High-density mapping in catheter ablation for atrial fibrillation in Asia Pacific region: An observational study.

Background: Few clinical studies of atrial fibrillation (AF) have focused on Asian patients; data are lacking on current mapping and ablation strategies in the Asia Pacific region (APAC).

Objective: The HD Mapping Observational Study (NCT04022954) was designed to characterize electroanatomic mapping (EAM) with market-released high-density mapping (HDM) catheters in subjects with AF in APAC.

Methods: Subjects undergoing HDM and indicated for radiofrequency ablation (RFA) to treat AF were prospectively enrolled in APAC.

Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear.

Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning.

Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental and deep learning pipeline to comprehensively quantify the targeting of nanocarriers throughout the whole mouse body at single-cell resolution. SCP-Nano reveals the tissue distribution patterns of lipid nanoparticles (LNPs) after different injection routes at doses as low as 0.

A first-in-human phase 1/2 dose-escalation study of MAK683 (EED inhibitor) in patients with advanced malignancies.

Purpose: MAK683, a first-in-class and highly selective allosteric inhibitor of the embryonic ectoderm development subunit of polycomb repressive complex 2, has shown sustained antitumor activity in tumor xenograft models. This first-in-human phase 1/2 study evaluated the safety, pharmacokinetics (PK), and clinical activity of single-agent MAK683 in advanced malignancies.

Methods: MAK683 was administered fasted once daily or twice daily continuously in 28-day treatment cycles.

Genetically engineered biomimetic ATP-responsive nanozyme for the treatment of cardiac fibrosis.

Background: Cardiac fibrosis plays a critical role in the progression of various forms of heart disease, significantly increasing the risk of sudden cardiac death. However, currently, there are no therapeutic strategies available to prevent the onset of cardiac fibrosis.

Methods And Results: Here, biomimetic ATP-responsive nanozymes based on genetically engineered cell membranes are adapted to specifically recognize activated cardiac fibroblasts (CFs) for the treatment of cardiac fibrosis.

Correlation Analysis Between Cortical Structural Features and Acoustic Features in Patients With Parkinson's Disease.

Purpose: Parkinson disease (PD) is a progressive neurodegenerative disease. The aim of this study is to investigate the association between acoustic and cortical brain features in Parkinson's disease patients.

Methods: We recruited 19 (eight females, 11 males) Parkinson's disease patients and 19 (eight females, 11 males) healthy subjects to participate in the experiment.

Roseburia intestinalis-derived butyrate alleviates neuropathic pain.

Approximately 20% of patients with shingles develop postherpetic neuralgia (PHN). We investigated the role of gut microbiota in shingle- and PHN-related pain. Patients with shingles or PHN exhibited significant alterations in their gut microbiota with microbial markers predicting PHN development among patients with shingles.

DNMT3a Downregulation Ttriggered Upregulation of GABA Receptor in the mPFC Promotes Paclitaxel-Induced Pain and Anxiety in Male Mice.

Chemotherapeutic agents, such as paclitaxel (PTX), induce neuroplastic changes and alter gene expression in the prefrontal cortex (PFC), which may be associated with chemotherapy-induced pain and negative emotions. Notably, DNA methylation undergoes adaptive changes in neurological disorders, emerging as a promising target for neuromodulation. In this study, systemic administration of PTX leads to a decrease in the expression of the DNA methyltransferase DNMT3a, while concurrently upregulating the expression of Gabrb1 mRNA and its encoded GABARβ1 protein in the medial PFC (mPFC) of male mice.

A modular platform for bioluminescent RNA tracking.

A complete understanding of RNA biology requires methods for tracking transcripts in vivo. Common strategies rely on fluorogenic probes that are limited in sensitivity, dynamic range, and depth of interrogation, owing to their need for excitation light and tissue autofluorescence. To overcome these challenges, we report a bioluminescent platform for serial imaging of RNAs.

Short-term Effects of Pulsed Electromagnetic Field Therapy for Achilles Tendinopathy: A Randomized Controlled Trial.

Background: Pulsed electromagnetic field (PEMF) therapy is a potential nonoperative treatment for Achilles tendinopathy, but the current published literature on its effects is sparse.

Purpose: To evaluate the therapeutic efficacy of PEMF therapy and eccentric exercise for Achilles tendinopathy.

Study Design: Randomized controlled trial; Level of evidence, 1.

sGC stimulator (BAY 41-8543) combined with PDE9 inhibitor (BAY 73-6691) reduces renal fibrosis in 5/6 nephrectomized rats.

Renal fibrosis is closely related to the prognosis of chronic kidney disease (CKD). The increase in cGMP reduces renal fibrosis. Soluble guanylate cyclase (sGC) and phosphodiesterase (PDE) are key enzymes that maintain cGMP levels.

Arginine vasopressin induces analgesic effects and inhibits pyramidal cells in the anterior cingulate cortex in spared nerve injured mice.

Neuropathic pain (NP) is a severe disease caused by a primary disease or lesion affecting the somatosensory nervous system. It is reported that NP is related to the increased activity of glutamatergic pyramidal cells and changed neural oscillations in the anterior cingulate cortex (ACC). Arginine vasopressin (AVP), a neurohypophyseal hormone, has been shown to cause pain-alleviating effects when applied to the peripheral system.

Shear-Sensing by C-Reactive Protein: Linking Aortic Stenosis and Inflammation.

Background: CRP (C-reactive protein) is a prototypical acute phase reactant. Upon dissociation of the pentameric isoform (pCRP [pentameric CRP]) into its monomeric subunits (mCRP [monomeric CRP]), it exhibits prothrombotic and proinflammatory activity. Pathophysiological shear rates as observed in aortic valve stenosis (AS) can influence protein conformation and function as observed with vWF (von Willebrand factor).

A (CMe)/enolamido lutetium dinitrogen complex promoted by deprotonation on the amidinate ligand.

Selective deprotonation of the amidinate ligand in lutetium dinitrogen complex [{Cp*{MeC(NPr)}Lu}(μ-η:η-N)][K(crypt)] (Cp* = (CMe), crypt = 2,2,2-cryptand) afforded the novel Cp*/enolamido lutetium dinitrogen complex [{Cp*{HCC(NPr)}Lu}(μ-η:η-N)K][K(crypt)]. Due to the skeleton tension, a further rearrangement was confirmed with the formation of [{Cp*K{HCC(NPr)}Cp*Lu}(μ-η:η-N)][K(crypt)].

Electrolyte Design Enables Stable and Energy-Dense Potassium-Ion Batteries.

Free from strategically important elements such as lithium, nickel, cobalt, and copper, potassium-ion batteries (PIBs) are heralded as promising low-cost and sustainable electrochemical energy storage systems that complement the existing lithium-ion batteries (LIBs). However, the reported electrochemical performance of PIBs is still suboptimal, especially under practically relevant battery manufacturing conditions. The primary challenge stems from the lack of electrolytes capable of concurrently supporting both the low-voltage anode and high-voltage cathode with satisfactory Coulombic efficiency (CE) and cycling stability.

Empathic pain: Underlying neural mechanism.

Empathy is usually regarded as the ability to perceive the emotional state of others, which is an altruistic motivation to promote prosocial behavior and thus plays a key role in human life and social development. Empathic pain-the capacity to feel and understand the pain of others-constitutes a significant aspect in the study of empathy behaviors. For an extended duration, investigations into empathic pain have predominantly centered on human neuroimaging studies.

High-frequency terahertz stimulation alleviates neuropathic pain by inhibiting the pyramidal neuron activity in the anterior cingulate cortex of mice.

Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system and is characterized by abnormal hypersensitivity to stimuli and nociceptive responses to non-noxious stimuli, affecting approximately 7-10% of the general population. However, current first-line drugs like non-steroidal anti-inflammatory agents and opioids have limitations, including dose-limiting side effects, dependence, and tolerability issues. Therefore, developing new interventions for the management of NP is urgent.

AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients with MTAP-Deleted Cancers.

One of the most robust synthetic lethal interactions observed in multiple functional genomic screens has been the dependency on protein arginine methyltransferase 5 (PRMT5) in cancer cells with MTAP deletion. We report the discovery of the clinical stage MTA-cooperative PRMT5 inhibitor AMG 193, which preferentially binds PRMT5 in the presence of MTA and has potent biochemical and cellular activity in MTAP-deleted cells across multiple cancer lineages. In vitro, PRMT5 inhibition induces DNA damage, cell cycle arrest, and aberrant alternative mRNA splicing in MTAP-deleted cells.

Datopotamab-deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial.

Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody-drug conjugate, datopotamab-deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer.