Phase II Trial of Neoadjuvant Docetaxel/Cisplatin/5-Fluorouracil Combined with Pegteograstim for Unresectable, Locally Advanced Sinonasal Squamous Cell Carcinoma: KCSG HN18-07.

Purpose: The role of neoadjuvant chemotherapy in locally advanced sinonasal squamous cell carcinoma (SNSCC) has not been established prospectively. We conducted a phase II trial of neoadjuvant chemotherapy (NAC) with docetaxel/cisplatin/5-fluorouracil (TPF) in this population.

Materials And Methods: Eligible patients had unresectable, locally advanced SNSCC, defined as T3/4 stage or potential compromise of critical organ function on surgery.

Expansion microscopy of axonemal dyneins in islet primary cilia.

Primary cilia are sensory organelles that mediate critical cellular functions yet are difficult to visualize because of their small size and low abundance. Expansion microscopy (ExM) is an imaging method that physically expands biological specimens using a swellable hydrogel, facilitating downstream imaging of small cellular structures. In this study, we apply ExM with confocal imaging to probe axonemal dynein expression in murine and human pancreatic islets.

Assessing the Impact of Defacing Algorithms on Brain Volumetry Accuracy in MRI Analyses.

Background And Purpose: To ensure data privacy, the development of defacing processes, which anonymize brain images by obscuring facial features, is crucial. However, the impact of these defacing methods on brain imaging analysis poses significant concern. This study aimed to evaluate the reliability of three different defacing methods in automated brain volumetry.

Greater Severity of Steatosis Is Associated with a Higher Risk of Incident Diabetes: A Retrospective Longitudinal Study.

Backgruound: Fatty liver is associated with increased risk of developing type 2 diabetes. We aimed to evaluate whether the severity of hepatic steatosis is associated with incident diabetes.

Methods: We conducted a longitudinal analysis using data from 1,798 participants who underwent a comprehensive health checkup and abdominal computed tomography (CT).

Ferritin Nanoshuttle for Long-Lasting Self-Healing of Phenolic Hydrogels.

Herein, we highlight a novel finding that ferritin can play a crucial role in the "self-healing lifetime" of soft phenolic materials. Ferritin interacts with a catechol-functionalized polymer to form a self-healable and adhesive hydrogel bidirectionally by providing and retrieving Fe. As a result of its unique role as a nanoshuttle to store and release iron, ferritin significantly increases the self-healing lifetime of the hydrogel compared with that afforded by catechol-Fe coordination through direct Fe addition without ferritin.

Alternative Methotrexate Oral Formulation: Enhanced Aqueous Solubility, Bioavailability, Photostability, and Permeability.

The poor aqueous solubility and/or permeability and thereby limited bioavailability largely restricts the pharmaco-therapeutic implications of potent anticancer drugs such as methotrexate (MTX). Furthermore, MTX's inherently unstable nature makes it difficult to develop a viable oral formulation. In this study we developed the spray-dried amorphous inclusion complexes of MTX with native β-cyclodextrin (β-CD) and its derivatives, namely HP-β-CD, M-β-CD, and DM-β-CD to enhance the aqueous solubility, photostability, permeability, and oral bioavailability of MTX in rats.

Fluorescence imaging of beta cell primary cilia.

Primary cilia are slender cell-surface organelles that project into the intercellular space. In pancreatic beta cells, primary cilia coordinate a variety of cell responses including GPCR signaling, calcium influx, and insulin secretion, along with likely many underappreciated roles in islet development and differentiation. To study cilia function in islet biology, direct visualization of primary cilia by microscopic methods is often a necessary first step.

Islet primary cilia motility controls insulin secretion.

Primary cilia are specialized cell-surface organelles that mediate sensory perception and, in contrast to motile cilia and flagella, are thought to lack motility function. Here, we show that primary cilia in human and mouse pancreatic islets exhibit movement that is required for glucose-dependent insulin secretion. Islet primary cilia contain motor proteins conserved from those found in classic motile cilia, and their three-dimensional motion is dynein-driven and dependent on adenosine 5'-triphosphate and glucose metabolism.

Cilia Action in Islets: Lessons From Mouse Models.

Primary cilia as a signaling organelle have garnered recent attention as a regulator of pancreatic islet function. These rod-like sensors exist on all major islet endocrine cell types and transduce a variety of external cues, while dysregulation of cilia function contributes to the development of diabetes. The complex role of islet primary cilia has been examined using genetic deletion targeting various components of cilia.

Automated brain volumetric program measuring regional brain atrophy in diagnosis of mild cognitive impairment and Alzheimer's disease dementia.

A quantitative analysis of brain volume can assist in the diagnosis of Alzheimer's disease (AD) which is ususally accompanied by brain atrophy. With an automated analysis program Quick Brain Volumetry (QBraVo) developed for volumetric measurements, we measured regional volumes and ratios to evaluate their performance in discriminating AD dementia (ADD) and mild cognitive impairment (MCI) patients from normal controls (NC). Validation of QBraVo was based on intra-rater and inter-rater reliability with a manual measurement.

LPIN1 Induces Gefitinib Resistance in EGFR Inhibitor-Resistant Non-Small Cell Lung Cancer Cells.

Drug resistance limits the efficacy of targeted therapies, including tyrosine kinase inhibitors (TKIs); however, a substantial portion of the drug resistance mechanisms remains unexplained. In this study, we identified LPIN1 as a key factor that regulates gefitinib resistance in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) cells. Unlike TKI-sensitive HCC827 cells, gefitinib treatment induced LPIN1 expression and increased diacylglycerol concentration in TKI-resistant H1650 cells, followed by the activation of protein kinase C delta and nuclear factor kappa B (NF-κB) in an LPIN1-dependent manner, resulting in cancer cell survival.

Evolution of magnetic resonance imaging features in cerebral parenchyma from prolonged focal status epilepticus: a case study.

It has rarely been documented that permanent alteration of cerebral structures occurs by focal status epilepticus (FSE). We report the case of a 16-year-old boy with FSE in whom serial T1-weighted magnetic resonance volumetry and conventional magnetic resonance imaging were useful for investigating an evolving pattern of morphological changes during and after the FSE, including cortical laminar necrosis (CLN), increased T2 signal intensities, and marked regional atrophy on the corresponding areas. Despite cessation of FSE after adequate medication (combination therapy including clobazam of 1 mg/kg/day), further significant cerebral atrophy was detected at the limited regions where discrete CLN had occurred during the FSE.

Novel dapagliflozin di-L-proline cocrystal-loaded tablet: preparation, physicochemical characterization, and pharmacokinetics in beagle dogs and mini-pigs.

Dapagliflozin base and a commercial dapagliflozin propanediol hydrate cocrystal (DPF-PDHC) were highly hygroscopic and thermally unstable. In this study, to address this limitation, we prepared a novel dapagliflozin di-L-proline cocrystal (DPF-LPC) and evaluated its physicochemical characterization compared with DPF-PDHC. After the preparation of the DPF-LPC-loaded tablet, its dissolution, stability and bioequivalence in beagle dogs and mini-pigs were assessed.

PKM2 Regulates HSP90-Mediated Stability of the IGF-1R Precursor Protein and Promotes Cancer Cell Survival during Hypoxia.

Insulin-like growth factor-1 receptor (IGF-1R), an important factor in promoting cancer cell growth and survival, is commonly upregulated in cancer cells. However, amplification of the gene is extremely rare in tumors. Here, we have provided insights into the mechanisms underlying the regulation of IGF-1R protein expression.

Moxibustion for treating cancer-related fatigue: A multicenter, assessor-blinded, randomized controlled clinical trial.

Cancer-related fatigue (CRF) is one of the most common chronic symptoms experienced by cancer patients. As moxibustion is a popular traditional therapy for managing fatigue, it can be an alternative strategy to treat CRF as well. Therefore, we rigorously designed a full-scale, multicenter, assessor-blinded, randomized controlled trial to evaluate the efficacy and safety of moxibustion treatment for CRF.

Skin protein-derived peptide-conjugated vesicular nanocargos for selected skin cell targeting and consequent activation.

Several studies have reported that a drug nanocarrier conjugated with ligands having cell binding ability improves drug delivery performance, but multiple cell-targeting and the resultant activation in designated cells has not been investigated yet. This study reports a skin cell multi-targeting vesicular nanocargo system. We selectively conjugated several skin protein-derived cell-targeting peptides (CTPs), including KTTKS, NAP-amide, and Lam332, to amphiphilic polymer-reinforced lipid nanovesicles (PLNVs) to specifically target fibroblasts, melanocytes, and keratinocytes, respectively, through effective association with the corresponding cell membrane receptors.

Development of rebamipide-loaded spray-dried microsphere using distilled water and meglumine: physicochemical characterization and pharmacokinetics in rats.

In this study, a novel rebamipide-loaded spray-dried microsphere (RSM) with enhanced drug solubility and oral bioavailability has been developed utilizing meglumine, an alkalizing agent. The influence of carriers on the drug solubility alone, and the solubility and dissolution of the drug in the RSM was investigated. Among the alkalizing agents and hydrophilic polymers tested, meglumine and polyvinyl alcohol (PVA) showed the highest drug solubility and dissolution rate, respectively.

Tissue-Adhesive Chondroitin Sulfate Hydrogel for Cartilage Reconstruction.

Chondroitin sulfate (CS), the main component of cartilage extracellular matrix, has attracted attention as a biomaterial for cartilage tissue engineering. However, current CS hydrogel systems still have limitations for application in successful cartilage tissue engineering owing to their unsuitable degradation kinetics, insufficient mechanical similarity, and lack of integration with the native cartilage tissue. In this study, using mussel adhesive-inspired catechol chemistry, we developed a functional CS hydrogel that exhibits tunable physical and mechanical properties as well as excellent tissue adhesion for efficient integration with native tissues.

Regeneration of irradiation-damaged esophagus by local delivery of mesenchymal stem-cell spheroids encapsulated in a hyaluronic-acid-based hydrogel.

Radiation therapy (RT) is a typical treatment for head and neck cancers. Generally, prolonged irradiation of the esophagus causes esophageal fibrosis due to increased reactive oxygen species and proinflammatory cytokines. This study was designed to determine whether catechol-functionalized hyaluronic acid (HA-CA) hydrogel-encapsulated human mesenchymal stem-cell spheroids (MSC-SPs) could ameliorate damage to the esophagus in a mouse model of radiation-induced esophageal fibrosis.

CD9 induces cellular senescence and aggravates atherosclerotic plaque formation.

CD9, a 24 kDa tetraspanin membrane protein, is known to regulate cell adhesion and migration, cancer progression and metastasis, immune and allergic responses, and viral infection. CD9 is upregulated in senescent endothelial cells, neointima hyperplasia, and atherosclerotic plaques. However, its role in cellular senescence and atherosclerosis remains undefined.

Decreased Vagal Activity and Deviation in Sympathetic Activity Precedes Development of Diabetes.

Objective: The objective of this study was to examine whether altered heart rate variability (HRV) could predict the risk of diabetes in Asians.

Research Design And Methods: A cohort study was conducted in 54,075 adults without diabetes who underwent 3-min HRV measurement during health checkups between 2011 and 2014 at Kangbuk Samsung Hospital. We analyzed the time domain (SD of the normal-to-normal interval [SDNN] and root mean square differences of successive normal-to-normal intervals [RMSSD]) and the frequency domain (total power, normalized low-frequency power [LF], and normalized high-frequency power [HF] and LF/HF ratio).

Primary cilia control glucose homeostasis via islet paracrine interactions.

Pancreatic islets regulate glucose homeostasis through coordinated actions of hormone-secreting cells. What underlies the function of the islet as a unit is the close approximation and communication among heterogeneous cell populations, but the structural mediators of islet cellular cross talk remain incompletely characterized. We generated mice specifically lacking β-cell primary cilia, a cellular organelle that has been implicated in regulating insulin secretion, and found that the β-cell cilia are required for glucose sensing, calcium influx, insulin secretion, and cross regulation of α- and δ-cells.