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Intestinal epithelial integrity is commonly disrupted in patients with critical disorders, but the exact underlying mechanisms are unclear. Long noncoding RNAs transcribed from ultraconserved regions (T-UCRs) control different cell functions and are involved in pathologies. Here, we investigated the role of T-UCRs in intestinal epithelial homeostasis and identified T-UCR uc.230 as a major regulator of epithelial renewal, apoptosis, and barrier function. Compared with controls, intestinal mucosal tissues from patients with ulcerative colitis and from mice with colitis or fasted for 48 hours had increased levels of uc.230. Silencing uc.230 inhibited the growth of intestinal epithelial cells (IECs) and organoids and caused epithelial barrier dysfunction. Silencing uc.230 also increased IEC vulnerability to apoptosis, whereas increasing uc.230 levels protected IECs against cell death. In mice with colitis, reduced uc.230 levels enhanced mucosal inflammatory injury and delayed recovery. Mechanistic studies revealed that uc.230 increased CUG-binding protein 1 (CUGBP1) by acting as a natural decoy RNA for miR-503, which interacts with Cugbp1 mRNA and represses its translation. These findings indicate that uc.230 sustains intestinal mucosal homeostasis by promoting epithelial renewal and barrier function and that it protects IECs against apoptosis by serving as a natural sponge for miR-503, thereby preserving CUGBP1 expression.

Abstract Background Tumor lysis syndrome (TLS) is a life‐threatening oncologic emergency associated with fatal complications including arrhythmia. The epidemiology and mortality outcomes of arrhythmia in TLS are scarcely studied in the literature. Methods We used the National Inpatient Sample (NIS) to study the prevalence and outcome of arrhythmia in patients hospitalized with TLS (ICD‐9 code 277.88) from 2009 to 2014. Baseline characteristics, burden of arrhythmia, and pertinent outcomes were analyzed. Multivariable regression analysis was performed to identify the impact of underlying malignancy in predicting TLS‐related mortality. Results A total of 9034 cases of arrhythmia among 37 861 TLS patients were identified. More than half of the arrhythmia cases (67%) were found among white old (>65) males admitted to large bed size and urban teaching hospitals. Arrhythmic cohort showed higher frequency of comorbidities such as fluid‐electrolyte disturbances, hypertension, congestive heart failure, renal failure, dyslipidemia, diabetes, pulmonary circulatory disorders, chronic pulmonary disease, coagulopathy, and deficiency anemia. The most common malignancies were leukemia, lymphoma, metastatic tumor, and solid tumor without metastasis. We found significantly higher odds of in‐hospital mortality among patients with TLS compared to general inpatient population on unadjusted (OR 9.69, 95% CI: 9.27‐10.13, P

Background & Aims: The protective intestinal mucosal barrier consists of multiple elements including mucus and epithelial layers and immune defense; nonetheless, barrier dysfunction is common in various disorders. The imprinted and developmentally regulated long noncoding RNA H19 is involved in many cell processes and diseases. Here, we investigated the role of H19 in regulating Paneth and goblet cells and autophagy, and its impact on intestinal barrier dysfunction induced by septic stress. Methods: Studies were conducted in H19-deficient (H19-/-) mice, mucosal tissues from patients with sepsis, primary enterocytes, and Caco-2 cells. Septic stress was induced by cecal ligation and puncture (CLP), and gut permeability was detected by tracer fluorescein isothiocyanate–dextran assays. The function of Paneth and goblet cells was examined by immunostaining for lysozyme and mucin 2, respectively, and autophagy was examined by microtubule-associated proteins 1A/1B light chain 3 II immunostaining and Western blot analysis. Intestinal organoids were isolated from H19-/- and control littermate mice and treated with lipopolysaccharide (LPS). Results: Intestinal mucosal tissues in mice 24 hours after exposure to CLP and in patients with sepsis showed high H19 levels, associated with intestinal barrier dysfunction. Targeted deletion of the H19 gene in mice enhanced the function of Paneth and goblet cells and promoted autophagy in the small intestinal mucosa. Knockout of H19 protected Paneth and goblet cells against septic stress, preserved autophagy activation, and promoted gut barrier function after exposure to CLP. Compared with organoids from control littermate mice, intestinal organoids isolated from H19-/- mice had increased numbers of lysozyme- and mucin 2–positive cells and showed increased tolerance to LPS. Conversely, ectopic overexpression of H19 in cultured intestinal epithelial cells prevented rapamycin-induced autophagy and abolished the rapamycin-induced protection of the epithelial barrier against LPS. Conclusions: In investigations of mice, human tissues, primary organoids, and intestinal epithelial cells, we found that increased H19 inhibited the function of Paneth and goblet cells and suppressed autophagy, thus potentially contributing to barrier dysfunction in intestinal pathologies.

Background & Aims: The mammalian intestinal epithelium is a rapidly self-renewing tissue in the body, and its homeostasis is tightly regulated via well-controlled mechanisms. The RNA-binding protein HuR is essential for maintaining gut epithelial integrity, and targeted deletion of HuR in intestinal epithelial cells (IECs) disrupts mucosal regeneration and delays repair after injury. Here, we defined the role of HuR in regulating subcellular distribution of small guanosine triphosphatase Rac1 and investigated the implication of nucleophosmin (NPM) as a molecular chaperone in this process. Methods: Studies were conducted in intestinal epithelial tissue-specific HuR knockout (IE-HuR-/-) mice and cultured IEC-6 cells, derived from rat small intestinal crypts. Functions of HuR and NPM in vitro were investigated via their gene silencing and overexpression. Results: The abundance of cytoplasmic Rac1 in the small intestinal mucosa increased significantly in IE-HuR-/- mice, although HuR deletion did not alter total Rac1 levels. HuR silencing in cultured IECs also increased the cytoplasmic Rac1 levels, without an effect on whole-cell Rac1 content. In addition, HuR deficiency in the intestinal epithelium decreased the levels of NPM in IE-HuR-/- mice and cultured IECs. NPM physically interacted with Rac1 and formed the NPM/Rac1 complex. NPM silencing decreased the NPM/Rac1 association and inhibited nuclear accumulation of Rac1, along with an increase in cytoplasmic abundances of Rac1. In contrast, ectopically expressed NPM enhanced Rac1 nuclear translocation and restored Rac1 subcellular localization to near normal in HuR-deficient cells. Conclusions: These results indicate that HuR regulates Rac1 nucleocytoplasmic shuttling in the intestinal epithelium by altering NPM expression. Keywords: RNA-Binding Proteins, GTP-Binding Proteins, IECs, Nucleocytoplasmic Shuttling, Conditional Deletion

Paneth cells are specialized intestinal epithelial cells that are located at the base of small intestinal crypts and play a vital role in preserving the gut epithelium homeostasis. Paneth cells act as a safeguard from bacterial translocation across the epithelium and constitute the niche for intestinal stem cells in the small intestine by providing multiple niche signals. Recently, Paneth cells have become the focal point of investigations defining the mechanisms underlying the epithelium-microbiome interactions and pathogenesis of chronic gut mucosal inflammation and bacterial infection. Function of Paneth cells is tightly regulated by numerous factors at different levels, while Paneth cell defects have been widely documented in various gut mucosal diseases in humans. The post-transcription events, specific change in mRNA stability and translation by RNA-binding proteins (RBPs) and noncoding RNAs (ncRNAs) are implicated in many aspects of gut mucosal physiology by modulating Paneth cell function. Deregulation of RBPs and ncRNAs and subsequent Paneth cell defects are identified as crucial elements of gut mucosal pathologies. Here, we overview the posttranscriptional regulation of Paneth cells by RBPs and ncRNAs, with a particular focus on the increasing evidence of RBP HuR and long ncRNA H19 in this process. We also discuss the involvement of Paneth cell dysfunction in altered susceptibility of the intestinal epithelium to chronic inflammation and bacterial infection following disrupted expression of HuR and H19.

OBJECTIVES/SPECIFIC AIMS: Computed tomography (CT) enables 3-dimensional (3D) visualization of cortical bone structures with high spatial resolution, and thus has been the gold-standard method for evaluation and diagnosis of craniofacial skeletal pathologies. However, ionizing radiation and, in particular, repeated scanning for presurgery and postsurgery assessments, is of concern when applied to infants and young children. Recent advances in solid-state MRI allow the capture of the short-T2 signals in cortical bone while suppressing the signal from soft-tissue protons having T2 relaxation time 1–2 orders of magnitude longer (50–100 ms). One approach, a dual-radiofrequency (RF) pulse and ultrashort echo time (UTE) imaging based method, exploits different sensitivities of bone and soft tissue to different RF pulse widths and TEs. This study aims to demonstrate the feasibility of producing 3D renderings of the human skull and visualization of cranial sutures using the bone-selective MRI technique in comparison to CT. METHODS/STUDY POPULATION: Imaging technique: Two RF pulses differing in duration and amplitude are alternately applied in successive repetition time (TR) along the pulse train. Within each TR, 2 echoes are acquired. Acquisition of the first echo starts at the ramp-up of the encoding gradient (TE1), allowing for capture of signals with very short lifetimes (bone), while that of the second starts after a longer delay (TE2). In total, 4 echoes are obtained: ECHO11 (RF1TE1), ECHO12 (RF1TE2), ECHO21 (RF2TE1), and ECHO22 (RF2TE2). During reconstruction, ECHO11 is combined with ECHO21 and ECHO12 is combined with ECHO22, resulting in 2 images. The subtraction of these 2 images yields an enhanced bone contrast. Data acquisition/processing: The pulse sequence described above was applied for MR imaging of a human cadaveric skull and 2 adult human subjects in vivo, at 3T field strength (Siemens Prisma, Erlangen, Germany). Imaging parameters: TR/TE1/TE2=7/0.06/2.46 ms, RF1/RF2 durations=40/520 μs, flip angle=12°, matrix size=2563, field of view=2803 mm3, voxel size=1.1 mm isotropic, number of radial spokes=25,000, and scan time=6 minutes. Segmentation of bone voxels was performed using ITK-SNAP in a semi-automatic fashion, leading to 3D renderings of the skull. For comparison, a CT scan was also performed in the human cadaveric skull with 1 mm isotropic resolution. Validation: The biometric accuracy was assessed by measuring eight anatomic distances: (1) Maximum craniocaudal aperture of the right orbit. (2) Maximum craniocaudal aperture of the left orbit. (3) Maximum height of the mandible from chin point in the midline. (4) Maximum cranial length (5) Maximum cranial width. (6) Maximum height of piriform aperture. (7) Distance between lateral most aspect of mandibular condyles. (8) Distance between lateral most aspect of posterior hard palate in both CT- and MRI-based 3D renderings of the human cadaveric skull using Mimics software (Materialise®, Ghent, Belgium). These distances were compared with those directly measured on the cadaveric skull. RESULTS/ANTICIPATED RESULTS: Compares CT with the proposed MRI method on cadaveric human skull images, along with corresponding 3D renderings. Compared with CT, the 3D rendered images maintain most features over the entire head (e.g., zygomatic arch), except for appearance of some artifacts in the mandibular region. In vivo head images in 2 adult subjects: axial magnitude images and 3D rendering. In the axial images, bone voxels as well as the inner table of the cranium are clearly visualized, and cranial and spinal bone structures are well depicted in the 3D renderings. Some voxels were erroneously included or excluded in the renderings. The mean difference in measurements of the 8 anatomic distances was 6, 4, and 2 mm when comparing MRI Versus CT, MRI Versus in situ, and CT Versus in situ, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Bone proton magnetization exhibits a substantial level of signal decay during the relatively long duration of RF2 due to its very short T2 relaxation time. In contrast, soft-tissue retains nearly the same level of signal intensities over all echoes. Thus, subtraction of ECHO22 from ECHO11, when compared with the difference between ECHO11 and ECHO12, enhances bone contrast from soft tissue. The proposed, dual-RF dual-echo 3D UTE imaging technique produces isotropic high-resolution bone-specified images in the whole head within a clinically feasible imaging time (6 min), leading to clear visualization of craniofacial skeletal structures. These are key components necessary for translation to the clinical setting. Optimization of postprocessing for more realistic 3D renderings and thus accurate anatomic measurements is currently being implemented. The proposed method’s potential as a nonradiative alternative to CT will then be thoroughly evaluated in pediatric patients.

The title compound, C26H18N4O5, can be regarded as an extended ether with two terminal nitro groups. The two aryl rings bonded to the central O atom form a dihedral angle of 75.72 (6)°, and the terminal nitro groups are slightly twisted [by 6.4 (2) and 3.3 (3)°] from the benzene rings to which they are attached. The crystal packing exhibits weak intermolecular C—H...O hydrogen bonds and π–π interactions [centroid–centroid distances = 3.794 (3) Å].

Paneth cells at the bottom of small intestinal crypts secrete antimicrobial peptides, enzymes, and growth factors and contribute to pathogen clearance and maintenance of the stem cell niche. Loss of Paneth cells and their dysfunction occur commonly in various pathologies, but the mechanism underlying the control of Paneth cell function remains largely unknown. Here, we identified microRNA-195 (miR-195) as a repressor of Paneth cell development and activity by altering SOX9 translation via interaction with RNA-binding protein HuR. Tissue-specific transgenic expression of miR-195 (miR195-Tg) in the intestinal epithelium decreased the levels of mucosal SOX9 and reduced the numbers of lysozyme-positive (Paneth) cells in mice. Ectopically expressed SOX9 in the intestinal organoids derived from miR-195-Tg mice restored Paneth cell development ex vivo. miR-195 did not bind to Sox9 mRNA but it directly interacted with HuR and prevented HuR binding to Sox9 mRNA, thus inhibiting SOX9 translation. Intestinal mucosa from mice that harbored both Sox9 transgene and ablation of the HuR locus exhibited lower levels of SOX9 protein and Paneth cell numbers than those observed in miR-195-Tg mice. Inhibition of miR-195 activity by its specific antagomir improved Paneth cell function in HuR-deficient intestinal organoids. These results indicate that interaction of miR-195 with HuR regulates Paneth cell function by altering SOX9 translation in the small intestinal epithelium. NEW & NOTEWORTHY: Our results indicate that intestinal epithelial tissue-specific transgenic miR-195 expression decreases the levels of SOX9 expression, along with reduced numbers of Paneth cells. Ectopically expressed SOX9 in the intestinal organoids derived from miR-195-Tg mice restores Paneth cell development ex vivo. miR-195 inhibits SOX9 translation by preventing binding of HuR to Sox9 mRNA. These findings suggest that interaction between miR-195 and HuR controls Paneth cell function via SOX9 in the intestinal epithelium. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to investigate clinical characteristics and glaucoma progression in eyes with disc hemorrhage (DH) in the region of peripapillary atrophy (PPA) or DH in temporal region among glaucoma patients with myopia. One hundred ninety-six eyes of 196 glaucoma patients with myopia who were observed at least 4 years and had more than six visual field (VF) tests were included. Eyes with DHs located in the optic disc region at the superotemporal or inferotemporal locations were defined as typical DH. PPA area, disc ovality ratio, and disc torsion were measured. Length of γ-zone PPA, distance from disc edge to fovea, angle of scleral bending were measured using optical coherence tomography. Comparison of baseline characteristics between eyes with and without DH in PPA/DH in temporal region showed similar axial length (26.95 ± 1.60 mm; 26.82 ± 1.07 mm). γ-zone PPA was longer and angle of scleral bending was larger in eyes with DH in PPA/DH in temporal region (both p ≤ 0.001). Longer γ-zone PPA (β = 1.001; p = 0.018) and larger angle of scleral bending (β = 1.033; p = 0.008) were associated with presence of DH in PPA/DH in temporal region using logistic regression analysis. Eyes with DH in PPA/DH in temporal region had a smaller mean deviation slope of VF, a larger disc ovality ratio, a longer γ-zone PPA, and a larger PPA area when compared to those of eyes typical DH. VF progression was associated with absence of DH in PPA/DH in temporal region (p = 0.030) and larger angle of scleral bending (p = 0.019) using Cox proportional hazards model. DH in PPA/DH in temporal region was associated with stretching and deformation of sclera that may be result from myopic changes. Associated factors with VF progression was the degree of scleral deformation, not the presence of DH in PPA/DH in temporal region, showing that DH related to scleral deformation may possess clinical significance in glaucoma with myopia.

Abstract Background Astragali radix (AR) is one of the most widely used traditional Chinese herbal medicines. It exhibits diverse biological activities, including immunomodulatory and anti-inflammatory properties; however, some of its activities have only been demonstrated in vitro. Objective To examine the effects of orally administered AR extract on immune cells and the intestine under physiological conditions, which bridges the gap between previously observed in vitro outcomes and in vivo results. Methods AR extract was prepared by hot water extraction. Three separate animal experiments were conducted to isolate macrophages, splenocytes, and the small intestine epithelium. For the macrophage preparation experiment, an intraperitoneal injection of sterile thioglycolate was administered. The mice received oral AR extract at doses of 0.1, 0.5, or 2.5 g/kg for ten days. At the end of each experiment, cells or tissues were isolated. A portion of macrophages and splenocytes were analyzed for the phenotypic changes. The remaining cells were cultured and stimulated with lipopolysaccharide (LPS) or mitogen ex vivo to assess activation status, proliferation, and cytokine production. Samples of the intestine were subjected to real-time RT-PCR. Results Peritoneal macrophages from AR-treated mice exhibited increased expression of scavenger receptors, including SRA and CD36. Stimulation of these macrophages ex vivo with LPS selectively modulated the inflammatory response, including reduced expression of the costimulatory molecules CD40 and CD86, which are important for T cell responses, without affecting TNF-α and IL-6 production. Splenocytes from AR-treated mice exhibited a dose-dependent increase in CD4 and CD8 T cells; however, stimulation with mitogen decreased T cell proliferation and reduced IFN-γ production, which is essential for macrophage activation. An analysis of the small intestinal epithelium revealed an attenuated antimicrobial response, including reduced IgA content in the lumen and decreased expression of mucin-2 and polymeric Ig receptor genes. Conclusion The response of immune cells following oral treatment with AR extract did not replicate the previously documented in vitro findings. Immune cells and intestinal epithelium from mice administered oral AR extract exhibited a selective anti-inflammatory phenotype. The overall findings indicate that the systemic effects after oral administration of AR extract include reduced sensitivity to inflammatory insults.

Abstract The global industrial development and increase in the number of transportation vehicles, such as automobiles and ships, have led to a steady increase in the issues related to greenhouse gas emissions. NO2 is a greenhouse gas emitted in large quantities from automobiles and factories, and its emission is unavoidable in the modern world. Therefore, a sensor capable of precise detection of NO2 is required. The most commonly reported types of NO2 sensors are those based on metal oxides. However, their operation at room temperature is impossible owing to their high-temperature operating characteristics, and therefore, a heater must be designed inside or installed outside the sensor for heating. Meanwhile, NO2 sensors based on PbS quantum dots (QDs) are advantageous as they can operate at room temperature and can be easily manufactured through a solution process rather than a complicated semiconductor process. Herein, a NO2 sensor was fabricated by doping PbS QDs with poly(3-hexylthiophene) (P3HT). The as-developed sensor exhibited high responsivity to 100–0.4-ppm NO2 gas with a resolution of 200 ppb owing to the stability of the thin film and high hole mobility of P3HT.

Objectives. FDXR encodes mitochondrial ferredoxin reductase, which is associated with auditory neuropathy spectrum disorder (ANSD) and optic atrophy. To date, only two studies have described FDXR-related hearing loss. The auditory rehabilitation outcomes of this disease entity have not been investigated, and the pathophysiological mechanisms remain incompletely understood. Here we report a hearing-impaired individual with co-segregation of the FDXR variant and post-synaptic type ANSD, who underwent cochlear implantation (CI) with favorable outcomes. We suggest a possible pathophysiological mechanism of adult-onset ANSD involving mitochondrial dysfunction. Methods. A 35-year-old woman was ascertained to have ANSD. Exome sequencing identified the genetic cause of hearing loss, and a functional study measuring mitochondrial activity was performed to provide molecular evidence of pathophysiology. Expression of FDXR in the mouse cochlea was evaluated by immunohistochemistry. Intraoperatively, electrically evoked compound action potential (ECAP) responses were measured, and the mapping parameters were adjusted accordingly. Audiological outcomes were monitored for over 1 year. Results. In lymphoblastoid cell lines (LCLs) carrying a novel FDXR variant, decreased ATP levels, reduced mitochondrial membrane potential, and increased reactive oxygen species levels were observed compared to control LCLs. These dysfunctions were restored by administering mitochondria isolated from umbilical cord mesenchymal stem cells, confirming the pathogenic potential of this variant via mitochondrial dysfunction. Partial ECAP responses during CI and FDXR expression in the mouse cochlea indicate that FDXR-related ANSD is post-synaptic. As a result of increasing the pulse width during mapping, the patient’s CI outcomes showed significant improvement over 1-year post-CI. Conclusion. A novel FDXR variant associated with mitochondrial dysfunction and post-synaptic ANSD was first identified in a Korean individual. Additionally, 1-year post-CI outcomes were reported for the first time in the literature. Excellent audiologic results were obtained, and our results reiterate the correlation between genotype and CI outcomes in ANSD.

Background/Aims There is limited knowledge regarding the management of duodenal subepithelial lesions (SELs) owing to a lack of understanding of their natural course. This study aimed to assess the natural course of asymptomatic duodenal SELs and provide management recommendations. Methods Patients diagnosed with duodenal SELs and followed up for a minimum of 6 months were retrospectively investigated. Results Among the 443,533 patients who underwent esophagogastroduodenoscopy between 2008 and 2020, duodenal SELs were identified in 0.39% (1,713 patients). Among them, 396 duodenal SELs were monitored for a median period of 72.5 months (interquartile range, 37.7–111.3 mo). Of them, 16 SELs (4.0%) showed substantial changes in size or morphology at a median follow-up of 35.1 months (interquartile range, 21.7–51.4 mo). Of these SELs with substantial changes, tissues of two SELs were acquired using endoscopic ultrasound-guided fine needle aspiration biopsy: one was a lipoma and the other was non-diagnostic. Three SELs were surgically or endoscopically removed; two were diagnosed as gastrointestinal stromal tumors, and one was a lipoma. An initial size of 20 mm or larger was associated with substantial changes during follow-up (p = 0.016). Conclusions While the majority of duodenal SELs may not exhibit substantial interval changes, regular follow-up with endoscopy may be necessary for cases with an initial size of 20 mm or larger, considering a possibility of malignancy.

Ulmus davidiana has been used as food or medicine in oriental due to its safety, including its roots, bark, and fruits. The roots and bark of Ulmus were used as a diuretic and for treatment due to their anti-cancer, antioxidant, and anti-inflammatory effects. Ulmus species are known to contain flavan-3-ols as their main component. In previous research the presence of (+)-catechin 5-O-β-D-apiofuranoside was isolated from the roots of Ulmus davidiana, and (+)-catechin 7-O-β-D-xylopyranoside was confirmed in the bark Ulmus Americana, and the presence of catechin 7-O-β-D apiofuranoside in the stems and bark of Ulmus davidiana var. japonica. The catechin-glycosides of flavan-3-ols have various effects, including antiulcer properties, and have also been used as analgesics. Additionally, chemotaxonomy studies of the Ulmus species have been reported. However, the chemotaxonomy of Ulmus species native to Asia has not been reported. In this study, we report the screening of catechin 7-O-beta-D apiofuranoside from various Ulmus species native to Asia. We confirmed the presence of catechin 7-O-β-D-apiofuranoside in a total of 22 Ulmus samples, including 18 Ulmus species native to China, and 1 sample each from Mongolian, Nicaragua, Vietnam, and Korea through HPLC and LC-MS/MS analysis. We also confirmed the content of the indicator materials. Therefore, the potential of using native Ulmus species from Korea as a natural material has been confirmed.

Background/Aims To overcome the technical limitations of classic endoscopic resection for gastric gastrointestinal stromal tumors (GISTs), various methods have been developed. In this study, we examined the role and feasibility of clip-and-cut procedures (clip-and-cut endoscopic full-thickness resection [cc-EFTR]) for gastric GISTs. Methods Medical records of 83 patients diagnosed with GISTs after endoscopic resection between 2005 and 2021 were retrospectively reviewed. Moreover, clinical characteristics and outcomes were analyzed. Results Endoscopic submucosal dissection (ESD) and cc-EFTR were performed in 51 and 32 patients, respectively. The GISTs were detected in the upper third of the stomach for ESD (52.9%) and cc-EFTR (90.6%). Within the cc-EFTR group, a majority of GISTs were located in the deep muscularis propria or serosal layer, accounting for 96.9%, as opposed to those in the ESD group (45.1%). The R0 resection rates were 51.0% and 84.4% in the ESD and cc-EFTR groups, respectively. Seven (8.4%) patients required surgical treatment (six patients underwent ESD and one underwent cc-EFTR,) due to residual tumor (n=5) and post-procedure adverse events (n=2). Patients undergoing R0 or R1 resection did not experience recurrence during a median 14-month follow-up period, except for one patient in the ESD group. Conclusions cc-EFTR displayed a high R0 resection rate; therefore, it is a safe and effective therapeutic option for small gastric GISTs.

Background Helicobacter pylori infection, prevalent in more than half of the global population, is associated with various gastrointestinal diseases, including peptic ulcers and gastric cancer. The effectiveness of early diagnosis and treatment in preventing gastric cancer highlights the need for improved diagnostic methods. This study aimed to develop a simple scoring system based on endoscopic findings to predict H. pylori infection. Methods A retrospective analysis was conducted on 1,007 patients who underwent upper gastrointestinal endoscopy at Asan Medical Center from January 2019 to December 2021. Exclusion criteria included prior H. pylori treatment, gastric surgery, or gastric malignancies. Diagnostic techniques included rapid urease and 13C-urea breath tests, H. pylori culture, and assessment of endoscopic features following the Kyoto gastritis classification. A new scoring system based on endoscopic findings including regular arrangement of collecting venules (RAC), nodularity, and diffuse or spotty redness was developed for predicting H. pylori infection, utilizing logistic regression analysis in the development set. Results The scoring system demonstrated high predictive accuracy for H. pylori infection in the validation set. Scores of 2 and 3 were associated with 96% and 99% infection risk, respectively. Additionally, there was a higher prevalence of diffuse redness and sticky mucus in cases where the initial H. pylori eradication treatment failed. Conclusions Our scoring system showed potential for improving diagnostic accuracy in H. pylori infection. H. pylori testing should be considered upon spotty redness, diffuse redness, nodularity, and RAC absence on endoscopic findings as determined by the predictive scoring system.

Vault RNAs (vtRNAs) are small noncoding RNAs and highly expressed in many eukaryotes. Here, we identified vtRNA2‐1 as a novel regulator of the intestinal barrier via interaction with RNA‐binding protein HuR. Intestinal mucosal tissues from patients with inflammatory bowel diseases and from mice with colitis or sepsis express increased levels of vtRNAs relative to controls. Ectopically expressed vtRNA2‐1 decreases the levels of intercellular junction (IJ) proteins claudin 1, occludin, and E‐cadherin and causes intestinal epithelial barrier dysfunction in vitro, whereas vtRNA2‐1 silencing promotes barrier function. Increased vtRNA2‐1 also decreases IJs in intestinal organoid, inhibits epithelial renewal, and causes Paneth cell defects ex vivo. Elevating the levels of tissue vtRNA2‐1 in the intestinal mucosa increases the vulnerability of the gut barrier to septic stress in mice. vtRNA2‐1 interacts with HuR and prevents HuR binding to claudin 1 and occludin mRNAs, thus decreasing their translation. These results indicate that vtRNA2‐1 impairs intestinal barrier function by repressing HuR‐facilitated translation of claudin 1 and occludin. Synopsis: Vault RNAs (vtRNAs) are small noncoding RNAs, and their levels increase in intestinal mucosa from patients with IBD. vtRNA2‐1 disrupts intestinal epithelial barrier function by decreasing intercellular junctions via interaction with HuR. vtRNA2‐1 inhibits expression of claudin 1, occludin, and E‐cadherin posttranscriptionally.vtRNA2‐1 impairs intestinal epithelial renewal and causes Paneth cell defects ex vivo.Elevating tissue vtRNA2‐1 levels increases vulnerability of gut barrier to septic stress in mice.vtRNA2‐1 interacts with HuR and prevents HuR binding to mRNAs. [ABSTRACT FROM AUTHOR]

Abstract Many pathological conditions lead to defects in intestinal epithelial integrity and loss of barrier function; Sphingosine‐1‐phosphate (S1P) has been shown to augment intestinal barrier integrity, though the exact mechanisms are not completely understood. We have previously shown that overexpression of Sphingosine Kinase 1 (SphK1), the rate limiting enzyme for S1P synthesis, significantly increased S1P production and cell proliferation. Here we show that microRNA 495 (miR‐495) upregulation led to decreased levels of SphK1 resultant from a direct effect at the SphK1 mRNA. Increasing expression of miR‐495 in intestinal epithelial cells resulted in decreased proliferation and increased susceptibility to apoptosis. Transgenic expression of miR‐495 inhibited mucosal growth, as well as decreased proliferation in the crypts. The intestinal villi also expressed decreased levels of barrier proteins and exaggerated damage upon exposure to cecal ligation‐puncture. These results implicate miR‐495 as a critical negative regulator of intestinal epithelial protection and proliferation through direct regulation of SphK1, the rate limiting enzyme critical for production of S1P.

Background: Sasanlimab (PF-06801591), a humanized immunoglobulin G4 monoclonal antibody, binds to programmed cell death protein-1 (PD-1), preventing ligand (PD-L1) interaction. Objectives: To evaluate pharmacokinetics (PK), safety, tolerability, and efficacy of two subcutaneous sasanlimab dosing regimens. Design: An open-label study consisting of phases Ib and II. Phase Ib: non-randomized, dose escalation, and expansion study in Asian participants with advanced malignancies. Phase II: conducted globally in participants with non-small-cell lung cancer with PD-L1 positive or PD-L1 status unknown tumors; participants were randomized 1:2 to receive subcutaneous sasanlimab 300 mg once every 4 weeks (300 mg-Q4W) or 600 mg once every 6 weeks (600 mg-Q6W). Methods: Primary endpoint in phase Ib: dose-limiting toxicity (DLT) occurring in first treatment cycle; in phase II: C trough and AUC. Results: A total of 155 participants (phase Ib, n = 34; phase II, n = 121) received sasanlimab. Phase Ib: no DLT reported. Phase II: ratio of adjusted geometric mean for AUC tau was 231.2 (90% CI, 190.1–281.2) and C trough was 111.5 (90% CI, 86.3–144.0) following 600 mg-Q6W (test) versus 300 mg-Q4W (reference). Phase Ib: grade 3 treatment-related adverse events (TRAEs) occurred in 1/4 (25%) and 3/12 (25%) participants treated in 300 mg-Q4W dose escalation and expansion cohorts, respectively. Phase II: grade 3 TRAEs occurred in 3/41 (7.3%) and 3/80 (3.8%) participants treated with 300 mg-Q4W and 600 mg-Q6W, respectively; no grade 4/5 TRAEs. Phase II: confirmed objective response was observed in 11/41 (26.8% (95% CI, 14.2–42.9)) and 12/80 (15.0% (95% CI, 8.0–24.7)) participants treated with 300 mg-Q4W and 600 mg-Q6W, respectively. Conclusions: Phase Ib regimens were considered safe with no DLTs reported. In phase II, 600 mg-Q6W regimen criteria were met for AUC tau and C trough metrics to support PK-based extrapolation of efficacy of alternative regimen. Regimens were well tolerated, showing anti-tumor activity in participants with advanced solid tumors. Administration of sasanlimab at a dose of 600 mg-Q6W subcutaneously may serve as a convenient alternative to 300 mg-Q4W administration. Trial registration: NCT04181788 (ClinicalTrials.gov); 2019-003818-14 (EudraCT).

Background Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), serve as valuable prognostic indicators in various cancers. This multicenter, retrospective cohort study assessed the treatment outcomes of lenvatinib in 71 patients with radioactive iodine (RAI)-refractory thyroid cancer, considering the baseline inflammatory biomarkers. Methods This study retrospectively included patients from five tertiary hospitals in Korea whose complete blood counts were available before lenvatinib treatment. Progression-free survival (PFS) and overall survival (OS) were evaluated based on the median value of inflammatory biomarkers. Results No significant differences in baseline characteristics were observed among patients grouped according to the inflammatory biomarkers, except for older patients with a higher-than-median NLR (≥2) compared to their counterparts with a lower NLR (P= 0.01). Patients with a higher-than-median NLR had significantly shorter PFS (P=0.02) and OS (P=0.017) than those with a lower NLR. In multivariate analysis, a higher-than-median NLR was significantly associated with poor OS (hazard ratio, 3.0; 95% confidence interval, 1.24 to 7.29; P=0.015). However, neither the LMR nor the PLR was associated with PFS. A higher-than-median LMR (≥3.9) was significantly associated with prolonged OS compared to a lower LMR (P=0.036). In contrast, a higher-than-median PLR (≥142.1) was associated with shorter OS compared to a lower PLR (P=0.039). Conclusion Baseline inflammatory biomarkers can serve as predictive indicators of PFS and OS in patients with RAI-refractory thyroid cancer treated with lenvatinib.

Background/Aims: Peroral cholangioscopy (POC) has been used to assess intrahepatic duct (IHD) lesions but with a limited role. A new multibending (MB) ultraslim endoscope has been designed to improve POC performance. We evaluated the usefulness of POC using the MB ultraslim endoscope for the management of IHD lesions. Methods : Between March 2017 and March 2020, 22 patients underwent direct POC using the MB ultraslim endoscope for IHD lesions documented by previous imaging or cholangiopancreatography. The primary outcome was technical success of POC, and secondary outcomes were technical success of POC-guided interventions, median procedure time, and POC-related adverse events. Results : The technical success rate for POC using the MB ultraslim endoscope for IHD lesions was 95.5% (21/22). Free-hand insertion was successful in 95.2% (20/21). The overall technical success rate for POC-guided intervention was 100% (21/21), including nine diagnostic and 12 therapeutic procedures (eight direct stone removal and four intraductal lithotripsies). The median procedure time was 29 minutes (range, 9 to 79 minutes). There were no procedure-related adverse events. Conclusion : s: Direct POC using the MB ultraslim endoscope allows direct visualization of IHD lesions and may be useful for diagnosis and therapeutic management in selected patients.

Background : Recent lifestyle changes have increased the prevalence of dyslipidemia in Korea. Young men are known to have a low awareness of dyslipidemia and a lack of motivation to maintain their weight. However, the association between weight change and dyslipidemia in young adults has not been thoroughly examined. Methods : Data from the Armed Forces Medical Command Defense Medical Information System database were used. In this study, 15,068 soldiers who underwent private and corporal health examinations between May 2020 and April 2022 were included. The difference in weights between the two different health examinations was used to quantify weight change. Four components of the lipid profile were used to assess dyslipidemia during the corporal health examination. Results : After adjusting for relevant covariates, weight gain was associated with increased risk of dyslipidemia (adjusted odds ratio [OR], 1.38 [95% confidence interval, CI, 1.15 to 1.64] for the 5% to 10% weight gain group; and OR, 2.02 [95% CI, 1.59 to 2.55] for the ≥10% weight gain group), whereas weight loss was associated with decreased risk (adjusted OR, 0.82 [95% CI, 0.68 to 0.98] for the 5% to 10% weight loss group; and OR, 0.38 [95% CI, 0.27 to 0.53] for the ≥10% weight loss group). In subgroup analysis based on the participants’ baseline body mass index, smoking status, regular exercise habits, and hypertension status, there were no significant differences between the subgroups. Conclusion : Weight change was associated with dyslipidemia in Korean male soldiers. The findings suggest that limiting weight gain in young adults by encouraging a healthy lifestyle may help prevent dyslipidemia.

Abstract In order to explore the spectrum of mitochondrial DNA (mtDNA) mutations in Korean patients with Leber's hereditary optic neuropathy (LHON), we investigated the spectrum of mtDNA mutations in 145 Korean probands confirmed with the diagnosis of LHON. Total genomic DNA was isolated from the peripheral blood leukocytes of the patients with suspected LHON, and mtDNA mutations were identified by direct sequencing. Analysis of mtDNA mutations revealed seven primary LHON mutations including the nucleotide positions (nps) 11778A (101 probands, 69.2%), 14484C (31 probands, 21.2%), 3460A (5 probands, 3.4%), and G3635A, G3733A, C4171A, and G13051A mutations in one proband each. In addition, two provisional mtDNA mutations at nps T3472C, and G13259A were each found in one proband, respectively. Another provisional mtDNA mutation at np T3394C was found in two probands. In conclusion, the spectrum of mtDNA mutations in Korean patients with LHON may differ from other ethnicities, which is characterized by high prevalence of 11778A and 14484C mutations, and a low prevalence of the 3460A mutation.

Abstract Background Plant viruses cause economic losses by reducing the quantity and quality of major crops. This issue is a growing concern due to the expansion of global trade and climate change. In addition, the emergence of new pathogen strains increases the difficulty of controlling viral diseases. Effective management strategies are therefore needed. The control strategy for viral diseases relies primarily on non-chemical and cultural practices, as no commercial viricides are currently available. Some compounds have been identified as effective against certain viruses, but their use in the field is limited due to issues such as concentration, toxicity, and efficacy. Therefore, it is imperative to discover novel antiviral agents that address the existing challenges associated with the identified antiviral candidate compounds. Results In this study, we evaluated iodine-conjugated organic compounds mixed with sialic acid, whey, and blood meal for virus disease management against seven viruses that cause significant yield losses and economic damage to plants. The candidate compounds reduced virus accumulation and symptom development. Treatment with candidate compounds, A4 and A5, reduced viral RNA accumulation to about half that of those in the control group and showed reduced symptoms along with healthier growth. In addition, we performed transcriptome analysis of treatment with two viruses, which suggested that the mechanism of viral RNA replication inhibition might relate to plant defense systems based on phytohormone pathways. Conclusions This study demonstrated that treatments with naturally derived materials, such as iodine, nitrogen, and sialic acid-conjugated organic substances, may directly or indirectly impact the host plant's resistance to various virus infections. Moreover, our findings suggest that these natural candidate materials could be utilized for managing virus diseases in the field. Graphical Abstract

Abstract Achieving optimal camouflage in an aquatic environment necessitates the ability to modulate transmittance in response to the surrounding obscurity and potential threats. This adaptation involves a dynamic transition from transparency to a deep-blue color, especially in low-light or dark situations. Such a strategy promotes a seamless assimilation with the surroundings, enabling the absorption of searchlights and, subsequently, diminishing the risk of detection by predators. Therefore, the presence of sophisticated mechanisms that facilitates stable and efficient control of transmittance is imperative, enabling smooth transition between transparent and deep-blue hues within the aquatic environment. This study presents nature-inspired programmable camouflage system that integrates an electrochromic display as the primary transmittance change element and a wireless base module for power and data transmission. Such technology offers a robust and flexible construction, ensuring stable operation as demonstrated through mechanical-fatigue experiments and quantitative simulation. A custom circuit and a power-control software package enable active control of multiple electrochromic displays while submerged in water.

We present a rare case of histiocytic sarcoma (HS) occurring in the foot of a 12-year-old male, initially misdiagnosed as localized tenosynovial giant cell tumor (TSGCT). HS is an exceptionally uncommon hematologic malignant neoplasm, with its occurrence in children and extranodal sites being even rarer. To our knowledge, this is the first reported case of extranodal HS in the foot, emphasizing comprehensive MRI findings. Initially, the patient was diagnosed with TSGCT based on histological results following surgical resection. However, after recurrence and subsequent surgical resection, histological and immunochemical analyses led to a revised diagnosis of HS. This report focuses on the MRI findings of HS, highlighting the distinctions from localized TSGCT. While both conditions share histopathological similarities, immunohistochemical tests are crucial for accurate diagnosis. The report underscores the importance of differentiating HS for appropriate treatment.

Abstract Over the past decade, numerous studies have highlighted the importance of acid sphingomyelinase (ASM) in disease treatment in humans. This enzyme functions primarily to generate ceramide, maintain the cellular membrane, and regulate cellular function. However, in the blood and brain of patients with neurological disorders, including major depression, ischemic stroke, amyotrophic lateral sclerosis, multiple sclerosis, and Alzheimer’s disease (AD), elevated ASM levels significantly suggest disease onset or progression. In these diseases, increased ASM is profoundly involved in neuronal death, abnormal autophagy, neuroinflammation, blood–brain barrier disruption, hippocampal neurogenesis loss, and immune cell dysfunction. Moreover, genetic and pharmacological inhibition of ASM can prevent or ameliorate various diseases. The therapeutic effects of ASM inhibition have prompted the urgent need to develop ASM inhibitors, and several ASM inhibitors have been identified. In this review, we summarize the current knowledge on the critical roles and mechanisms of ASM in brain cells and blood that are associated with different neuropathological features, especially those observed in AD. Furthermore, we elucidate the potential possibility and limitations of existing ASM-targeting drugs according to experimental studies in neurological disorder mouse models.

Abstract We conducted a prospective study to evaluate the efficacy of simulation-based education using a three-dimensional (3D)-printed schematic eye model in improving the retinoscopy refraction skills of medical students. A schematic eye model was printed using a fused deposition modeling-based 3D printer. Twenty medical students randomized into 3D (n = 10) and control (n = 10) groups received a 1-h lecture on the principles and methods of manifest refraction and were shown how to use the retinoscope and sciascope bars. The 3D group additionally attended a tutorial on the schematic eye. Both groups performed refractive examinations on four eyes of volunteer patients, and the results were recorded as a baseline. Instructor feedback and refraction practice was provided with the 3D group or with control group. To account for subject fatigue, patients spent no more than 8 min on the examination. After a 1-h break to allow for fatigue and familiarity, refraction tests were repeated on four randomly selected eyes of patients. Students’ refraction readings were compared with the autorefractor values using a spherical equivalent value and blur strength. All participants measured the time required to complete the refraction test and reported their subjective confidence in the results of each refraction test. Refractive errors before and after training did not differ between the control and 3D groups, with a significant improvement in errors observed in both groups (p = 0.005 and 0.008, respectively). The time to complete refraction before and after training did not differ between the two groups, both of which showed a significant reduction in time (p = 0.005 and 0.028, respectively). Pre- and post-training confidence scores for the accuracy of each refraction on a 10-point Likert scale were not significantly different. However, when comparing score changes between pre- and post-training, only the control group showed a significant increase in confidence (p = 0.005). Tests for the non-inferiority of refractive errors after training indicated that the 3D group was non-inferior to the control group. In conclusion, training in retinoscopy refraction skills using a 3D-printed eye model resulted in significant improvement in accuracy and speed compared to practice with real patients. Except for better confidence in the control group, schematic eye model training was not inferior to practice with real patients.

Abstract Rehabilitation improves symptoms, quality of life, and survival in patients with chronic respiratory or cardiovascular disease. We evaluated smartphone application-based rehabilitation programs for patients with chronic respiratory or cardiovascular diseases. This was a single-center prospective single arm study. Participants underwent smartphone application-based pulmonary or cardiac rehabilitation for 12 weeks. A total of 93 participants were recruited, and 75 visited after rehabilitation. Their median age was 67.0 (interquartile range, 60.0–70.8) years, and 60 (80.0%) were men. For patients with chronic respiratory disease (n = 41), VO2peak (median 13.7 to 15.4 ml/kg/min, P = 0.049), chronic obstructive pulmonary disease assessment test (median 14 to 6, P

Background Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS). Methods Studies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized. Results In the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%–10.8% and 16.0%–25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%–1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered. Conclusion AS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.