Repeated intrathecal injections of peripheral nerve-derived stem cell spheroids improve outcomes in a rat model of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide. However, existing treatments still face numerous clinical challenges. Building on our prior research showing peripheral nerve-derived stem cell (PNSC) spheroids with Schwann cell-like phenotypes can secrete neurotrophic factors to aid in neural tissue regeneration, we hypothesized that repeated intrathecal injections of PNSC spheroids would improve the delivery of neurotrophic factors, thereby facilitating the restoration of neurological function and brain tissue repair post-TBI. METHODS: We generated PNSC spheroids from human peripheral nerve tissue using suspension culture techniques. These spheroids were characterized using flow cytometry, immunofluorescence, and reverse-transcription polymerase chain reaction. The conditioned media were evaluated in SH-SY5Y and RAW264.7 cell lines to assess their effects on neurogenesis and inflammation. To simulate TBI, we established a controlled cortical impact (CCI) model in rats. The animals were administered intrathecal injections of PNSC spheroids on three occasions, with each injection spaced at a 3-day interval. Recovery of sensory and motor function was assessed using the modified neurological severity score (mNSS) and rotarod tests, while histological (hematoxylin and eosin, Luxol fast blue staining) and T2-weighted magnetic resonance imaging analyses, alongside immunofluorescence, were conducted to evaluate the recovery of neural structures and pathophysiology. RESULTS: PNSC spheroids expressed high levels of Schwann cell markers and neurotrophic factors, such as neurotrophin-3 and Ephrin B3. Their conditioned medium was found to promote neurite outgrowth, reduce reactive oxygen species-mediated cell death and inflammation, and influence M1-M2 macrophage polarization. In the CCI rat model, rats receiving repeated triple intrathecal injections of PNSC spheroids showed significant improvements in sensory and motor function, with considerable neural tissue recovery in damaged areas. Notably, this treatment promoted nerve regeneration, axon regrowth, and remyelination. It also reduced glial scar formation and inflammation, while encouraging angiogenesis. CONCLUSION: Our findings suggest that repeated intrathecal injections of PNSC spheroids can significantly enhance neural recovery after TBI. This effect is mediated by the diverse neurotrophic factors secreted by PNSC spheroids. Thus, the strategy of combining therapeutic cell delivery with multiple intrathecal injections holds promise as a novel clinical treatment for TBI recovery.

Assessing medication use patterns among patients with polycystic ovary syndrome at a tertiary care teaching hospital in South Korea: A retrospective study.

Polycystic ovary syndrome (PCOS) is a disease caused by excessive ovarian androgen secretion due to hypothalamic-pituitary-ovarian hormone abnormalities. We retrospectively investigated the treatment status of patients diagnosed with PCOS who visited a domestic tertiary hospital in order to analyze the use patterns and safety of drugs. Patients diagnosed with PCOS between July 2014 and September 2022 were examined, excluding patients younger than 13 years and those not receiving medication. Patients aged 21 years or younger were designated as the adolescent group and patients aged 22 years or older were designated as the adult group for comparative statistical analysis. The total number of patients was 212, including 105 adolescents (49.5%) and 107 adults (50.5%). Comorbidities were ovarian cyst in 20 (9.4%) patients, endometriosis in 19 (9%), diabetes in 14 (6.6%), thyroid dysfunction in 12 (5.7%), hypertension in 10 (4.7%), dyslipidemia in 10 (4.7%), and androgenic alopecia in 6 (2.8%). Symptoms were oligomenorrhea in 91 (42.9%) patients, amenorrhea in 72 (34%), hirsutism in 36 (17%), acne in 24 (11.3%), and infertility in 10 (4.7%). During the study period, 114 patients (53.8%) were prescribed medroxyprogesterone acetate (MPA), 66 (31.1%) were given oral contraceptives (specifically, ethinyl estradiol + drospirenone prescribed to 52 (24.5%)), and 17 (8%) were concurrently prescribed MPA and oral contraceptives. Forty-five (21.2%) patients changed prescriptions, with 10 (22.2%) switching due to side effects and 8 (17.8%) due to a therapeutic failure. A total of 5 patients (2.4%) discontinued the drug. Adverse drug reactions occurred in 15 patients (7.1%), with 5 being adolescents (4.8%) and 10 being adults (9.3%). MPA alone and ethinyl estradiol with drospirenone were the most prescribed medications for PCOS. Over the study, 45 patients changed prescriptions, 50 were lost to follow-up, and 5 adults discontinued medications.

Association between high-sensitivity C-reactive protein and renal function in Korean adults: A sex-specific analysis of Korea National Health and Nutrition Examination Survey 2015 to 2018 data.

This study aimed to investigate the association between high-sensitivity C-reactive protein (hs-CRP) levels, as a surrogate marker of systemic inflammation, and renal function among Korean adults grouped by age, sex, and body mass index. This study analyzed data obtained from the Korea National Health and Nutrition Examination Survey 2015 to 2018, a cross-sectional and nationally representative survey conducted by the Korean Centers for Disease Control and Prevention. Of the 22,451 subjects included in this study, 19,607 (87.3%) and 2844 (12.7%) had normal kidney function and incident chronic kidney disease, respectively. Reduced renal function was more frequently observed in subjects with high hs-CRP levels than in those with low hs-CRP levels (odds ratio [OR], 1.438; 95% confidence interval [CI], 1.234-1.674). In the group aged ≥ 65 years, the odds of reduced renal function were higher among subjects with a high hs-CRP level compared to those with a low hs-CRP level (OR, 1.528; 95% CI, 1.191-1.960). The association between hs-CRP level and renal function was observed only in women (OR, 2.485; 95% CI, 1.779-3.470) and further stratified by age and sex, the odds of reduced renal function were likely higher in women aged ≥ 65 years with a high hs-CRP level (OR, 2.338; 95% CI, 1.622-3.369). Moreover, reduced renal function was more observed in subjects aged ≥ 65 years and those with a body mass index < 25 kg/m2 (OR, 1.502; 95% CI, 1.087-2.075). This study showed that a high hs-CRP level likely contributes to the increased prevalence of reduced renal function. This association may aid the identification of individuals at high risk for reduced renal function, especially elderly women, in clinical or public health practice.

hsa-miR-CHA2, a novel microRNA, exhibits anticancer effects by suppressing cyclin E1 in human non-small cell lung cancer cells.

Despite considerable therapeutic advancements, the global survival rate for lung cancer patients remains poor, posing challenges in developing an effective treatment strategy. In many cases, microRNAs (miRNAs) exhibit abnormal expression levels in cancers, including lung cancer. Dysregulated miRNAs often play a crucial role in the development and progression of cancer. Therefore, understanding the mechanisms underlying aberrant miRNA expression during carcinogenesis may provide crucial clues to develop novel therapeutics. In this study, we identified and cloned a novel miRNA, hsa-miR-CHA2, which is abnormally downregulated in non-small cell lung cancer (NSCLC)-derived cell lines and tissues of patients with NSCLC. Furthermore, we found that hsa-miR-CHA2 regulates the post-transcriptional levels of Cyclin E1 (CCNE1) by binding to the 3'-UTR of CCNE1 mRNA. CCNE1, a cell cycle regulator involved in the G1/S transition, is often amplified in various cancers. Notably, hsa-miR-CHA2 overexpression led to the alteration of the Rb-E2F pathway, a significant signaling pathway in the cell cycle, by targeting CCNE1 in A549 and SK-LU-1 cells. Subsequently, we confirmed that hsa-miR-CHA2 induced G1-phase arrest and exhibited an anti-proliferative effect by targeting CCNE1. Moreover, in subcutaneous xenograft mouse models, intra-tumoral injection of polyplexed hsa-miR-CHA2 mimic suppressed tumor growth and development. In conclusion, hsa-miR-CHA2 exhibited an anticancer effect by targeting CCNE1 both in vitro and in vivo. These findings suggest the potential role of hsa-miR-CHA2 as an important regulator of cell proliferation in molecular-targeted therapy for NSCLC.

Establishment of an artificial urine model in vitro and rat or pig model in vivo to evaluate urinary crystal adherence.

The current study aimed to establish an experimental model in vitro and in vivo of urinary crystal deposition on the surface of ureteral stents, to evaluate the ability to prevent crystal adhesion. Non-treated ureteral stents were placed in artificial urine under various conditions in vitro. In vivo, ethylene glycol and hydroxyproline were administered orally to rats and pigs, and urinary crystals and urinary Ca were investigated by Inductively Coupled Plasma-Optical Emission Spectrometer. in vitro, during the 3- and 4-week immersion periods, more crystals adhered to the ureteral stent in artificial urine model 1 than the other artificial urine models (p < 0.01). Comparing the presence or absence of urea in the composition of the artificial urine, the artificial urine without urea showed less variability in pH change and more crystal adhesion (p < 0.05). Starting the experiment at pH 6.3 resulted in the highest amount of crystal adhesion to the ureteral stent (p < 0.05). In vivo, urinary crystals and urinary Ca increased in rat and pig experimental models. This experimental model in vitro and in vivo can be used to evaluate the ability to prevent crystal adhesion and deposition in the development of new ureteral stents to reduce ureteral stent-related side effects in patients.

Pathophysiological Roles of Ion Channels in Epidermal Cells, Immune Cells, and Sensory Neurons in Psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by the rapid abnormal growth of skin cells in the epidermis, driven by an overactive immune system. Consequently, a complex interplay among epidermal cells, immune cells, and sensory neurons contributes to the development and progression of psoriasis. In these cellular contexts, various ion channels, such as acetylcholine receptors, TRP channels, Ca2+ release-activated channels, chloride channels, and potassium channels, each serve specific functions to maintain the homeostasis of the skin. The dysregulation of ion channels plays a major role in the pathophysiology of psoriasis, affecting various aspects of epidermal cells, immune responses, and sensory neuron signaling. Impaired function of ion channels can lead to altered calcium signaling, inflammation, proliferation, and sensory signaling, all of which are central features of psoriasis. This overview summarizes the pathophysiological roles of ion channels in epidermal cells, immune cells, and sensory neurons during early and late psoriatic processes, thereby contributing to a deeper understanding of ion channel involvement in the interplay of psoriasis and making a crucial advance toward more precise and personalized approaches for psoriasis treatment.

Safety assessment and gastrointestinal retention of orally administered cerium oxide nanoparticles in rats.

Cerium oxide nanoparticles (CeO2 NPs, NM-212) are well-known for their catalytic properties and antioxidant potential, and have many applications in various industries, drug delivery, and cosmetic formulations. CeO2 NPs exhibit strong antimicrobial activity and can be used to efficiently remove pathogens from different environments. However, knowledge of the toxicological evaluation of CeO2 NPs is too limited to support their safe use. In this study, CeO2 NPs were orally administered to Sprague Dawley rats for 13 weeks at the doses of 0, 10, 100, and 1000 mg/kg bw/day, followed by a four week recovery period. The hematology values for the absolute and relative reticulocyte counts in male rats treated with 1000 mg/kg bw/day CeO2 NPs were lower than those in control rats. The clinical chemistry values for sodium and chloride in the treated male rat groups (100 and 1000 mg/kg/day) and total protein and calcium in the treated female rat groups (100 mg/kg/day) were higher than those in the control groups. However, these changes were not consistent in both sexes, and no abnormalities were found in the corresponding pathological findings. The results showed no adverse effects on any of the parameters assessed. CeO2 NPs accumulated in the jejunum, colon, and stomach wall of rats administered 1000 mg/kg CeO2 NPs for 90 days. However, these changes were not abnormal in the corresponding histopathological and immunohistochemical examinations. Therefore, 1000 mg/kg bw/day may be considered the "no observed adverse effect level" of CeO2 NPs (NM-212) in male and female SD rats under the present experimental conditions.

Stereotypic T cell receptor clonotypes in the thymus and peripheral blood of Myasthenia gravis patients.

Myasthenia Gravis (MG) patients with anti-acetylcholine receptor (AChR) antibodies frequently show hyperplastic thymi with ectopic germinal centers, where autoreactive B cells proliferate with the aid of T cells. In this study, thymus and peripheral blood (PB) samples were collected from ten AChR antibody-positive MG patients. T cell receptor (TCR) repertoires were analyzed using next-generation sequencing (NGS), and compared with that of an age and sex matched control group generated from a public database. Certain V genes and VJ gene recombination pairs were significantly upregulated in the TCR chains of αß-T cells in the PB of MG patients compared to the control group. Furthermore, the TCR chains found in the thymi of MG patients had a weighted distribution to longer CDR3 lengths when compared to the PB of MG patients, and the TCR beta chains (TRB) in the MG group's PB showed increased clonality encoded by one upregulated V gene. When TRB sequences were sub-divided into groups based on their CDR3 lengths, certain groups showed decreased clonality in the MG group's PB compared to the control group's PB. Finally, we demonstrated that stereotypic MG patient-specific TCR clonotypes co-exist in both the PB and thymi at a much higher frequency than that of the clonotypes confined to the PB. These results strongly suggest the existence of a biased T cell-mediated immune response in MG patients, as observed in other autoimmune diseases.

Novel targets of ß-TrCP cooperatively accelerate carbohydrate and fatty acid consumption.

Cellular energy is primarily produced from glucose and fat through glycolysis and fatty acid oxidation (FAO) followed by the tricarboxylic acid cycle in mitochondria; energy homeostasis is carefully maintained via numerous feedback pathways. In this report, we uncovered a new master regulator of carbohydrate and lipid metabolism. When ubiquitin E3 ligase ß-TrCP2 was inducibly knocked out in ß-TrCP1 knockout adult mice, the resulting double knockout mice (DKO) lost fat mass rapidly. Biochemical analyses of the tissues and cells from ß-TrCP2 KO and DKO mice revealed that glycolysis, FAO, and lipolysis were dramatically upregulated. The absence of ß-TrCP2 increased the protein stability of metabolic rate-limiting enzymes including 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), adipose triglyceride lipase (ATGL), carnitine palmitoyltransferase 1A (CPT1A), and carnitine/acylcarnitine translocase (CACT). Our data suggest that ß-TrCP is a potential regulator for total energy homeostasis by simultaneously controlling glucose and fatty acid metabolism and that targeting ß-TrCP could be an effective strategy to treat obesity and other metabolic disorders.

Characteristics of microbiome-derived metabolomics according to the progression of alcoholic liver disease.

BACKGROUND AND AIM: The prevalence and severity of alcoholic liver disease (ALD) are increasing. The incidence of alcohol-related cirrhosis has risen up to 2.5%. This study aimed to identify novel metabolite mechanisms involved in the development of ALD in patients. The use of gut microbiome-derived metabolites is increasing in targeted therapies. Identifying metabolic compounds is challenging due to the complex patterns that have long-term effects on ALD. We investigated the specific metabolite signatures in ALD patients. METHODS: This study included 247 patients (heathy control, HC: n = 62, alcoholic fatty liver, AFL; n = 25, alcoholic hepatitis, AH; n = 80, and alcoholic cirrhosis, AC, n = 80) identified, and stool samples were collected. 16S rRNA sequencing and metabolomics were performed with MiSeq sequencer and liquid chromatography coupled to time-of-flight-mass spectrometry (LC-TOF-MS), respectively. The untargeted metabolites in AFL, AH, and AC samples were evaluated by multivariate statistical analysis and metabolic pathotypic expression. Metabolic network classifiers were used to predict the pathway expression of the AFL, AH, and AC stages. RESULTS: The relative abundance of Proteobacteria was increased and the abundance of Bacteroides was decreased in ALD samples (p = 0.001) compared with that in HC samples. Fusobacteria levels were higher in AH samples (p = 0.0001) than in HC samples. Untargeted metabolomics was applied to quantitatively screen 103 metabolites from each stool sample. Indole-3-propionic acid levels are significantly lower in AH and AC (vs. HC, p = 0.001). Indole-3-lactic acid (ILA: p = 0.04) levels were increased in AC samples. AC group showed an increase in indole-3-lactic acid (vs. HC, p = 0.040) level. Compared with that in HC samples, the levels of short-chain fatty acids (SCFAs: acetic acid, butyric acid, propionic acid, iso-butyric acid, and iso-valeric acid) and bile acids (lithocholic acids) were significantly decreased in AC. The pathways of linoleic acid metabolism, indole compounds, histidine metabolism, fatty acid degradation, and glutamate metabolism were closely associated with ALD metabolism. CONCLUSIONS: This study identified that microbial metabolic dysbiosis is associated with ALD-related metabolic dysfunction. The SCFAs, bile acids, and indole compounds were depleted during ALD progression. CLINICAL TRIAL: Clinicaltrials.gov, number NCT04339725.

Completely Resectable (cT1-2) Esophageal Squamous Cell Carcinoma with Minimal Lymph Node Involvement (cN1): Is Neoadjuvant Chemoradiation Therapy the Only Viable Treatment Option?

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) is recommended when lymph node metastasis is evident or strongly suspected on preoperative imaging studies, even for a completely resectable (cT1-2) tumor with minimal lymph node involvement (cN1). We evaluated the validity of upfront surgical approach in this patient group. METHODS: We retrospectively reviewed data from 247 patients with cT1-2 esophageal squamous cell carcinoma (ESCC) who underwent upfront radical esophagectomy followed by the pathology-based adjuvant treatment. Oncologic outcomes of cN1 patients were compared with those of cN0 patients. RESULTS: There were 203 cN0 and 44 cN1 patients. The lymph node yield was 62.0 (interquartile range [IQR], 51.0-76.0) in cN0 and 65.5 (IQR, 57.5-85.0) in cN1 patients (p = 0.033). The size of metastatic node was 0.6 cm (IQR, 0.4-0.9 cm) in cN0 and 0.8 cm (IQR, 0.5-1.3 cm) in cN1 patients (p = 0.001). Nodal upstaging was identified in 29.1% of cN0 and 40.9% of cN1 patients, whereas 18.2% of the cN1 had no actual lymph node metastasis (pN0). The 5-year disease-free survival rate was not significantly different between the groups (cN0, 74.4%; cN1, 71.8%; p = 0.529). Survival rates were closely correlated with pN stage, and a multivariate analysis revealed that pN2-3 stage was a risk factor for poor disease-free survival. CONCLUSIONS: Upfront radical surgery provided accurate nodal staging information, potentially sparing some cN1 patients from unnecessary nCRT while demonstrating comparable survival rates. It might be a valid option for the treatment of cT1-2N1 ESCC.

Transcriptome analysis of skeletal muscle in dermatomyositis, polymyositis, and dysferlinopathy, using a bioinformatics approach.

Background: Polymyositis (PM) and dermatomyositis (DM) are two distinct subgroups of idiopathic inflammatory myopathies. Dysferlinopathy, caused by a dysferlin gene mutation, usually presents in late adolescence with muscle weakness, degenerative muscle changes are often accompanied by inflammatory infiltrates, often resulting in a misdiagnosis as polymyositis. Objective: To identify differential biological pathways and hub genes related to polymyositis, dermatomyositis and dysferlinopathy using bioinformatics analysis for understanding the pathomechanisms and providing guidance for therapy development. Methods: We analyzed intramuscular ribonucleic acid (RNA) sequencing data from seven dermatomyositis, eight polymyositis, eight dysferlinopathy and five control subjects. Differentially expressed genes (DEGs) were identified by using DESeq2. Enrichment analyses were performed to understand the functions and enriched pathways of DEGs. A protein-protein interaction (PPI) network was constructed, and clarified the gene cluster using the molecular complex detection tool (MCODE) analysis to identify hub genes. Results: A total of 1,048, 179 and 3,807 DEGs were detected in DM, PM and dysferlinopathy, respectively. Enrichment analyses revealed that upregulated DEGs were involved in type 1 interferon (IFN1) signaling pathway in DM, antigen processing and presentation of peptide antigen in PM, and cellular response to stimuli in dysferlinopathy. The PPI network and MCODE cluster identified 23 genes related to type 1 interferon signaling pathway in DM, 4 genes (PDIA3, HLA-C, B2M, and TAP1) related to MHC class 1 formation and quality control in PM, and 7 genes (HSPA9, RPTOR, MTOR, LAMTOR1, LAMTOR5, ATP6V0D1, and ATP6V0B) related to cellular response to stress in dysferliniopathy. Conclusion: Overexpression of genes related to the IFN1 signaling pathway and major histocompatibility complex (MHC) class I formation was identified in DM and PM, respectively. In dysferlinopathy, overexpression of HSPA9 and the mTORC1 signaling pathway genes was detected.

Network-based drug repurposing for HPV-associated cervical cancer.

In women, cervical cancer (CC) is the fourth most common cancer around the world with average cases of 604,000 and 342,000 deaths per year. Approximately 50% of high-grade CC are attributed to human papillomavirus (HPV) types 16 and 18. Chances of CC in HPV-positive patients are 6 times more than HPV-negative patients which demands timely and effective treatment. Repurposing of drugs is considered a viable approach to drug discovery which makes use of existing drugs, thus potentially reducing the time and costs associated with de-novo drug discovery. In this study, we present an integrative drug repurposing framework based on a systems biology-enabled network medicine platform. First, we built an HPV-induced CC protein interaction network named HPV2C following the CC signatures defined by the omics dataset, obtained from GEO database. Second, the drug target interaction (DTI) data obtained from DrugBank, and related databases was used to model the DTI network followed by drug target network proximity analysis of HPV-host associated key targets and DTIs in the human protein interactome. This analysis identified 142 potential anti-HPV repurposable drugs to target HPV induced CC pathways. Third, as per the literature survey 51 of the predicted drugs are already used for CC and 33 of the remaining drugs have anti-viral activity. Gene set enrichment analysis of potential drugs in drug-gene signatures and in HPV-induced CC-specific transcriptomic data in human cell lines additionally validated the predictions. Finally, 13 drug combinations were found using a network based on overlapping exposure. To summarize, the study provides effective network-based technique to quickly identify suitable repurposable drugs and drug combinations that target HPV-associated CC.

Ocean fronts as decadal thermostats modulating continental warming hiatus.

Over the past decade, an unexpected cooling trend has been observed in East Asia and North America during winter. Climate model simulations suggest that this pattern of stalled warming, besides accelerated warming, will repeat throughout the course of global warming, influenced by the natural decade-long variations in the climate system. However, understanding the exact factors affecting the pace of warming remains a challenge. Here we show that a pause in warming over continental areas-namely, local warming hiatus-can be accompanied by excessive heat accumulation north of the ocean fronts. This oceanic condition, often manifesting in the form of marine heatwaves, constrains the subseasonal growth of atmospheric planetary waves, significantly increasing the likelihood of cold extremes in downstream continents. Our results underscore the importance of closely monitoring changing ocean fronts in response to human-induced warming, which can potentially reshape the inherent decade-long fluctuations within regional climates over the long term.

Two weeks dose range-finding and four weeks repeated dose oral toxicity study of a novel reversible monoamine oxidase B inhibitor KDS2010 in cynomolgus monkeys.

A novel reversible monoamine oxidase B inhibitor, KDS2010, has been developed as a therapeutic candidate for neurodegenerative diseases. This study investigated its potential toxicity in non-human primates before human clinical trials. Daily KDS2010 doses (25, 50, or 100 mg/kg) were orally administered to cynomolgus monkeys (1 animal/sex/group, 4 males and 4 females) for 2 weeks to determine the dose range. One male was moribund, and one female was found dead in the 100 mg/kg/day group. One male was also found dead in the 50 mg/kg/day group. The death was considered an adverse effect in both sexes since distal tubules/collecting duct dilation and hypertrophy in the epithelium of the papillary duct were observed in their kidneys. Based on dose range finding results, KDS2010 (10, 20, or 40 mg/kg/day) was administered orally for 4 weeks, and animals were given 2 weeks for recovery. No significant changes were observed during daily clinical observations and macro-and microscopic examinations, including body weight, food consumption, hematology, clinical chemistry, and organ weight. And, the kidney was seen as the primary target organ of KDS2010 in the 2 weeks study, but no adverse effect was observed in the 4 weeks study. Therefore, 40 mg/kg/day is considered the no-observed-adverse-effect level in both sexes of cynomolgus monkeys. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00182-4.

IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene, ofd1.

BACKGROUND: The cilia are microtubule-based organelles that protrude from the cell surface. Abnormalities in cilia result in various ciliopathies, including polycystic kidney disease (PKD), Bardet-Biedl syndrome (BBS), and oral-facial-digital syndrome type I (OFD1), which show genetic defects associated with cilia formation. Although an increasing number of human diseases is attributed to ciliary defects, the functions or regulatory mechanisms of several ciliopathy genes remain unclear. Because multi ciliated cells (MCCs) are especially deep in vivo, studying ciliogenesis is challenging. Here, we demonstrate that ik is essential for ciliogenesis in vivo. RESULTS: In the absence of ik, zebrafish embryos showed various ciliopathy phenotypes, such as body curvature, abnormal otoliths, and cyst formation in the kidney. RNA sequencing analysis revealed that ik positively regulated ofd1 expression required for cilium assembly. In fact, depletion of ik resulted in the downregulation of ofd1 expression with ciliary defects, and these ciliary defects in ik mutants were rescued by restoring ofd1 expression. Interestingly, ik affected ciliogenesis particularly in the proximal tubule but not in the distal tubule in the kidney. CONCLUSIONS: This study demonstrates the role of ik in ciliogenesis in vivo for the first time. Loss of ik in zebrafish embryos displays various ciliopathy phenotypes with abnormal ciliary morphology in ciliary tissues. Our findings on the ik-ofd1 axis provide new insights into the biological function of ik in clinical ciliopathy studies in humans.

Validation of a deep learning-based software for automated analysis of T2 mapping in cardiac magnetic resonance imaging.

Background: The reliability and diagnostic performance of deep learning (DL)-based automated T2 measurements on T2 map of 3.0-T cardiac magnetic resonance imaging (MRI) using multi-institutional datasets have not been investigated. We aimed to evaluate the performance of a DL-based software for measuring automated T2 values from 3.0-T cardiac MRI obtained at two centers. Methods: Eighty-three subjects were retrospectively enrolled from two centers (42 healthy subjects and 41 patients with myocarditis) to validate a commercial DL-based software that was trained to segment the left ventricular myocardium and measure T2 values on T2 mapping sequences. Manual reference T2 values by two experienced radiologists and those calculated by the DL-based software were obtained. The segmentation performance of the DL-based software and the non-inferiority of automated T2 values were assessed compared with the manual reference standard per segment level. The software's performance in detecting elevated T2 values was assessed by calculating the sensitivity, specificity, and accuracy per segment. Results: The average Dice similarity coefficient for segmentation of myocardium on T2 maps was 0.844. The automated T2 values were non-inferior to the manual reference T2 values on a per-segment analysis (45.35 vs. 44.32 ms). The DL-based software exhibited good performance (sensitivity: 83.6-92.8%; specificity: 82.5-92.0%; accuracy: 82.7-92.2%) in detecting elevated T2 values. Conclusions: The DL-based software for automated T2 map analysis yields non-inferior measurements at the per-segment level and good performance for detecting myocardial segments with elevated T2 values compared with manual analysis.

Significant wave height prediction from X-band marine radar images using deep learning with 3D convolutions.

This research introduces a deep learning method for ocean wave height estimation utilizing a Convolutional Neural Network (CNN) based on the VGGNet. The model is trained on a dataset comprising buoy wave heights and radar images, both critical for marine engineering. The dataset features X-band radar images sourced from Sokcho, Republic of Korea, spanning from June 1, 2021, to August 13, 2021. This collection amounts to 72,180 three-dimensional images, gathered at intervals of approximately 1.43 seconds. The data collected was highly unbalanced in terms of wave heights, with images of lower wave heights being more common. To deal with data imbalances in the wave height datasets, we categorized the data into three groups based on wave heights and applied stratified random sampling at each level. This approach balances the data patches for each training iteration, reducing the risk of overfitting and promoting learning from diverse data. We also implemented a system to protect data in groups with fewer instances, ensuring fair representation across all categories. This study presents a deep learning regression model for predicting wave height values from radar images. The model extracts features from sequences of 64 radar images using three-dimensional convolutions for both temporal and spatial learning. Using three-dimensional convolutions, the model captures temporal features in radar image sequences and provides accurate wave height estimates with an RMSE of 0.3576 m. The study derived results using radar images under different wave height conditions for 74 days to ensure reliability.

Current status of image-enhanced endoscopy in inflammatory bowel disease.

In inflammatory bowel disease (IBD), chronic inflammation leads to unfavorable clinical outcomes and increases the risk of developing colorectal neoplasm (CRN); thereby highlighting the importance of endoscopically evaluating disease activity as well as detecting and characterizing CRN in patients with IBD. With recent advances in image-enhanced endoscopic (IEE) technologies, especially virtual chromoendoscopy (VCE) platforms, this review discusses state-of-the-art IEE techniques and their applicability in assessing disease activity and surveillance colonoscopy in patients with IBD. Among various IEE, VCE demonstrated the capacity to identify quiescent disease activity. And endoscopic remission defined by the new scoring system using VCE platform better predicted clinical outcomes, which may benefit the tailoring of therapeutic strategies in patients with IBD. High-definition dye-chromoendoscopy (HD-DCE) is numerically superior to high-definition white light endoscopy (HD-WLE) in detecting CRN in IBD; however, discrepancy is observed in the statistical significance. VCE showed comparable performance in detecting dysplasia to HD-WLE or DCE and potential for optical diagnosis to differentiate neoplastic from nonneoplastic lesions during surveillance colonoscopy. Applying these novel advanced IEE technologies would provide opportunities for personalized medicine in IBD and optimal treatment of CRN in patients with IBD.

Analysis of the prescription trends of potentially inappropriate medications in Korean older outpatients by sex: A retrospective study using data from the health insurance review and assessment service.

This study aimed to determine the policy implications for drug management by identifying the prescription trends of potentially inappropriate medications (PIMs) in older outpatients. Considering the Drug Utilization Review and Korean version of the standards for PIMs based on the Beers Criteria, 141 ingredients were selected that spanned over 7 years of health insurance claims data analysis. During the study period, the number of patients and claims related to PIMs increased. Although the number of health insurance claims decreased in 2020 owing to coronavirus disease (COVID-19), it increased again in 2021. Tamsulosin was the most frequently prescribed drug for male patients, followed by alprazolam and zolpidem. For female patients, eperisone was the most frequently prescribed drug, followed by alprazolam, zolpidem, and etizolam. In Korea, health insurance claims for PIMs decreased in 2020 owing to the COVID-19 pandemic. However, an overall increasing trend was observed from 2015 to 2021. Moreover, during this period, the prescription trend of benzodiazepine-type drugs and zolpidem increased in both male and female patients. Therefore, management policies regarding PIMs and drug ingredients, such as benzodiazepines and zolpidem, are required.