Nerve conduction features may serve as a diagnostic clue for neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease is a neurodegenerative disorder with a wide phenotypic spectrum, including peripheral neuropathy. This study aims to characterize the nerve conduction features and proposes an electrophysiological criterion to assist the diagnosis of neuronal intranuclear inclusion disease. In this study, nerve conduction studies were performed in 50 genetically confirmed neuronal intranuclear inclusion disease patients, 200 age- and sex-matched healthy controls and 40 patients with genetically unsolved leukoencephalopathy.

Exploring the optimal lower blood pressure boundary during endovascular thrombectomy in patients with large vessel occlusion.

Background: Current guidelines advocate for maintaining BP level below 180/105 mmHg during EVT, determining the safe lower boundary remains primarily consensus-driven by experts. This study aims to delve into the correlation between various targets of lower boundary for systolic and diastolic BP (SBP and DBP) during EVT and 3-month functional outcomes.

Methods: A cohort study was conducted across two EVT-capable centers, enrolling patients with large artery occlusion undergoing EVT within 8 h of stroke onset.

Activation of STING by the novel liposomal TLC388 enhances the therapeutic response to anti-PD-1 antibodies in combination with radiotherapy.

Current immune checkpoint inhibiters (ICIs) have contrasting clinical results in poorly immunogenic cancers such as microsatellite-stable colorectal cancer (MSS-CRC). Therefore, understanding and developing the combinational therapeutics for ICI-unresponsive cancers is critical. Here, we demonstrated that the novel topoisomerase I inhibitor TLC388 can reshape the tumor immune landscape, corroborating their antitumor effects combined with radiotherapy as well as immunotherapy.

Effect of air-liquid interface on cultured human intestinal epithelial cells.

The intestinal epithelium is a dynamic barrier that allows the selective exchange of ions, hormones, proteins, and nutrients. To accomplish this, the intestinal epithelium adopts a highly columnar morphology which is partially lost in submerged culturing systems. To achieve this, small intestinal tissue samples were utilized to obtain human intestinal crypts to form enteroids.

Comparing Efficacy and Safety Between Patients With Atrial Fibrillation Taking Direct Oral Anticoagulants or Warfarin After Direct Oral Anticoagulant Failure.

Background: An increased risk of recurrent stroke is noted in patients with atrial fibrillation despite direct oral anticoagulant (DOAC) use. We investigated the efficacy and safety of treatment with each of 4 different DOACs or warfarin after DOAC failure.

Methods And Results: We retrospectively analyzed patients with atrial fibrillation with ischemic stroke despite DOAC treatment between January 2002 and December 2016.

A Pilot Study to Explore the Improvements in Pulmonary and Cognitive Functions With a Kazoo Intervention Among Middle-Aged and Older Adults in a Rural Community.

Dementia is a leading cause of disability and dependence in older adults worldwide. The aim of this pilot study was to explore the effect of using a kazoo instrument to improve pulmonary function and cognitive reserve in middle-aged and older adults in rural areas. This quasi-experimental study was conducted at two community care stations selected using cluster sampling from a rural district in southern Taiwan.

Prevention of acute GVHD using an orthogonal IL-2/IL-2Rβ system to selectively expand regulatory T cells in vivo.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for patients with hematological disorders and bone marrow (BM) failure syndromes. Graft-versus-host disease (GVHD) remains a leading cause of morbidity posttransplant. Regulatory T cell (Treg) therapies are efficacious in ameliorating GVHD but limited by variable suppressive capacities and the need for a high therapeutic dose.

Podocalyxin-Like Protein 1 Regulates Pluripotency through the Cholesterol Biosynthesis Pathway.

Deciphering signaling mechanisms critical for the extended pluripotent stem cell (EPSC) state and primed pluripotency is necessary for understanding embryonic development. Here, a membrane protein, podocalyxin-like protein 1 (PODXL) as being essential for extended and primed pluripotency, is identified. Alteration of PODXL expression levels affects self-renewal, protein expression of c-MYC and telomerase, and induced pluripotent stem cell (iPSC) and EPSC colony formation.

An In Vivo Study to Evaluate the Efficacy of Blue Shark () Cartilage Collagen as a Cosmetic.

The "blue shark", (class: Chondrichthyes), is a pelagic shark species commonly found in tropical and temperate oceans. This shark is mainly sold in Asian countries as food and as traditional Chinese medicine. According to the Red List of the International Union for the Conservation of Nature, is classified as low-risk to near endangered.

Butyrate induces development-dependent necrotizing enterocolitis-like intestinal epithelial injury via necroptosis.

Background: The accumulation of short-chain fatty acids (SCFAs) from bacterial fermentation may adversely affect the under-developed gut as observed in premature newborns at risk for necrotizing enterocolitis (NEC). This study explores the mechanism by which specific SCFA fermentation products may injure the premature newborn intestine mucosa leading to NEC-like intestinal cell injury.

Methods: Intraluminal injections of sodium butyrate were administered to 14- and 28-day-old mice, whose small intestine and stool were harvested for analysis.

Investigating KIF1A mutations in a Taiwanese cohort with hereditary spastic paraplegia.

Background: Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited neurodegenerative disorders characterized by slowly progressive lower limbs spasticity and weakness. HSP type 30 (SPG30) is a HSP subtype caused by mutations in the kinesin family member 1A gene (KIF1A) and could be either autosomal dominantly or recessively inherited. The aim of this study was to investigate the clinical and genetic features of KIF1A mutations in a Taiwanese HSP cohort.

Metabolic model of necrotizing enterocolitis in the premature newborn gut resulting from enteric dysbiosis.

Necrotizing enterocolitis (NEC) is a leading cause of premature newborn morbidity and mortality. The clinical features of NEC consistently include prematurity, gut dysbiosis and enteral inflammation, yet the pathogenesis remains obscure. Herein we combine metagenomics and targeted metabolomics, with functional and assessment, to define a novel molecular mechanism of NEC.

IL-2 receptor engineering enhances regulatory T cell function suppressed by calcineurin inhibitor.

Clinical trials utilizing regulatory T cell (Treg) therapy in organ transplantation have shown promising results, however, the choice of a standard immunosuppressive regimen is still controversial. Calcineurin inhibitors (CNIs) are one of the most common immunosuppressants for organ transplantation, although they may negatively affect Tregs by inhibiting IL-2 production by conventional T cells. As a strategy to replace IL-2 signaling selectively in Tregs, we have introduced an engineered orthogonal IL-2 (ortho IL-2) cytokine/cytokine receptor (R) pair that specifically binds with each other but does not bind with their wild-type counterparts.

Application of Deep Reinforcement Learning to NS-SHAFT Game Signal Control.

Reinforcement learning (RL) with both exploration and exploit abilities is applied to games to demonstrate that it can surpass human performance. This paper mainly applies Deep Q-Network (DQN), which combines reinforcement learning and deep learning to the real-time action response of NS-SHAFT game with Cheat Engine as the API of game information autonomously. Based on a personal computer, we build an experimental learning environment that automatically captures the NS-SHAFT's frame, which is provided to DQN to decide the action of moving left, moving right, or stay in same location, survey different parameters: such as the sample frequency, different reward function, and batch size, etc.

Detailed risks and characteristics of postepilepsy stroke in non-traumatic adult-onset epilepsy.

Background: Patients with epilepsy have an increased risk of stroke. However, the detailed risk and characteristics of postepilepsy stroke have not been investigated.

Methods: This study utilized the National Health Insurance Research Database in Taiwan.

Muscle Biopsy: A Requirement for Precision Medicine in Adult-Onset Myopathy.

Muscle biopsy is a fundamental procedure to assist the final diagnosis of myopathy. With the recent advances in molecular diagnosis, serology tests, and mechanism-based classification in myopathy, the précised diagnosis for myopathy required the applications of multiple tools. This study intends to reappraise the benefit of muscle biopsy in adult-onset myopathy under the setting of an optimized muscle biopsy protocol and comprehensive serology tests.

Cerebral Venous Thrombosis Mimicking Acute Ischemic Stroke in the Emergency Assessment of Thrombolysis Eligibility: Learning from a Misdiagnosed Case.

Purpose: Cerebral venous thrombosis (CVT) occasionally presents with acute focal neurologic signs, mimicking arterial stroke syndrome. Diagnosing CVT in the setting of thrombolysis eligibility evaluation is challenging. We reported this case to discuss the promptly recognizing CVT in the setting of thrombolysis eligibility evaluation, and review the literature of thrombolytic therapy in CVT patients.

Comparative Analyses of Single-Cell Transcriptomic Profiles between In Vitro Totipotent Blastomere-like Cells and In Vivo Early Mouse Embryonic Cells.

The developmental potential within pluripotent cells in the canonical model is restricted to embryonic tissues, whereas totipotent cells can differentiate into both embryonic and extraembryonic tissues. Currently, the ability to culture in vitro totipotent cells possessing molecular and functional features like those of an early embryo in vivo has been a challenge. Recently, it was reported that treatment with a single spliceosome inhibitor, pladienolide B (plaB), can successfully reprogram mouse pluripotent stem cells into totipotent blastomere-like cells (TBLCs) in vitro.

Invasive Pathobionts Contribute to Colon Cancer Initiation by Counterbalancing Epithelial Antimicrobial Responses.

Background & Aims: Microbiota dysbiosis and mucosa-associated bacteria are involved in colorectal cancer progression. We hypothesize that an interaction between virulent pathobionts and epithelial defense promotes tumorigenesis.

Methods: Chemical-induced CRC mouse model was treated with antibiotics at various phases.

Factors Associated with Cognitive Outcomes After First-Ever Ischemic Stroke: The Impact of Small Vessel Disease Burden and Neurodegeneration.

Background: Differences exist regarding post-stroke cognitive outcomes.

Objective: The aim of this study investigates the potential factors associated with post-stroke cognitive performance and trajectories.

Methods: We performed a prospective cohort study using serial monitoring of cognitive function over a 1-year period after a first-ever ischemic stroke.

Imaging alloreactive T cells provides early warning of organ transplant rejection.

Diagnosis of organ transplant rejection relies upon biopsy approaches to confirm alloreactive T cell infiltration in the graft. Immune molecular monitoring is under investigation to screen for rejection, though these techniques have suffered from low specificity and lack of spatial information. ImmunoPET utilizing antibodies conjugated to radioisotopes has the potential to improve early and accurate detection of graft rejection.

Activation of natural killer T cells enhances the function of regulatory T-cell therapy in suppressing murine GVHD.

Cellular therapy with regulatory T cells (Tregs) has shown promising results for suppressing graft-versus-host disease (GVHD) while preserving graft vs tumor effects in animal models and phase 1/2 clinical trials. However, a paucity of Tregs in the peripheral blood makes it difficult to acquire sufficient numbers of cells and hampers further clinical application. Invariant natural killer T (iNKT) cells constitute another compartment of regulatory cells that ameliorate GVHD through activation of Tregs after their own activation with α-galactosylceramide (α-GalCer) or adoptive transfer.