Accumbal acetylcholine signals associative salience.

Learning in dynamic environments requires animals to not only associate cues with outcomes but also to determine cue salience, which modulates how quickly related associations are updated. While dopamine (DA) in the nucleus accumbens core (NAcc) has been implicated in learning associations, the mechanisms of salience are less understood. Here, we tested the hypothesis that acetylcholine (ACh) in the NAcc encodes cue salience.

Spatiotemporal control of translation in live zebrafish embryos via photoprotected mRNAs.

Translation of mRNA into protein is a fundamental process and tightly controlled during development. Several mechanisms acting on the mRNA level regulate when and where an mRNA is expressed. To explore the effects of conditional and transient gene expression in a developing organism, it is vital to experimentally enable abrogation and restoration of translation.

Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE.

Systemic lupus erythematosus (SLE) patients are 90% women and over three times more likely to die of cardiovascular disease than women in the general population. Chest pain with no obstructive cardiac disease is associated with coronary microvascular disease (CMD), where narrowing of the small blood vessels can lead to ischemia, and frequently reported by SLE patients. Using whole blood RNA samples, we asked whether gene signatures discriminate SLE patients with coronary microvascular dysfunction (CMD) on cardiac MRI (n = 4) from those without (n = 7) and whether any signaling pathway is linked to the underlying pathobiology of SLE CMD.

Enhancing hepatocellular carcinoma therapy with DOX-loaded SiO nanoparticles via mTOR-TFEB pathway autophagic flux inhibition.

Chemotherapeutic drugs often fail to provide long-term efficacy due to their lack of specificity and high toxicity. To enhance the biosafety and reduce the side effects of these drugs, various nanocarrier delivery systems have been developed. In this study, we loaded the anticancer drug doxorubicin (DOX) and an MRI contrast agent into silica nanoparticles, coating them with pH-responsive and tumor cell-targeting polymers.

IgA class switching enhances neutralizing potency against SARS-CoV-2 by increased antibody hinge flexibility.

IgA antibodies are critical components of the mucosal immune barrier, providing essential first-line defense against viral infections. In this study, we investigated the impact of antibody class switching on neutralization efficacy by engineering recombinant antibodies of different isotypes (IgA1, IgG1) with identical variable regions from SARS-CoV-2 convalescent patients. A potent, broad-spectrum neutralizing monoclonal antibody CAV-C65 exhibited a ten-fold increase in neutralization potency upon switching from IgG1 to IgA1 monomer.

How spinal GABAergic circuits modulate cerebral processing of postsurgical pain.

Post-surgical pain affects millions each year, hindering recovery and quality of life. Surgical procedures cause tissue damage and inflammation, leading to peripheral and central sensitization, resulting in pain at rest or hyperalgesia to mechanical stimuli, among others. In a rat model for post-surgical pain, spinal GABAergic transmission via GABA receptors reduces mechanical hypersensitivity but has no effect on pain at rest.

Immunosuppressive therapy to treat newly diagnosed primary heart involvement in patients with systemic sclerosis: An Italian cardiac magnetic resonance based study.

Background: Primary heart involvement (pHI) is frequent in systemic sclerosis (SSc), and is associated with a poor prognosis. Therapeutic strategies to treat SSc-pHI are not yet defined.

Objectives: To evaluate the efficacy of immunosuppressive therapy on cardiac magnetic resonance (CMR) features in patients with CMR-proven SSc-pHI.

Abnormal sensory processing cortex in insomnia disorder: a degree centrality study.

Insomnia disorder is a significant global health concern. This research aimed to explore the pathogenesis of insomnia disorder using static and dynamic degree centrality methods at the voxel level. A total of 29 patients diagnosed with insomnia disorder and 28 healthy controls were ultimately included to examine differences in degree centrality between the two groups.

Quantitative pre-clinical imaging of hypoxia and vascularity using MRI and PET.

During hypoxia, tissues are subjected to an inadequate oxygen supply, disrupting the balance needed to maintain normal function. This deficiency can occur due to reduced oxygen delivery caused by impaired blood flow or a decline in the blood's ability to carry oxygen. In tumors, hypoxia and vascularization play crucial roles, shaping their microenvironments and influencing cancer progression, response to treatment and metastatic potential.

Non-alcoholic fatty liver disease is associated with structural covariance network reconfiguration in cognitively unimpaired adults with type 2 diabetes.

Type 2 diabetes (T2D) is often accompanied by non-alcoholic fatty liver disease (NAFLD), both of which are related to brain damage and cognitive impairment. However, cortical structural alteration and its relationship with metabolism and cognition in T2D with NAFLD (T2NAFLD) and without NAFLD (T2noNAFLD) remain unclear. The brain MRI scans, clinical measures and neuropsychological test were evaluated in 50 normal controls (NC), 73 T2noNAFLD, and 58 T2NAFLD.

Hemodynamic Relevance Evaluation of Coronary Artery Anomaly During Stress Using FFR/IVUS in an Artificial Twin.

Anomalous aortic origin of coronary artery can lead to ischemia. Due to the limitations of invasive catheterization dobutamine stress testing, an alternative noninvasive approach is desired. A 65-year-old woman with atypical chest pain was referred for coronary computed tomography angiography.

The Effect of Sensory Reweighting on Postural Control and Cortical Activity in Parkinson's Disease: A Pilot Study.

Objective: To investigate the effects of sensory reweighting on postural control and cortical activity in individuals with Parkinson's disease (PD) compared to age-matched controls using a virtual reality sensory organization test (VR-SOT).

Design: Cross-sectional pilot study.

Setting: University research laboratory.

Improving timing resolution of BGO for TOF-PET: a comparative analysis with and without deep learning.

Background: The renewed interest in BGO scintillators for TOF-PET is driven by the improved Cherenkov photon detection with new blue-sensitive SiPMs. However, the slower scintillation light from BGO causes significant time walk with leading edge discrimination (LED), which degrades the coincidence time resolution (CTR). To address this, a time walk correction (TWC) can be done by using the rise time measured with a second threshold.

Evaluation of Intensive Statins and Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Intracranial Artery Plaque Stability: A Prospective Single-Arm Study.

Background: Intracranial atherosclerotic stenosis is a leading cause of ischemic stroke and recurrent events due to plaque instability. High-resolution magnetic resonance imaging identifies plaque enhancement as a key marker of instability. This study evaluated the efficacy of combined high-intensity statins and proprotein convertase subtilisin/kexin type 9 inhibitors in plaque stabilization.

The human patellar tendon is mechanically homogenous at its mid-substance.

The human patellar tendon contains distinct fascicle bundles across its mediolateral and anteroposterior regions. Studies have suggested region-specific behaviour during in vivo actions, but it is unclear whether such regional differences result from localized variation in composition and mechanical properties within the tendon itself. Furthermore, the viscoelastic properties of any region of the human patellar tendon have not been well described previously.

Super-photostable organic dye for long-term live-cell single-protein imaging.

Organic dyes play a crucial role in live-cell imaging because of their advantageous properties, such as photostability and high brightness. Here we introduce a super-photostable and bright organic dye, Phoenix Fluor 555 (PF555), which exhibits an order-of-magnitude longer photobleaching lifetime than conventional organic dyes without the requirement of any anti-photobleaching additives. PF555 is an asymmetric cyanine structure in which, on one side, the indole in the conventional Cyanine-3 is substituted with 3-oxo-quinoline.

Revealing excitation-inhibition imbalance in Alzheimer's disease using multiscale neural model inversion of resting-state functional MRI.

Background: Alzheimer's disease (AD) is a serious neurodegenerative disorder without a clear understanding of pathophysiology. Recent experimental data have suggested neuronal excitation-inhibition (E-I) imbalance as an essential element of AD pathology, but E-I imbalance has not been systematically mapped out for either local or large-scale neuronal circuits in AD, precluding precise targeting of E-I imbalance in AD treatment.

Method: In this work, we apply a Multiscale Neural Model Inversion (MNMI) framework to the resting-state functional MRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to identify brain regions with disrupted E-I balance in a large network during AD progression.

Safety and Efficacy of Selexipag for Pediatric Pulmonary Arterial Hypertension in Japanese Patients - An Open-Label Phase 2 Study.

Background: Selexipag, an oral prostacyclin (PGI) receptor agonist, is approved for adult patients with pulmonary arterial hypertension (PAH). This study evaluated the efficacy and safety of selexipag for Japanese pediatric patients with PAH.

Methods And Results: The study enrolled 6 patients who received selexipag twice daily at an individualized dose based on body weight; maintenance doses were determined for each patient by 12 weeks after starting administration.

Systematic evaluation of adhesives for implant fixation in multimodal functional brain MRI.

Objective: Invasive multimodal fMRI in rodents is often compromised by susceptibility artifacts from adhesives used to secure cranial implants. We hypothesized that adhesive type, shape, and field strength significantly affect susceptibility artifacts, and systematically evaluated various adhesives.

Materials And Methods: Thirty-one adhesives were applied in constrained/unconstrained geometries and imaged with T2*-weighted EPI at 7.

Hemodynamic response of the aortic valve during dobutamine onset then progressive aortic banding.

An increasing number of procedures over the past two decades for aortic stenosis (AS) reflects the combination of an aging population and less invasive transcatheter options. As a result, the hemodynamics of the aortic valve (AV) have gained renewed interest to understand its behavior and to optimize patient selection. We studied the hemodynamic relationship between pressure loss (ΔP) and transvalvular flow (Q) of the normal AV as well as the impact of a variable supravalvular stenosis.

Patch-Wise Deep Learning Method for Intracranial Stenosis and Aneurysm Detection-the Tromsø Study.

Intracranial atherosclerotic stenosis (ICAS) and intracranial aneurysms are prevalent conditions in the cerebrovascular system. ICAS causes a narrowing of the arterial lumen, thereby restricting blood flow, while aneurysms involve the ballooning of blood vessels. Both conditions can lead to severe outcomes, such as stroke or vessel rupture, which can be fatal.

Association between impaired diffusion capacity and small airway dysfunction: a cross-sectional study.

Background: Small airway dysfunction (SAD) and impaired diffusion capacity of the lungs for carbon monoxide ( ) are positively associated with a worse prognosis. Individuals with both dysfunctions have been identified in clinical practice and it is unknown whether they have worse health status or need management. We conducted this study to explore the association between SAD and impaired , and the difference between the groups with two dysfunctions, with either one dysfunction and with no dysfunction.

Comparing heart PET scans: an adjustment of Kolmogorov-Smirnov test under spatial autocorrelation.

The principle of independence is a fundamental yet often disregarded assumption in statistical inference. It is observed that the implications of correlations, if not considered, can lead to a conservative estimation of Type I error in the presence of positive linear correlations when utilizing the Kolmogorov-Smirnov (KS) test. Conversely, negative linear correlations may engender a liberal estimation of Type I error.

imaging of subacute myocardial infarction with ultra-short echo time 3D quantitative T- and T -mapping magnetic resonance imaging in mice.

Aims: The aim of this study was to develop an ultra-short echo time 3D magnetic resonance imaging (MRI) method for imaging subacute myocardial infarction (MI) quantitatively and in an accelerated way. Here, we present novel 3D T- and T -weighted Multi-Band SWeep Imaging with Fourier Transform and Compressed Sensing (MB-SWIFT-CS) imaging of subacute MI in mice hearts .

Methods And Results: Relaxation time-weighted and under-sampled 3D MB-SWIFT-CS MRI were tested with manganese chloride (MnCl) phantom and mice MI model.