Prolonged Venous Transit on Perfusion Imaging is Associated with Longer Lengths of Stay in Acute Large Vessel Occlusions.

Background And Purpose: Prolonged venous transit (PVT+) is a marker of venous outflow; it is defined as the presence or absence of time-to-maximum ≥10 seconds timing in either the superior sagittal sinus or torcula. This novel perfusion imaging-based metric has been associated with higher odds of mortality and lower odds of functional recovery. This study aims to assess the relationship between PVT on admission perfusion imaging and length of hospital stay in large vessel occlusion strokes successfully reperfused with mechanical thrombectomy.

Cephalopod-inspired jetting devices for gastrointestinal drug delivery.

Needle-based injections currently enable the administration of a wide range of biomacromolecule therapies across the body, including the gastrointestinal tract, through recent developments in ingestible robotic devices. However, needles generally require training, sharps management and disposal, and pose challenges for autonomous ingestible systems. Here, inspired by the jetting systems of cephalopods, we have developed and evaluated microjet delivery systems that can deliver jets in axial and radial directions into tissue, making them suitable for tubular and globular segments of the gastrointestinal tract.

Interspecies-chimera machine vision with polarimetry for real-time navigation and anti-glare pattern recognition.

Cutting-edge humanoid machine vision merely mimics human systems and lacks polarimetric functionalities that convey the information of navigation and authentic images. Interspecies-chimera vision reserving multiple hosts' capacities will lead to advanced machine vision. However, implementing the visual functions of multiple species (human and non-human) in one optoelectronic device is still elusive.

Integrated global assessment of the natural forest carbon potential.

Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system. Remote-sensing estimates to quantify carbon losses from global forests are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced and satellite-derived approaches to evaluate the scale of the global forest carbon potential outside agricultural and urban lands.

The global biogeography of tree leaf form and habit.

Understanding what controls global leaf type variation in trees is crucial for comprehending their role in terrestrial ecosystems, including carbon, water and nutrient dynamics. Yet our understanding of the factors influencing forest leaf types remains incomplete, leaving us uncertain about the global proportions of needle-leaved, broadleaved, evergreen and deciduous trees. To address these gaps, we conducted a global, ground-sourced assessment of forest leaf-type variation by integrating forest inventory data with comprehensive leaf form (broadleaf vs needle-leaf) and habit (evergreen vs deciduous) records.

Native diversity buffers against severity of non-native tree invasions.

Determining the drivers of non-native plant invasions is critical for managing native ecosystems and limiting the spread of invasive species. Tree invasions in particular have been relatively overlooked, even though they have the potential to transform ecosystems and economies. Here, leveraging global tree databases, we explore how the phylogenetic and functional diversity of native tree communities, human pressure and the environment influence the establishment of non-native tree species and the subsequent invasion severity.

CCND2 Modified mRNA Activates Cell Cycle of Cardiomyocytes in Hearts With Myocardial Infarction in Mice and Pigs.

Background: Experiments in mammalian models of cardiac injury suggest that the cardiomyocyte-specific overexpression of CCND2 (cyclin D2, in humans) improves recovery from myocardial infarction (MI). The primary objective of this investigation was to demonstrate that our specific modified mRNA translation system (SMRTs) can induce CCND2 expression in cardiomyocytes and replicate the benefits observed in other studies of cardiomyocyte-specific CCND2 overexpression for myocardial repair.

Methods: The CCND2-cardiomyocyte-specific modified mRNA translation system (cardiomyocyte SMRTs) consists of 2 modRNA constructs: one codes for CCND2 and contains a binding site for L7Ae, and the other codes for L7Ae and contains recognition elements for the cardiomyocyte-specific microRNAs miR-1 and miR-208.

High-Throughput Screening Assay for Detecting Drug-Induced Changes in Synchronized Neuronal Oscillations and Potential Seizure Risk Based on Ca Fluorescence Measurements in Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neuronal 2D and 3D Cultures.

Drug-induced seizure liability is a significant safety issue and the basis for attrition in drug development. Occurrence in late development results in increased costs, human risk, and delayed market availability of novel therapeutics. Therefore, there is an urgent need for biologically relevant, in vitro high-throughput screening assays (HTS) to predict potential risks for drug-induced seizure early in drug discovery.

Inhibition of fibroblast activation protein ameliorates cartilage matrix degradation and osteoarthritis progression.

Fibroblast activation protein (Fap) is a serine protease that degrades denatured type I collagen, α2-antiplasmin and FGF21. Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin (Oln). Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis (RA).

MRI assessment of cerebral oxygen extraction fraction in the medial temporal lobe.

The medial temporal lobe (MTL) is a key area implicated in many brain diseases, such as Alzheimer's disease. As a functional biomarker, the oxygen extraction fraction (OEF) of MTL may be more sensitive than structural atrophy of MTL, especially at the early stages of diseases. However, there is a lack of non-invasive techniques to measure MTL-OEF in humans.

Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2.

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants.

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study.

Background: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort.

Methods: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020.

Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative.

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group.

Decision Making of Artificial Nutrition and Hydration for Cancer Patients at Terminal Stage-A Systematic Review of the Views From Patients, Families, and Healthcare Professionals.

Background: Decision making on nutrition and hydration for cancer patients during terminal stage cause critical impacts toward patient's comfort and living quality. The management of nutrition is the main dilemma that arises in these final situations and has been the subject of intense debate over the last few decades.

Aim: To find the views of patients, families, and healthcare professionals related to how decisions are made when cancer patients are at terminal stage.

Monosomy X in Female Mice Influences the Regional Formation and Augments the Severity of Angiotensin II-Induced Aortopathies.

Objective: Turner syndrome women (monosomy X) have high risk of aortopathies consistent with a role for sex chromosomes in disease development. We demonstrated that sex chromosomes influence regional development of Ang II (angiotensin II)-induced aortopathies in mice. In this study, we determined if the number of X chromosomes regulates regional development of Ang II-induced aortopathies.

A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent β-Thalassemia.

Background: Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients.

Methods: In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.

Gene Therapy for Catecholaminergic Polymorphic Ventricular Tachycardia by Inhibition of Ca/Calmodulin-Dependent Kinase II.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited cardiac arrhythmia characterized by adrenergically triggered arrhythmias, is inadequately treated by current standard of care. Ca/calmodulin-dependent protein kinase II (CaMKII), an adrenergically activated kinase that contributes to arrhythmogenesis in heart disease models, is a candidate therapeutic target in CPVT. However, translation of CaMKII inhibition has been limited by the need for selective CaMKII inhibition in cardiomyocytes.

Broadband achromatic dielectric metalenses.

Metasurfaces offer a unique platform to precisely control optical wavefronts and enable the realization of flat lenses, or metalenses, which have the potential to substantially reduce the size and complexity of imaging systems and to realize new imaging modalities. However, it is a major challenge to create achromatic metalenses that produce a single focal length over a broad wavelength range because of the difficulty in simultaneously engineering phase profiles at distinct wavelengths on a single metasurface. For practical applications, there is a further challenge to create broadband achromatic metalenses that work in the transmission mode for incident light waves with any arbitrary polarization state.

Drug Screening of Human GBM Spheroids in Brain Cancer Chip.

Glioblastoma multiforme (GBM), an extremely invasive and high-grade (grade IV) glioma, is the most common and aggressive form of brain cancer. It has a poor prognosis, with a median overall survival of only 11 months in the general GBM population and 14.6 to 21 months in clinical trial participants with standard GBM therapies, including maximum safe craniotomy, adjuvant radiation, and chemotherapies.

Histological Changes in the Rat Femoral Artery Following the Use of the Empty-and-Refill Test.

Background:  This study examines the effects of the empty-and-refill patency test on rat femoral arteries in the longer postoperative time period.

Methods:  A simple arterial anastomosis was performed bilaterally on 20 rats. The empty-and-refill test was performed unilaterally in all rats, leaving the contralateral artery as an internal control.

Altenusin, a Nonsteroidal Microbial Metabolite, Attenuates Nonalcoholic Fatty Liver Disease by Activating the Farnesoid X Receptor.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease. The incidence of NAFLD has increased steadily due to its close association with the global epidemic of obesity and type 2 diabetes. However, there is no effective pharmacological therapy approved for NAFLD.