Functional mitochondria are critically important for the maintenance of cellular integrity and survival. Mitochondrial dysfunction is a major contributor to neurodegenerative diseases including ...Parkinson's disease (PD). Two gene products mutated in familial Parkinsonism, PINK1 and Parkin, function together to degrade damaged mitochondria through a selective form of autophagy termed mitophagy. PINK1 accumulates on the surface of dysfunctional mitochondria where it simultaneously recruits and activates Parkin's E3 ubiquitin ligase activity. This forms the basis of multiple signaling events that culminate in engulfment of damaged mitochondria within autophagosomes and degradation by lysosomes. This review discusses the molecular signals of PINK1/Parkin mitophagy and the ubiquitin code that drives not only Parkin recruitment and activation by PINK1 but also the downstream signaling events of mitophagy.
Purpose
Circulating microRNAs (miRNAs) are potential diagnostic biomarkers for breast cancer (BC). The application of miRNA panels could improve the performance of screening tests. Here, we ...integrated bioinformatic tools and meta-analyses to select circulating miRNAs with high diagnostic accuracy and combined these markers to develop diagnostic panels for BC.
Methods
Analyses across databases were performed to identify potential BC-related circulating miRNAs. Next, a comprehensive meta-analysis was conducted for each miRNA following the PRISMA guidelines. An electronic and manual search for relevant literature was carried out by two reviewers through PubMed, ScienceDirect, Biomed Central, and Google Scholar. The quality of the included studies was assessed using the QUADAS-2, and the statistical analyses were performed using R software 4.1.1. Finally, the accurate biomarkers confirmed through meta-analyses were combined into diagnostic models for BC.
Results
Twenty-seven circulating miRNAs were identified as BC-related by bioinformatic tools. After screening, only 10 miRNAs presented in 45 studies were eligible for meta-analyses. By assessing pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, 8 miRNAs (miR-21, miR-30b, miR-125b, miR-145, miR221 miR-222, and miR-335) were revealed as promising BC diagnostic biomarkers. Two panels constructed from these miRNAs showed excellent diagnostic accuracy for BC, with areas under the SROC curve of 0.917 and 0.944.
Conclusion
We identified 8 potential circulating miRNAs and 2 diagnostic models that are useful for diagnosing BC. However, the established miRNA panels have not been tested in any experimental studies and thus should be validated in large case–control studies for clinical use.
An extended isogeometric element formulation (XIGA) for analysis of through-the-thickness cracks in thin shell structures is developed. The discretization is based on Non-Uniform Rational B-Splines ...(NURBS). The proposed XIGA formulation can reproduce the singular field near the crack tip and the discontinuities across the crack. It is based on the Kirchhoff–Love theory where C1-continuity of the displacement field is required. This condition is satisfied by the NURBS basis functions. Hence, the formulation eliminates the need of rotational degrees of freedom or the discretization of the director field facilitating the enrichment strategy. The performance and validity of the formulation is tested by several benchmark examples.
•An extended isogeometric element formulation (XIGA) for analysis of through-the-thickness cracks in thin shell structures.•XIGA can reproduce the singular field near the crack tip and the discontinuities across the crack.•NURBS basis possesses C1-continuity required by Kirchhoff–Love theory without additional rotational degrees of freedom.
Basilar artery occlusion stroke is known to have poor outcome with a high rate of morbidity and mortality despite best medical therapy. Since the original report of intra-arterial therapy for basilar ...artery occlusion in 1983, two recent randomized trials comparing endovascular therapy versus best medical management were completed on a large scale, BASICS (Basilar Artery International Cooperation Study) and the BEST trial (Basilar Artery Occlusion Endovascular Intervention Versus Standard Medical Treatment), both of which demonstrated equivocal benefit of the two modalities. In this commentary, we comment and highlight important lessons related to basilar occlusion stroke as learned from the BASICS and BEST randomized trials.
We present an isogeometric thin shell formulation for multi-patches based on rational splines over hierarchical T-meshes (RHT-splines). Nitsche’s method is employed to efficiently couple the patches. ...The RHT-splines have the advantages of allowing a computationally feasible local refinement, are free from linear dependence, possess high-order continuity and satisfy the partition of unity and non-negativity. In addition, the C1 continuity of the RHT-splines avoids the rotational degrees of freedom. The good performance of the present method is demonstrated by a number of numerical examples.
•We present a multi-patch isogeometric large deformation thin shell formulation based on RTH splines. It is an extension of our previous work on RHT-spline shells to large deformations and multiple patches. The coupling is based on Nitsche’s method and allows also coupling of a shell to a solid model.•Furthermore, we present a stress recovery technique to drive the adaptive h-refinement procedure in isogeometric thin structures.•The method is validated for several linear and non-linear benchmark problems including the pinched cylinder and hemispherical shell, a wind turbine rotor accounting for large deformations, a hemispherical shell with a stiffener and a pinched cylinder considering large deformations.
In a trial conducted in China, patients with large cerebral infarctions as determined by imaging criteria within 24 hours after onset had better outcomes with endovascular therapy than with medical ...therapy alone.
The hyperdense vessel sign on CT and susceptibility vessel sign (SVS) on MRI have been associated with red blood cell-rich clots and have been reported to be associated with better reperfusion rates ...and better response to stent-retrievers as the first-line modality.3 In the Adaptive Endovascular Strategy to the Clot MRI in Large Intracranial Vessel Occlusion (VECTOR) study, Romain Bourcier and colleagues aimed to compare the safety and efficacy of a stent retriever plus contact aspiration (combined technique) versus contact aspiration alone in patients with SVS-positive occlusions.4 VECTOR was a randomised, open-label study with blinded-endpoint evaluation. 521 patients (≥18 years of age) with SVS-positive occlusion of the internal carotid artery or middle cerebral artery (M1 or proximal M2 segment) on pretreatment MRI and arterial puncture within 24 h of symptom onset were randomly assigned 1:1 to first-line endovascular therapy with either the combined technique (n=263) or contact aspiration alone (n=258), in France. The randomised study design and blinded endpoint evaluation, along with the low crossover rates, ensure rigorous results. TNN has participated in advisory boards for Aruna Bio and Brainomix (one time); is co-Principal Investigator of the SUMMIT MAX and PICASSO trials; has participated in data safety monitoring boards for the CREST2, SELECT2, TESLA, TATUM, WE-TRUST, and HEMERA trials (all unpaid except CREST2; payment from the National Institutes of Health); is a member of the clinical events committee for ENDOLOW (payment from Emory University); is an Associate Editor of Stroke; and is President of the Society of Vascular and Interventional Neurology.
In 1981, the dismal outcomes of patients with basilar artery occlusion (BAO) inspired the first reports of intra-arterial thrombolytic treatment in BAO. These reports were among the first to ...conceptualize that opening an artery could help patients with large vessel occlusion stroke. Whereas multiple anterior circulation LVO trials demonstrated the efficacy of endovascular therapy starting in 2014, proof of benefit for BAO was lacking until 2022. In this commentary, we reflect on how the BASICS (Basilar Artery International Cooperation Study) and BEST (Basilar Artery Occlusion: Endovascular Interventions vs Standard Medical Treatment) trials lay the foundations for clinical trials in BAO, subsequently leading to the positive results of the ATTENTION (Endovascular Treatment for Acute Basilar-Artery Occlusion) and BAOCHE (Basilar Artery Occlusion Chinese Endovascular) trials.
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