples can alter gene transcript abundance in PWBCs, compromising the results of biomarker discovery. Here, we designed an experiment to interrogate the impacts of delayed processing of whole blood samples on gene transcript abundance in PWBCs. We hypothesized that storing blood samples for 24 hours at 4°C would cause RNA degradation resulting in altered transcriptome profiles.ResultsWe produced RNA-sequencing data for 30 samples collected from five estrus synchronized heifers (Bos taurus). We quantified transcript abundance for 12,414 protein-coding genes in PWBCs. Analysis of parameters of RNA quality revealed no statistically significant differences (P>0.05) between samples collected from the jugular vein and coccygeal vein, as well as among samples processed after one, three, six, or eight hours. However, samples processed after 24 hours of storage had a lower RNA integrity number value (P=0.03) in comparison to those processed after one hour of storage. Next, we analyzed RNA-sequencing data between samples using those processed after one hour of storage as the baseline for comparison. Interestingly, evaluation of 3’/5’ bias revealed no differences between genes with lower transcript abundance in samples stored for 24 hours relative to one hour. In addition, sequencing coverage of transcripts was similar between samples from the 24-hour and one-hour groups. We identified four and 515 genes with differential transcript abundance in samples processed after storage for eight and 24 hours, respectively, relative to samples processed after one hour.ConclusionsThe PWBCs respond to prolonged cold storage by increasing genes related to active chromatin compaction which in turn reduces gene transcription. This alteration in transcriptome profiles can impair the accuracy of mRNA-based biomarkers. Therefore, blood samples collected for mRNA-based biomarker discovery should be refrigerated immediately and processed within six hours post sampling.
Regulation of Chromatin Accessibility by hypoxia and HIF
Authors: Batie Michael , Frost Julianty , Shakir Dilem , Rocha Sonia 
Published: January 2022

AbstractReduced oxygen availability (hypoxia) can act as a signalling cue in physiological processes such as development, but also in pathological conditions such as cancer or ischaemic disease. As such, understanding how cells and organisms respond to hypoxia is of great importance. The family of transcription factors called Hypoxia Inducible Factors (HIFs) coordinate a transcriptional programme required for survival and adaptation to hypoxia. The effects of hypoxia and HIF on the chromatin accessibility landscape are still unclear. Here, using genome wide mapping of chromatin accessibility via ATAC-seq, we find hypoxia induces loci specific changes in chromatin accessibility enriched at hypoxia transcriptionally responsive genes. These changes are predominantly HIF dependent, reversible upon reoxygenation and partially mimicked by chemical HIF stabilisation independent of molecular dioxygenase inhibition. This work demonstrates that indeed, HIF stabilisation is necessary and sufficient to alter chromatin accessibility in hypoxia, with implications for our understanding of gene expression regulation by hypoxia and HIF.
Corrosion behavior of 2205 duplex stainless steel in acidizing stimulation solution for oil and gas wells at 200°C
Authors: Du Juan , Yu Mengyao , Liu Pingli , Fu Yongqiang , Xiong Gang , Liu Jinming , Chen Xiang 
Published: January 2022

Purpose
This paper aims to analyze the high temperature (200°C) corrosion behavior of 2205 duplex stainless steel in acidizing stimulation solution containing hydrochloric acid (HCl) and acetic acid.

Design/methodology/approach
The corrosion rate of 2205 duplex stainless steel in all kinds of acid solutions was calculated through immersion tests and electrochemical test. The corrosion product composition is analyzed by X-ray diffraction analysis. The element composition and element distribution before and after corrosion were analyzed by an X-ray energy spectrometer. The corrosion morphology of the steel surface was observed by a scanning electron microscope. Both static and dynamic corrosion experiments were carried out at 200°C.

Findings
The results show that 2205 duplex stainless steel has excellent corrosion resistance in low to high concentration acetic acid solutions, but increasing the concentration of Cl− in acetic acid solution will accelerate the corrosion rate. Low concentration HCl solution can cause serious corrosion to 2205 duplex stainless steel. The system of HCl and acetic acid will produce a synergistic effect on corrosion of 2205 duplex stainless steel and accelerate the corrosion. Sb2O3 is a good corrosion inhibitor synergist for high-temperature acidizing stimulation solution.

Originality/value
The amount of HCl that is used in acidizing stimulation is usually determined by the dissolution effect of the acid on the rocks, but for ultra-high-temperature reservoirs, the amount of HCl should be based on reducing the corrosion of oil and gas wells.
Review on critical technology development of avian radar system
Authors: Chen Weishi , Huang Yifeng , Lu Xianfeng , Zhang Jie 
Published: January 2022

Purpose
This paper aims to review the critical technology development of avian radar system at airports.

Design/methodology/approach
After the origin of avian radar technology is discussed, the target characteristics of flying birds are analyzed, including the target echo amplitude, flight speed, flight height, trajectory and micro-Doppler. Four typical airport avian radar systems of Merlin, Accipiter, Robin and CAST are introduced. The performance of different modules such as antenna, target detection and tracking, target recognition and classification, analysis of bird information together determines the detection ability of avian radar. The performances and key technologies of the ubiquitous avian radar are summarized and compared with other systems, and their applications, deployment modes, as well as their advantages and disadvantages are introduced and analyzed.

Findings
The ubiquitous avian radar achieves the long-time integration of target echoes, which greatly improves detection and classification ability of the targets of birds or drones, even under strong background clutter at airport. In addition, based on the big data of bird situation accumulated by avian radar, the rules of bird activity around the airport can be mined to guide the bird avoidance work.

Originality/value
This paper presented a novel avian radar system based on ubiquitous digital radar technology. The authors’ experience has confirmed that this system can be effective for airport bird strike prevention and management. In the future, the avian radar system will see continued improvement in both software and hardware, as the system is designed to be easily extensible.