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Abstract Spinal myxopapillary ependymoma (MPE) and schwannoma represent clinically distinct intradural extramedullary tumors, albeit with shared and overlapping magnetic resonance imaging (MRI) characteristics. We aimed to identify significant MRI features that can differentiate between MPE and schwannoma and develop a novel prediction model using these features. In this study, 77 patients with MPE (n = 24) or schwannoma (n = 53) who underwent preoperative MRI and surgical removal between January 2012 and December 2022 were included. MRI features, including intratumoral T2 dark signals, subarachnoid hemorrhage (SAH), leptomeningeal seeding, and enhancement patterns, were analyzed. Logistic regression analysis was conducted to distinguish between MPE and schwannomas based on MRI parameters, and a prediction model was developed using significant MRI parameters. The model was validated internally using a stratified tenfold cross-validation. The area under the curve (AUC) was calculated based on the receiver operating characteristic curve analysis. MPEs had a significantly larger mean size (p = 0.0035), higher frequency of intratumoral T2 dark signals (p = 0.0021), associated SAH (p = 0.0377), and leptomeningeal seeding (p = 0.0377). Focal and diffuse heterogeneous enhancement patterns were significantly more common in MPEs (p = 0.0049 and 0.0038, respectively). Multivariable analyses showed that intratumoral T2 dark signal (p = 0.0439) and focal (p = 0.0029) and diffuse enhancement patterns (p = 0.0398) were independent factors. The prediction model showed an AUC of 0.9204 (95% CI 0.8532–0.9876) and the average AUC for internal validation was 0.9210 (95% CI 0.9160–0.9270). MRI provides useful data for differentiating spinal MPEs from schwannomas. The prediction model developed based on the MRI features demonstrated excellent discriminatory performance.

Abstract Background We investigated the prognostic significance of body mass index in small‐cell lung cancer and explored whether skeletal muscle status affects the body mass index–survival relationship. Methods This retrospective study evaluated data from patients who underwent platinum‐etoposide chemotherapy for small‐cell lung cancer between March 2010 and December 2021. Skeletal muscle status was assessed using non‐contrast computed tomography images of baseline positron‐emission tomography‐computed tomography, with the skeletal muscle index defined as the cross‐sectional area of skeletal muscle divided by height squared, and the average attenuation values of skeletal muscle. Cox proportional hazards regression analysis was used to determine the correlations of body mass index, skeletal muscle metrics, and overall survival. Results We analysed the data of 1146 Asian patients (1006 men and 140 women, with a median age of 67 years [interquartile range: 61–72 years]), including 507 and 639 patients with limited and extensive disease, respectively. Being underweight, defined as a body mass index

Mutations in the SACS gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of Charcot-Marie-Tooth disease (CMT). This study aimed to identify SACS mutations in a Korean CMT cohort with cerebellar ataxia and spasticity by whole exome sequencing (WES). As a result, eight pathogenic SACS mutations in four families were identified as the underlying causes of these complex phenotypes. The prevalence of CMT families with SACS mutations was determined to be 0.3%. All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was performed in four patients and all had fatty replacements. Of note, they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without SACS mutations who had distal dominant fatty involvement. Therefore, these findings were considered a characteristic feature in CMT patients with SACS mutations. Although further studies with more cases are needed, our results highlight lower extremity MRI findings in CMT patients with SACS mutations and broaden the clinical spectrum. We suggest screening for SACS in recessive CMT patients with complex phenotypes of ataxia and spasticity.

Purpose Infants in the neonatal intensive care unit (NICU) often show cardiorespiratory deterioration during gavage feeding. We aimed to determine whether slow infusion intermittent feeding (SIIF) can reduce respiratory deterioration during gavage feeding in preterm infants in the NICU. Methods Data on preterm infants whose gavage feeding method was changed to SIIF (1-­­hour infusion with an infusion pump and 2-­hour rest within a 3­-hour interval) from bolus gravity feeding (2-­ or 3-­hour interval) due to feeding­-associated cardiorespiratory deterioration were retrospectively reviewed. A significant cardiorespiratory event was defined as a saturation level below 80% or heart rate below 80 bpm. We compared the frequency of cardiorespiratory events and the level of respiratory support 24 hours before and after the application of SIIF. Results A total of 34 infants were enrolled and analyzed. The total frequency of desaturation or bradycardia significantly decreased after SIIF application (8.94 vs. 5.03, P=0.001). The frequency of feeding-­related bradycardia and desaturation also significantly decreased (4.15 vs. 1.68, P=0.008). Out of 34 patients, 11 (32.4%) had a decreased level of ventilator support within 1 day after SIIF. The respiratory severity scores of the 10 patients who received invasive ventilator support decreased significantly after SIIF (5.24 vs. 4.59, P=0.032). Conclusion SIIF significantly decreased gavage feeding­-associated cardiorespiratory events and reduced respiratory support in approximately one-­third of subjects. Therefore, SIIF may be a therapeutic option for gavage feed-­associated respiratory deterioration in preterm infants in the NICU.

We aimed to develop efficient data labeling strategies for ground truth segmentation in lower-leg magnetic resonance imaging (MRI) of patients with Charcot-Marie-Tooth disease (CMT) and to develop an automated muscle segmentation model using different labeling approaches. The impact of using unlabeled data on model performance was further examined. Using axial T1-weighted MRIs of 120 patients with CMT (60 each with mild and severe intramuscular fat infiltration), we compared the performance of segmentation models obtained using several different labeling strategies. The effect of leveraging unlabeled data on segmentation performance was evaluated by comparing the performances of few-supervised, semi-supervised (mean teacher model), and fully-supervised learning models. We employed a 2D U-Net architecture and assessed its performance by comparing the average Dice coefficients (ADC) using paired t-tests with Bonferroni correction. Among few-supervised models utilizing 10% labeled data, labeling three slices (the uppermost, central, and lowermost slices) per subject exhibited a significantly higher ADC (90.84±3.46%) compared with other strategies using a single image slice per subject (uppermost, 87.79±4.41%; central, 89.42±4.07%; lowermost, 89.29±4.71%, p < 0.0001) or all slices per subject (85.97±9.82%, p < 0.0001). Moreover, semi-supervised learning significantly enhanced the segmentation performance. The semi-supervised model using the three-slices strategy showed the highest segmentation performance (91.03±3.67%) among 10% labeled set models. Fully-supervised model showed an ADC of 91.39±3.76. A three-slice-based labeling strategy for ground truth segmentation is the most efficient method for developing automated muscle segmentation models of CMT lower leg MRI. Additionally, semi-supervised learning with unlabeled data significantly enhances segmentation performance.

BackgroundAutonomic neuropathy commonly occurs as a long-term complication of diabetes mellitus (DM) and can be diagnosed based on heart rate variability (HRV), calculated from electrocardiogram (ECG) recordings. There are limited data on HRV using real-time ECG and ambulatory glucose monitoring in patients with DM. The aim of this study was to investigate real-time HRV according to ambulatory glucose levels in patients with DM.MethodsA total of 43 patients (66.3 ± 7.5 years) with DM underwent continuous real-time ECG monitoring (225.7 ± 107.3 h) for HRV and ambulatory glucose monitoring using a remote monitoring system. We compared the HRV according to the ambulatory glucose profile. Data were analyzed according to the target in glucose range (TIR).ResultsThere were no significant differences in the baseline characteristics of the patients according to the TIR. During monitoring, we checked ECG and ambulatory glucose levels (a total of 15,090 times) simultaneously for all patients. Both time- and frequency-domain HRVs were lower when the patients had poorly controlled glucose levels (TIR 70%). In addition, heart and respiratory rates increased with real-time glucose levels (P

Background: Autonomic dysfunction as a long-term complication may occur in end-stage kidney disease (ESKD) patients and can be diagnosed using heart rate variability (HRV) analyzed from electrocardiogram (ECG) recordings. There is limited data about HRV using real-time ECG to predict hemodialysis (HD) efficiency in patients with ESKD who are routinely doing HD in the real world. Methods: A total of 50 patients (62.1 ± 10.7 years) with ESKD underwent continuous real-time ECG monitoring (237.4 ± 15.3 min) during HD for HRV using remote monitoring system. Their electrolyte levels were checked before and after HD. We compared HRV according to electrolyte levels. Results: During the monitor, we checked the ECG and electrolyte levels simultaneously a total of 2374 times for all of the patients. Both time and frequency domain HRV were higher when the patients had lower K+ level (+ level change (+ level (≥0.5 mEq/L) and P+ level change (≥2 mEq/L). Additionally, patients with lower K+ and P+ level change groups had higher incidences of arrhythmic events including atrial/ventricular premature complexes, despite no difference of mean heart rate (p < 0.001). Conclusions: Higher HRV was independently associated with a poorly controlled K+ and P+ level during HD in patients with ESKD. This is consistently evidenced by the independent association between higher HRV, K+ and P+ levels in real time, suggesting that low electrolyte changes before and after HD alone may cause cardiac autonomic dysfunction.

Abstract We aimed to derive comprehensive MRI parameters that reflect intramuscular fat infiltration severity for designated lower extremity levels, based on semiquantitative analyses in Charcot-Marie-Tooth disease type 1A (CMT1A) patients. We reviewed lower extremity MRIs of 116 CMT1A patients. Intramuscular fat infiltration grading using the Mercuri scale was performed for the non-dominant lower extremity at three levels (proximal, mid, and distal) for the thigh and at two levels (proximal and distal) for the lower leg. Based on MRI results, the following parameters were calculated for each level and for entire muscles: fat infiltration proportion (FIP), significant fat infiltration proportion (SigFIP), and severe fat infiltration proportion (SevFIP). The relationships between the MRI parameters and clinical data were evaluated using Spearman’s correlation analysis. FIP, SigFIP, and SevFIP measured for entire muscles significantly correlated with Charcot-Marie-Tooth Neuropathy Score (p

Abstract Background Although the obesity paradox is a topic of immense interest for oncologists and epidemiologists, the mechanism underlying this unexpected benefit of obesity is poorly understood. We explored the prognostic value of obesity and its association with skeletal muscle mass. Methods This retrospective study evaluated the data of patients who underwent surgical excision for lung adenocarcinoma between January 2011 and December 2015. Body mass index was categorized according to the criteria of the Asia‐Pacific classification. Cross‐sectional areas of the skeletal muscle, subcutaneous fat, and visceral fat were measured. Skeletal muscle mass status was defined based on the cut‐offs of skeletal muscle index (cm2/m2), calculated as the area of skeletal muscle divided by height squared. Overall survival was estimated using the Kaplan–Meier method, and differences in survival probabilities were compared using the log‐rank test. Cox proportional hazards regression analysis was conducted to determine the association with overall survival. Results A total of 636 patients with a median age of 61 years (interquartile range, 54.0–68.5 years; 321 men and 315 women) were included. Obese patients (body mass index ≥ 25 kg/m2) had longer overall survival than non‐obese patients (mean, 110.2 months vs. 98.7 months; log‐rank P = 0.015). Under multivariable Cox proportional hazard regression analysis, obesity was associated with longer overall survival after adjusting for covariates (hazard ratio, 0.59; 95% confidence interval, 0.40–0.86; P = 0.007). The prognostic value of obesity remained and predicted favourable overall survival after additional adjusting for skeletal muscle mass status (hazard ratio, 0.57; 95% confidence interval, 0.36–0.89; P = 0.014), skeletal muscle index (hazard ratio, 0.53; 95% confidence interval, 0.33–0.84; P = 0.008), or skeletal muscle area (hazard ratio, 0.61; 95% confidence interval, 0.38–0.98; P = 0.041). No association was observed between skeletal muscle mass status and the impact of body mass index on overall survival (P for interaction = 0.512). Conclusions Obesity was associated with favourable overall survival, independent of skeletal muscle mass, after surgical excision of lung adenocarcinoma.

Abstract This study aimed to investigate whether in vivo MR-electrical properties tomography (MR-EPT) is feasible in musculoskeletal tissues by evaluating the conductivity of muscle, cartilage, and peripheral nerve around the knee joint, and to explore whether these measurements change after exercise. This prospective study was approved by the institutional review board. On February 2020, ten healthy volunteers provided written informed consent and underwent MRI of the right knee using a three-dimensional balanced steady-state free precession (bSSFP) sequence. To test the effect of loading, the subjects performed 60 squatting exercises after baseline MRI, immediately followed by post-exercise MRI with the same sequences. After reconstruction of conductivity map based on the bSSFP sequence, conductivity of muscles, cartilages, and nerves were measured. Measurements between the baseline and post-exercise MRI were compared using the paired t-test. Test–retest reliability for baseline conductivity was evaluated using the intraclass correlation coefficient. The baseline and post-exercise conductivity values (mean ± standard deviation) [S/m] of muscles, cartilages, and nerves were 1.73 ± 0.40 and 1.82 ± 0.50 (p = 0.048), 2.29 ± 0.47 and 2.51 ± 0.37 (p = 0.006), and 2.35 ± 0.57 and 2.36 ± 0.57 (p = 0.927), respectively. Intraclass correlation coefficient for the baseline conductivity of muscles, cartilages, and nerves were 0.89, 0.67, and 0.89, respectively. In conclusion, in vivo conductivity measurement of musculoskeletal tissues is feasible using MR-EPT. Conductivity of muscles and cartilages significantly changed with an overall increase after exercise.

Abstract The objectives of this study were to assess the fat fraction (FF) and cross-sectional area (CSA) of the sciatic nerve in Charcot-Marie-Tooth disease type 1A (CMT1A) patients using Dixon-based proton density fat quantification MRI and to elucidate its potential association with clinical parameters. Thigh MRIs of 18 CMT1A patients and 18 age- and sex-matched volunteers enrolled for a previous study were reviewed. Analyses for FF and CSA of the sciatic nerve were performed at three levels (proximal to distal). CSA and FF were compared between the two groups and among the different levels within each group. The relationship between the MRI parameters and clinical data were assessed in the CMT1A patients. The CMT1A patients showed significantly higher FF at level 3 (p = 0.0217) and significantly larger CSA at all three levels compared with the control participants (p

This study aimed to elucidate the structural congeners of natural izenamides A, B, and C (1–3) responsible for cathepsin D (CTSD) inhibition. Structurally modified izenamides were synthesized and biologically evaluated, and their biologically important core structures were identified. We confirmed that the natural statine (Sta) unit (3S,4S)-γ-amino-β-hydroxy acid is a requisite core structure of izenamides for inhibition of CTSD, which is closely related to the pathophysiological roles in numerous human diseases. Interestingly, the statine-incorporated izenamide C variant (7) and 18-epi-izenamide B variant (8) exhibited more potent CTSD-inhibitory activities than natural izenamides.

Abstract Charcot–Marie–Tooth disease (CMT) is the most common hereditary peripheral neuropathy. Mutations in the neurofilament light polypeptide (NEFL) gene produce diverse clinical phenotypes, including demyelinating (CMT1F), axonal (CMT2E), and intermediate (CMTDIG) neuropathies. From 2005 to 2020, 1,143 Korean CMT families underwent gene sequencing, and we investigated the clinical, genetic, and neuroimaging spectra of NEFL‐related CMT patients. Ten NEFL mutations in 17 families (1.49%) were identified, of which three (p.L312P, p.Y443N, and p.K467N) were novel. Eight de novo cases were identified at a rate of 0.47 based on a cosegregation analysis. The age of onset was ≤3 years in five cases (13.5%). The patients revealed additional features including delayed walking, ataxia, dysphagia, dysarthria, dementia, ptosis, waddling gait, tremor, hearing loss, and abnormal visual evoked potential. Signs of ataxia were found in 26 patients (70.3%). In leg MRI analyses, various degrees of intramuscular fat infiltration were found. All compartments were evenly affected in CMT1F patients. The anterior and anterolateral compartments were affected in CMT2E, and the posterior compartment was affected in CMTDIG. Thus, NEFL‐related CMT patients showed phenotypic heterogeneities. This study's clinical, genetic, and neuroimaging results could be helpful in the evaluation of novel NEFL variants and differential diagnosis against other CMT subtypes.

Fibrosis has various biological processes and affects almost every organ, especially in patients with inflammatory bowel disease, including Crohn’s disease, who experience discomfort caused by intestinal fibrosis, which is a problem that needs to be resolved. TGF-β signaling is known to act as a key regulator of intestinal fibrosis, and its modulation could be an excellent candidate for fibrosis therapy. Xanthohumol (XN) has various effects, including anti-inflammation and anti-cancer; however, the detailed mechanism of TGF-β signaling has not yet been studied. The purpose of this study was to investigate the mechanism underlying the anti-fibrotic effect of XN on TGF-β1-induced intestinal fibrosis using primary human intestinal fibroblasts (HIFs). In this study, to check the anti-fibrotic effects of XN on intestinal fibrosis, we assessed the expression of fibrosis-related genes in TGF-β1-stimulated HIFs by qPCR, immunoblotting, and immunofluorescence staining. As a result, XN showed the ability to reduce the expression of fibrosis-associated genes increased by TGF-β1 treatment in HIFs and restored the cell shape altered by TGF-β1. In particular, XN repressed both NF-κB- and Smad-binding regions in the α-SMA promoter, which is important in fibrosis. In addition, XN inhibited NF-κB signaling, including phosphorylated-IkBα and cyclooxygenase-2 expression, and TNF-α-stimulated transcriptional activity of NF-κB. XN attenuated TGF-β1-induced phosphorylation of Smad2 and Smad3, and the transcriptional activity of CAGA. Particularly, XN interfered with the binding of TGF-Receptor I (TβRI) and Smad3 by binding to the kinase domain of the L45 loop of TβRI, thereby confirming that the fibrosis mechanism did not proceed further. In conclusion, XN has an inhibitory effect on TGF-β1-induced intestinal fibrosis in HIFs, significantly affecting TGF-β/Smad signaling.

This paper reports a concise and scalable method for the synthesis of the phytoestrogen 7,2′-dihydroxy-4′,5′-dimethoxyisoflavanone 1 via an optimized synthetic route. Compound 1 was readily obtained in 11 steps and 11% overall yield on a gram scale from commercially available 3,4-dimethoxyphenol. The key features of the synthesis include the construction of the deoxybenzoin unit through a sequence of Claisen rearrangement, oxidative cleavage, and aryllithium addition and the efficient synthesis of the isoflavanone architecture from highly functionalized 2-hydroxyketone.

Although radiation therapy (RT) plays an important role in the palliation of localized bone metastases, there is no consensus on a reliable method for evaluating treatment response. Therefore, we retrospectively evaluated the potential of magnetic resonance imaging (MRI) using apparent diffusion coefficient (ADC) maps and conventional images in whole-tumor volumetric analysis of texture features for assessing treatment response after RT. For this purpose, 28 patients who received RT for osteolytic bone metastasis and underwent both pre- and post-RT MRI were enrolled. Volumetric ADC histograms and conventional parameters were compared. Cox regression analyses were used to determine whether the change ratio in these parameters was associated with local disease progression-free survival (LDPFS). The ADCmaximum, ADCmean, ADCmedian, ADCSD, maximum diameter, and volume of the target lesions after RT significantly increased. Change ratios of ADCmean < 1.41, tumor diameter ≥ 1.17, and tumor volume ≥ 1.55 were significant predictors of poor LDPFS. Whole-tumor volumetric ADC analysis might be utilized for monitoring patient response to RT and potentially useful in predicting clinical outcomes.

Ionic liquids (ILs) have attracted significant interest because of their desirable properties. These characteristics have improved their application to overcome the shortcomings of conventional separation techniques for phytochemicals. In this study, several ILs were investigated for their capacity to extract isoimperatorin, a bioactive furanocoumarin, from the roots of Ostericum koreanum. Herein, 1-Butyl-3-methylimidazolium tetrafluoroborate ([Bmim][BF4]) was selected as a promising IL for separating isoimperatorin. A central composite design was applied to optimize the extraction conditions. Under the optimal conditions, the yield of isoimperatorin reached 97.17 ± 1.84%. Additionally, the recovery of isoimperatorin from the [Bmim][BF4] solution was successfully achieved (87.73 ± 2.37%) by crystallization using water as an antisolvent. The purity of the isoimperatorin was greatly enhanced, from 0.26 ± 0.28% in the raw material to 26.94 ± 1.26% in the product, in a one-step crystallization process. Namely, an enhancement of approximately 103-folds was reached. The developed approach overcomes the shortcomings of conventional separation methods applied for gaining isoimperatorin by significantly reducing the laboriousness of the process and the consumption of volatile organic solvents. Moreover, the simplicity and effectiveness of the method are assumed to be valuable for producing isoimperatorin-enriched products and for promoting its purification. This work also confirms the efficiency of ILs as a promising material for the separation of phytochemicals.