bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety Outcomes of Mechanical Thrombectomy Versus Combined Thrombectomy and Intravenous Thrombolysis in Tandem Lesions
Authors: Rodriguez-Calienes Aaron , Galecio-Castillo Milagros , Farooqui Mudassir , Hassan Ameer E. , Jumaa Mouhammad A. , Divani Afshin A. , Ribo Marc , Abraham Michael , Petersen Nils H. , Fifi Johanna , Guerrero Waldo R. , Malik Amer M. , Siegler James E. , Nguyen Thanh N. , Yoo Albert J. , Linares Guillermo , Janjua Nazli , Quispe-Orozco Darko , Tekle Wondwossen G. , Alhajala Hisham , Ikram Asad , Rizzo Federica , Qureshi Abid , Begunova Liza , Matsouka Stavros , Vigilante Nicholas , Salazar-Marioni Sergio , Abdalkader Mohamad , Gordon Weston , Soomro Jazba , Turabova Charoskon , Vivanco-Suarez Juan , Mokin Maxim , Yavagal Dileep R. , Jovin Tudor , Sheth Sunil , Ortega-Gutierrez Santiago 
Published: February 2023

ABSTRACTBackground and PurposeWe aimed to describe the safety and efficacy of mechanical thrombectomy (MT) with or without intravenous thrombolysis (IVT) for patients with tandem lesions (TLs) and whether using intraprocedural antiplatelet therapy (APT) influences MT’s safety with IVT treatment.MethodsThis is a sub-analysis of a pooled, international multicenter cohort of patients with acute anterior circulation TLs treated with MT. Primary outcomes included symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2 (PH2). Additional outcomes included hemorrhagic transformation (HT), successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] 2b-3), complete reperfusion (mTICI 3), favorable functional outcome (90-day modified Rankin score [mRS] 0-2), excellent functional outcome (90-day mRS 0-1), in-hospital mortality, and 90-days mortality.ResultsOf 691 patients, 599 were included (255 underwent IVT+MT and 344 MT alone). There was no difference in the risk of sICH (aOR=1.43; 95%CI:0.72–2.87;p=0.308), PH2 (aOR=1.14; 95%CI:0.57– 2.28;p=0.705), and HT (aOR=0.92; 95%CI:0.54–1.57;p=0.751) between the IVT+MT and MT alone groups after adjusting for confounders. There was an IVT-by-intraprocedural APT interaction for sICH (pinteraction=0.031). Administration of IVT was associated with an increased risk of sICH in patients who received IV-APT (aOR=3.58; 95%CI:1.17–10.89;p=0.025). The IVT+MT group had higher odds of 90-days mRS 0-2 (aOR=1.76; 95%CI:1.05–2.94;p=0.030). The odds of successful reperfusion, complete reperfusion, 90-days mRS 0-1, in-hospital mortality, or 90-days mortality did not differ between the IVT+MT vs. MT alone groups.ConclusionOur study showed that the combination of IVT with MT for TL did not increase the overall risk of sICH, PH2, or overall HT independently of the cervical revascularization technique used. However, intraprocedural IV-ATP during acute stent implantation might be associated with an increased risk of sICH in patients who received IVT prior to MT. Importantly, IVT+MT treatment was associated with a higher rate of favorable functional outcome at 90 days.
Machine learning-assisted medium optimization revealed the discriminated strategies for improved production of the foreign and native metabolites
Authors: Aida Honoka , Uchida Keisuke , Nagai Motoki , Hashizume Takamasa , Masuo Shunsuke , Takaya Naoki , Ying Bei-Wen 
Published: February 2023

AbstractThe medium composition was crucial for achieving the best performance of synthetic construction. What and how medium components determined the production of the synthetic construction remained poorly investigated. To address the questions, a comparative survey with two genetically engineeredEscherichia colistrains was performed. As a case study, the strains carried the synthetic pathways for producing the aromatic compounds of 4APhe or Tyr, which were common in the upstream but differentiated in the downstream metabolism. Bacterial growth and compound production were examined in hundreds of medium combinations that comprised 48 pure chemicals. The resultant data sets linking the medium composition to bacterial growth and production were subjected to machine learning for improved production. Intriguingly, the primary medium components determining the production of 4PheA and Tyr were differentiated, which were the initial resource (glucose) of the synthetic pathway and the inducer (IPTG) of the synthetic construction, respectively. Fine-tuning of the primary component significantly increased the yields of 4APhe and Tyr, indicating that a single component could be crucial for the performance of synthetic construction. Transcriptome analysis observed the local and global changes in gene expression for improved production of 4APhe and Tyr, respectively, revealing divergent metabolic strategies for producing the foreign and native metabolites. The study demonstrated that ML-assisted medium optimization could provide a novel point of view on how to make the synthetic construction meet the original design.
Transposon accumulation at xenobiotic gene family loci: a comparative genomic analysis in aphids
Authors: Baril Tobias , Pym Adam , Bass Chris , Hayward Alex 
Published: February 2023

AbstractThe evolution of resistance is a major challenge for the sustainable control of pests and pathogens. Thus, a deeper understanding of the evolutionary and genomic mechanisms underpinning resistance evolution is required to safeguard health and food production. Several studies have implicated transposable elements (TEs) in xenobiotic resistance evolution in insects. However, analyses are generally restricted to one insect species and/or one or a few xenobiotic gene families (XGFs). We examine evidence for TE accumulation at XGFs by performing a comparative genomic analysis across 20 aphid genomes, considering major subsets of XGFs involved in metabolic resistance to insecticides: Cytochrome P450s, glutathione S-transferases, esterases, UDP-glucuronosyltransferases, and ABC transporters. We find that TEs are significantly enriched at XGFs compared to other genes. XGFs show similar levels of TE enrichment to housekeeping genes. But unlike housekeeping genes, XGFs are not constitutively expressed in germline cells, supporting the selective enrichment of TEs at XGFs, rather than enrichment due to chromatin availability. Hotspots of extreme TE enrichment occur around certain XGFs. In aphids of agricultural importance, we find particular enrichment of TEs around cytochrome P450 genes with known functions in the detoxification of synthetic insecticides. Our results provide evidence supporting a general role for TEs as a source of genomic variation at host XGFs, and highlight the existence of considerable variability in TE content across XGFs and host species. These findings demonstrate the need for detailed functional verification analyses to clarify the significance of individual TE insertions and elucidate underlying mechanisms at TE-XGF hotspots.
Biophysical characterization and modeling ofSCN1Again-of-function predicts interneuron hyperexcitability and a predisposition to network instability through homeostatic plasticity
Authors: Berecki Géza , Bryson Alexander , Polster Tilman , Petrou Steven 
Published: February 2023

ABSTRACTSCN1Again-of-function variants are associated with early onset developmental and epileptic encephalopathies (DEEs) that possess distinct clinical features compared to Dravet syndrome caused bySCN1Aloss-of-function. However, it is unclear howSCN1Again-of-function may predispose to cortical hyper-excitability and seizures. Here, we first report the clinical features of a patient carrying ade novo SCN1Avariant (T162I) associated with neonatal-onset DEE, and then characterize the biophysical properties of T162I and three otherSCN1Avariants associated with neonatal-onset or early infantile DEE (I236V, P1345S, R1636Q). In voltage clamp experiments, three variants (T162I, P1345S and R1636Q) exhibited changes in activation and inactivation properties that enhanced window current, consistent with gain-of-function. Dynamic action potential clamp experiments utilising model neurons incorporating Nav1.1. channels supported a gain-of-function mechanism for all four variants. Here, the T162I, I236V, P1345S, and R1636Q variants exhibited higher peak firing rates relative to wild type and the T162I and R1636Q variants produced a hyperpolarized threshold and reduced neuronal rheobase. To explore the impact of these variants upon cortical excitability, we used a spiking network model containing an excitatory pyramidal cell (PC) and parvalbumin positive (PV) interneuron population.SCN1Again-of-function was modeled by enhancing the excitability of PV interneurons and then incorporating three simple forms of homeostatic plasticity that restored pyramidal cell firing rates. We found that homeostatic plasticity mechanisms exerted differential impact upon network function, with changes to PV- to-PC and PC-to-PC synaptic strength predisposing to network instability. Overall, our findings support a role forSCN1Again-of-function and inhibitory interneuron hyperexcitability in early onset DEE. We propose a mechanism through which homeostatic plasticity pathways can predispose to pathological excitatory activity and contribute to phenotypic variability inSCN1Adisorders.
OPTIMAL: An OPTimised Imaging Mass cytometry AnaLysis framework for benchmarking segmentation and data exploration
Authors: Hunter Bethany , Nicorescu Ioana , Foster Emma , McDonald David , Hulme Gillian , Fuller Andrew , Thomson Amanda , Goldsborough Thibaut , Hilkens Catharien M.U. , Majo Joaquim , Milross Luke , Fisher Andrew , Bankhead Peter , Wills John , Rees Paul , Filby Andrew , Merces George 
Published: February 2023

AbstractAnalysis of Imaging Mass Cytometry (IMC) data and other low-resolution multiplexed tissue imaging technologies is often confounded by poor single cell segmentation and sub-optimal approaches for data visualisation and exploration. This can lead to inaccurate identification of cell phenotypes, states or spatial relationships compared to reference data from single cell suspension technologies. To this end we have developed the “OPTIMAL” framework to benchmark any approaches for cell segmentation, parameter transformation, batch effect correction, data visualisation/clustering and spatial neighbourhood analysis. Using a panel of 27 metal-tagged antibodies recognising well characterised phenotypic and functional markers to stain the same FFPE human tonsil sample Tissue Microarray (TMA) over 12 temporally distinct batches we tested several cell segmentation models, a range of differentarcsinhcofactor parameter transformation values, five different dimensionality reduction algorithms and two clustering methods. Finally we assessed the optimal approach for performing neighbourhood analysis. We found that single cell segmentation was improved by the use of an Ilastik-derived probability map but that issues with poor segmentation were only really evident after clustering and cell type/state identification and not always evident when using “classical” bi-variate data display techniques. The optimalarcsinhcofactor for parameter transformation was 1 as it maximised the statistical separation between negative and positive signal distributions and a simple Z-score normalisation step afterarcsinhtransformation eliminated batch effects. Of the five different dimensionality reduction approaches tested, PacMap gave the best data structure with FLOWSOM clustering out-performing Phenograph in terms of cell type identification. We also found that neighbourhood analysis was influenced by the method used for finding neighbouring cells with a “disc” pixel expansion outperforming a “bounding box” approach combined with the need for filtering objects based on size and image-edge location. Importantly OPTIMAL can be used to assess and integrate with any existing approach to IMC data analysis and, as it creates .FCS files from the segmentation output, allows for single cell exploration to be conducted using a wide variety of accessible software and algorithms familiar to conventional flow cytometrists.
Markerless motion capture estimates of lower extremity kinematics and kinetics are comparable to marker-based across 8 movements
Authors: Song Ke , Hullfish Todd J. , Silva Rodrigo Scattone , Silbernagel Karin Grävare , Baxter Josh R. 
Published: February 2023

ABSTRACTMotion analysis is essential for assessing in-vivo human biomechanics. Marker-based motion capture is the standard to analyze human motion, but the inherent inaccuracy and practical challenges limit its utility in large-scale and real-world applications. Markerless motion capture has shown promise to overcome these practical barriers. However, its fidelity in quantifying joint kinematics and kinetics has not been verified across multiple common human movements. In this study, we concurrently captured marker-based and markerless motion data on 10 healthy subjects performing 8 daily living and exercise movements. We calculated the correlation (Rxy) and root-mean-square difference (RMSD) between markerless and marker-based estimates of ankle dorsi-plantarflexion, knee flexion, and three-dimensional hip kinematics (angles) and kinetics (moments) during each movement. Estimates from markerless motion capture matched closely with marker-based in ankle and knee joint angles (Rxy≥ 0.877, RMSD ≤ 5.9°) and moments (Rxy≥ 0.934, RMSD ≤ 2.66 % height × weight). High outcome comparability means the practical benefits of markerless motion capture can simplify experiments and facilitate large-scale analyses. Hip angles and moments demonstrated more differences between the two systems (RMSD: 6.7° – 15.9° and up to 7.15 % height × weight), especially during rapid movements such as running. Markerless motion capture appears to improve the accuracy of hip-related measures, yet more research is needed for validation. We encourage the biomechanics community to continue verifying, validating, and establishing best practices for markerless motion capture, which holds exciting potential to advance collaborative biomechanical research and expand real-world assessments needed for clinical translation.
Ubiquinone deficiency drives reverse electron transport to disrupt hepatic metabolic homeostasis in obesity
Authors: Goncalves Renata L.S. , Wang Zeqiu Branden , Inouye Karen E. , Lee Grace Yankun , Fu Xiaorong , Saksi Jani , Rosique Clement , Parlakgul Gunes , Arruda Ana Paula , Hui Sheng Tony , Loperena Mar Coll , Burgess Shawn C. , Graupera Isabel , Hotamisligil Gökhan S. 
Published: February 2023

AbstractMitochondrial reactive oxygen species (mROS) are central to physiology. While excess mROS production has been associated with several disease states, its precise sources, regulation, and mechanism of generationin vivoremain unknown, limiting translational efforts. Here we show that in obesity, hepatic ubiquinone (Q) synthesis is impaired, which raises the QH2/Q ratio, driving excessive mROS production via reverse electron transport (RET) from site IQin complex I. Using multiple complementary genetic and pharmacological modelsin vivowe demonstrated that RET is critical for metabolic health. In patients with steatosis, the hepatic Q biosynthetic program is also suppressed, and the QH2/Q ratio positively correlates with disease severity. Our data identify a highly selective mechanism for pathological mROS production in obesity, which can be targeted to protect metabolic homeostasis.
Evolutionary changes in germ granule mRNA content are driven by multiple mechanisms inDrosophila
Authors: Doyle Dominique A. , Burian Florencia N. , Aharoni Benjamin , Klinder Annabelle J. , Menzel Melissa M. , Nifras Gerard Carlo C. , Shabazz-Henry Ahad L. , Palma Bianca Ulrich , Hidalgo Gisselle A. , Sottolano Christopher J. , Ortega Bianca M. , Niepielko Matthew G. 
Published: February 2023

AbstractThe co-packaging of mRNAs into biomolecular condensates called germ granules is a conserved strategy to post-transcriptionally regulate mRNAs that function in germline development and maintenance. InD. melanogaster, mRNAs accumulate in germ granules by forming homotypic clusters, aggregates that contain multiple transcripts from a specific gene. Nucleated by Oskar (Osk), homotypic clusters inD. melanogasterare generated through a stochastic seeding and self-recruitment process that requires the 3’ UTR of germ granule mRNAs. Interestingly, the 3’ UTR belonging to germ granule mRNAs, such asnanos(nos), have considerable sequence variations amongDrosophilaspecies. Thus, we hypothesized that evolutionary changes in the 3’ UTR influences germ granule development. To test our hypothesis, we investigated the homotypic clustering ofnosandpolar granule component(pgc) in fourDrosophilaspecies and concluded that homotypic clustering is a conserved developmental process used to enrich germ granule mRNAs. Additionally, we discovered that the number of transcripts found innosand/orpgcclusters could vary significantly among species. By integrating biological data with computational modeling, we determined that multiple mechanisms underlie naturally occurring germ granule diversity, including changes innos,pgc,osklevels, and/or homotypic clustering efficacy. Finally, we found that thenos3’ UTR from different species can alter the efficacy ofnoshomotypic clustering, resulting in germ granules with reducednosaccumulation. Our findings highlight the impact that evolution has on the development of germ granules and may provide insight into processes that modify the content of other classes of biomolecular condensates.
Signalling-dependent refinement of cell fate choice during tissue remodelling
Authors: Herszterg Sophie , de Gennes Marc , Cicolini Simone , Huang Anqi , Alexandre Cyrille , Smith Matthew , Araujo Helena , Vincent Jean-Paul , Salbreux Guillaume 
Published: February 2023

SUMMARYHow biological form emerges from cell fate decisions and tissue remodelling is a fundamental question in development biology. However, an understanding of how these processes operate side-by-side to set precise and robust patterns is largely missing. Here, we investigate this interplay during the process of vein refinement in theDrosophilapupal wing. By following reporters of signalling activity dynamically, together with tissue flows, we show that longitudinal vein refinement arises from a combination of local tissue deformation and cell fate adjustments controlled by a signalling network involving Notch, Dpp, and EGFR. Perturbing large-scale convergence and extension tissue flows does not affect vein refinement, showing that pre-patterned vein domains are able to intrinsically refine to the correct width. A minimal biophysical description taking into account key signalling interactions recapitulates the intrinsic tissue ability to establish a thin, regular vein independently of large-scale tissue flows. Supporting this prediction, artificial proveins optogenetically generated orthogonal to the axis of wing elongation refine against large-scale flows. Overall, we find that signalling-mediated updating of cell fate is a key contributor to reproducible patterning.
The use of DNA barcoding for the identification of giant hogweeds in the European North-East of Russia
Authors: Shadrin D.M. , Dalke I.V. , Zakhozhiy I.G. , Shilnikov D.S. , Kozhin M.N. , Chadin I.F. 
Published: February 2023

AbstractQualitative differences in the nrDNA ITS and ETS sequences in the total sample were determined to allow identification of the following groups of samples:H. mantegazzianum, H. cf.sosnowskyi, H. cf.mantegazzianumandH. cf.sosnowskyi×H. cf.mantegazzianumamong other representatives of theHeracleumgenus presented in the genetic databases. The study revealed the absence of correlation between a sample type in the groupH. mantegazzianum, H. cf.sosnowskyi, H. cf.mantegazzianumandH. cf.sosnowskyi×H. cf.mantegazzianumand qualitative transformations in the ITS and ETS sequences. The qualitative analysis of the rbcL, matK, rps16 intron, intergenic spacers psbA-trnH, trnQ-rps16, rps16-trnK and rpl32-trnL cpDNA sequences for the samples identified asHeracleum mantegazzianum,H. cf.sosnowskyi,H. cf.mantegazzianumandH. cf.sosnowskyi×H. cf.mantegazzianumdemonstrated no correlation between them as well.
Interferon inhibits a model RNA virus via a limited set of inducible effector genes
Authors: McDougal Matthew B. , De Maria Anthony M. , Ohlson Maikke B. , Kumar Ashwani , Xing Chao , Schoggins John W. 
Published: February 2023

AbstractInterferons control viral infection by inducing the expression of antiviral effector proteins encoded by interferon-stimulated genes (ISGs). The field has mostly focused on identifying individual antiviral ISG effectors and defining their mechanisms of action. However, fundamental gaps in knowledge about the interferon response remain. For example, it is not known how many ISGs are required to protect cells from a particular virus, though it is theorized that numerous ISGs act in concert to achieve viral inhibition. Here, we used CRISPR-based loss-of-function screens to identify a markedly limited set of ISGs that confer interferon-mediated suppression of a model alphavirus, Venezuelan equine encephalitis virus (VEEV). We show via combinatorial gene targeting that three antiviral effectors – ZAP, IFIT3, and IFIT1 – together constitute the majority of interferon-mediated restriction of VEEV, while accounting for less than 0.5% of the interferon-induced transcriptome. Together, our data suggests a refined model of the antiviral interferon response in which a small subset of “dominant” ISGs may confer the bulk of the inhibition of a given virus.