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Abstract Gangliosides in the brain play a crucial role in modulating the integrity of vertebrate central nervous system in a region-specific manner. However, to date, a comprehensive structural elucidation of complex intact ganglioside isomers has not been achieved, resulting in the elusiveness into related molecular mechanism. Here, we present a glycolipidomic approach for isomer-specific and brain region-specific profiling of the mouse brain. Considerable region-specificity and commonality in specific group of regions are highlighted. Notably, we observe a similarity in the abundance of major isomers, GD1a and GD1b, within certain regions, which provides significant biological implications with interpretation through the lens of a theoretical retrosynthetic state-transition network. Furthermore, A glycocentric-omics approaches using gangliosides and N-glycans reveal a remarkable convergence in spatial dynamics, providing valuable insight into molecular interaction network. Collectively, this study uncovers the spatial dynamics of intact glyco-conjugates in the brain, which are relevant to regional function and accelerates the discovery of potential therapeutic targets for brain diseases.

Abstract Background Physiologic MRI-based tumor habitat analysis has the potential to predict patient outcomes by identifying the spatiotemporal habitats of glioblastoma. This study aims to prospectively validate the cut-off for tumor progression obtained from tumor habitat analysis based on physiologic MRI in ascertaining time-to-progression (TTP) and the site of progression in glioblastoma patients following concurrent chemoradiotherapy (CCRT). Methods In this prospective study (ClinicalTrials.gov ID: NCT02613988), we will recruit patients with IDH-wild type glioblastoma who underwent CCRT and obtained immediate post-operative and three serial post-CCRT MRI scans within a three-month interval, conducted using diffusion-weighted imaging and dynamic susceptibility contrast imaging. Voxels from cerebral blood volume and apparent diffusion coefficient maps will be grouped using k-means clustering into three spatial habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue). The spatiotemporal habitats of the tumor will be evaluated by comparing changes in each habitat between the serial MRI scans (post-operative and post-CCRT #1, #2, and #3). Associations between spatiotemporal habitats and TTP will be analyzed using cox proportional hazard modeling. The site of progression will be matched with spatiotemporal habitats. Discussion The perfusion- and diffusion-derived tumor habitat in glioblastoma is expected to stratify TTP and may serve as an early predictor for tumor progression in patients with IDH wild-type glioblastoma. Trial registration ClinicalTrials.gov ID: NCT02613988.

Rhabdomyosarcoma (RMS) comprises of heterogeneous group of neoplasms that occasionally express epithelial markers on immunohistochemistry (IHC). We herein report the case of a patient who developed RMS of the skull with EWSR1 fusion and anaplastic lymphoma kinase (ALK) and cytokeratin expression as cytomorphologic features. A 40-year-old man presented with a mass in his forehead. Surgical resection was performed, during which intraoperative frozen specimens were obtained. Squash cytology showed scattered or clustered spindle and epithelioid cells. IHC revealed that the resected tumor cells were positive for desmin, MyoD1, cytokeratin AE1/AE3, and ALK. Although EWSR1 rearrangement was identified on fluorescence in situ hybridization, ALK, and TFCP2 rearrangement were not noted. Despite providing adjuvant chemoradiation therapy, the patient died of tumor progression 10 months after diagnosis. We emphasize that a subset of RMS can express cytokeratin and show characteristic histomorphology, implying the need for specific molecular examination.

Abstract Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management.

Abstract Background The identification of viable tumors and radiation necrosis after stereotactic radiosurgery (SRS) is crucial for patient management. Tumor habitat analysis involving the grouping of similar voxels can identify subregions that share common biology and enable the depiction of areas of tumor recurrence and treatment-induced change. This study aims to validate an imaging biomarker for tumor recurrence after SRS for brain metastasis by conducting tumor habitat analysis using multi-parametric MRI. Methods In this prospective study (NCT05868928), patients with brain metastases will undergo multi-parametric MRI before SRS, and then follow-up MRIs will be conducted every 3 months until 24 months after SRS. The multi-parametric MRI protocol will include T2-weighted and contrast-enhanced T1-weighted imaging, diffusion-weighted imaging, and dynamic susceptibility contrast imaging. Using k-means voxel-wise clustering, this study will define three structural MRI habitats (enhancing, solid low-enhancing, and nonviable) on T1- and T2-weighted images and three physiologic MRI habitats (hypervascular cellular, hypovascular cellular, and nonviable) on apparent diffusion coefficient maps and cerebral blood volume maps. Using RANO-BM criteria as the reference standard, via Cox proportional hazards analysis, the study will prospectively evaluate associations between parameters of the tumor habitats and the time to recurrence. The DICE similarity coefficients between the recurrence site and tumor habitats will be calculated. Discussion The tumor habitat analysis will provide an objective and reliable measure for assessing tumor recurrence from brain metastasis following SRS. By identifying subregions for local recurrence, our study could guide the next therapeutic targets for patients after SRS. Trial registration This study is registered at ClinicalTrials.gov (NCT05868928).

BackgroundPulmonary tuberculosis (PTB) poses a global health challenge owing to the time-intensive nature of traditional diagnostic tests such as smear and culture tests, which can require hours to weeks to yield results. ObjectiveThis study aimed to use artificial intelligence (AI)–based chest radiography (CXR) to evaluate the infectivity of patients with PTB more quickly and accurately compared with traditional methods such as smear and culture tests. MethodsWe used DenseNet121 and visualization techniques such as gradient-weighted class activation mapping and local interpretable model-agnostic explanations to demonstrate the decision-making process of the model. We analyzed 36,142 CXR images of 4492 patients with PTB obtained from Severance Hospital, focusing specifically on the lung region through segmentation and cropping with TransUNet. We used data from 2004 to 2020 to train the model, data from 2021 for testing, and data from 2022 to 2023 for internal validation. In addition, we used 1978 CXR images of 299 patients with PTB obtained from Yongin Severance Hospital for external validation. ResultsIn the internal validation, the model achieved an accuracy of 73.27%, an area under the receiver operating characteristic curve of 0.79, and an area under the precision-recall curve of 0.77. In the external validation, it exhibited an accuracy of 70.29%, an area under the receiver operating characteristic curve of 0.77, and an area under the precision-recall curve of 0.8. In addition, gradient-weighted class activation mapping and local interpretable model-agnostic explanations provided insights into the decision-making process of the AI model. ConclusionsThis proposed AI tool offers a rapid and accurate alternative for evaluating PTB infectivity through CXR, with significant implications for enhancing screening efficiency by evaluating infectivity before sputum test results in clinical settings, compared with traditional smear and culture tests.

Common buckwheat (Fagopyrum esculentum Moench.) is one of the most important orphan crops worldwide. Various research efforts have been done to improve cultivation methods to enhance important agronomic traits such as productivity and biotic/abiotic resistance. One important aspect is the seed trait, which has not been extensively studied due to the time-consuming and tedious nature of its examination. Despite this, understanding seed traits is crucial for meeting consumer needs and optimizing crop yields. Therefore, the aim of the study is to investigate the inheritance of common buckwheat seed traits—such as shape, size, and coat color—using an image-based approach. This method allows for the analysis of a large number of seeds with a level of accuracy and precision that was previously unattainable. The results indicate that seed coat color is inherited maternally. Notably, the parameters in size had substantial increases acting like overdominance. The number of seeds that were harvested from F1s of each cross differed a lot depending on the cross combinations and pin/thrum type. In addition, seed size had large reduction in F1s from the different seed-sized parents, especially in thrum type. These may show that there could be cross barriers. The results revealed trends of maternal inheritance for seed shape and coat color in buckwheat, an area that has not been extensively studied. These findings could support buckwheat breeding efforts, helping to address market needs and food demands in the face of significant climate change.

Abstract Background COPD is associated with the development of lung cancer. A protective effect of inhaled corticosteroids (ICS) on lung cancer is still controversial. Hence, this study investigated the development of lung cancer according to inhaler prescription and comorbidties in COPD. Methods A retrospective cohort study was conducted based on the Korean Health Insurance Review and Assessment Service database. The development of lung cancer was investigated from the index date to December 31, 2020. This cohort included COPD patients (≥ 40 years) with new prescription of inhalers. Patients with a previous history of any cancer during screening period or a switch of inhaler after the index date were excluded. Results Of the 63,442 eligible patients, 39,588 patients (62.4%) were in the long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) group, 22,718 (35.8%) in the ICS/LABA group, and 1,136 (1.8%) in the LABA group. Multivariate analysis showed no significant difference in the development of lung cancer according to inhaler prescription. Multivariate analysis, adjusted for age, sex, and significant factors in the univariate analysis, demonstrated that diffuse interstitial lung disease (DILD) (HR = 2.68; 95%CI = 1.86–3.85), a higher Charlson Comorbidity Index score (HR = 1.05; 95%CI = 1.01–1.08), and two or more hospitalizations during screening period (HR = 1.19; 95%CI = 1.01–1.39), along with older age and male sex, were independently associated with the development of lung cancer. Conclusion Our data suggest that the development of lung cancer is not independently associated with inhaler prescription, but with coexisting DILD, a higher Charlson Comorbidity Index score, and frequent hospitalization.

Abstract Differentiating clinical stages based solely on positive findings from amyloid PET is challenging. We aimed to investigate the neuroanatomical characteristics at the whole-brain level that differentiate prodromal Alzheimer’s disease (AD) from cognitively unimpaired amyloid-positive individuals (CU A+) in relation to amyloid deposition and regional atrophy. We included 45 CU A+ participants and 135 participants with amyloid-positive prodromal AD matched 1:3 by age, sex, and education. All participants underwent 18F-florbetaben positron emission tomography and 3D structural T1-weighted magnetic resonance imaging. We compared the standardized uptake value ratios (SUVRs) and volumes in 80 regions of interest (ROIs) between CU A+ and prodromal AD groups using independent t-tests, and employed the least absolute selection and shrinkage operator (LASSO) logistic regression model to identify ROIs associated with prodromal AD in relation to amyloid deposition, regional atrophy, and their interaction. After applying False Discovery Rate correction at

Abstract Objectives To assess whether a deep learning-based system (DLS) with black-blood imaging for brain metastasis (BM) improves the diagnostic workflow in a multi-center setting. Materials and methods In this retrospective study, a DLS was developed in 101 patients and validated on 264 consecutive patients (with lung cancer) having newly developed BM from two tertiary university hospitals, which performed black-blood imaging between January 2020 and April 2021. Four neuroradiologists independently evaluated BM either with segmented masks and BM counts provided (with DLS) or not provided (without DLS) on a clinical trial imaging management system (CTIMS). To assess reading reproducibility, BM count agreement between the readers and the reference standard were calculated using limits of agreement (LoA). Readers’ workload was assessed with reading time, which was automatically measured on CTIMS, and were compared between with and without DLS using linear mixed models considering the imaging center. Results In the validation cohort, the detection sensitivity and positive predictive value of the DLS were 90.2% (95% confidence interval [CI]: 88.1–92.2) and 88.2% (95% CI: 85.7–90.4), respectively. The difference between the readers and the reference counts was larger without DLS (LoA: −0.281, 95% CI: −2.888, 2.325) than with DLS (LoA: −0.163, 95% CI: −2.692, 2.367). The reading time was reduced from mean 66.9 s (interquartile range: 43.2–90.6) to 57.3 s (interquartile range: 33.6–81.0) (P

Background/Aims Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. Methods This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10–100 ng/mL, 100–500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. Results This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. Conclusion High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.

Abstract Background To evaluate the clinical significance of noninvasive prenatal testing (NIPT) for detecting fetal sex chromosome aneuploidies (SCAs) in Korean pregnant women. Methods We retrospectively analyzed NIPT data from 9,176 women with singleton pregnancies referred to the CHA Biotech genome diagnostics center. Cell-free fetal DNA (cffDNA) was extracted from maternal peripheral blood, and high-throughput massively parallel sequencing was conducted. Subsequently, the positive NIPT results for SCA were validated via karyotype and chromosomal microarray analyses. Results Overall, 46 cases were SCA positive after NIPT, including 20, 12, 8, and 6 for Turner, triple X, Klinefelter, and Jacob syndromes, respectively. Among 37 women with invasive prenatal diagnosis, 19 had true positive NIPT results. The overall positive predictive value (PPV) of NIPT for detecting SCAs was 51.35%. The PPV was 18.75% for Turner, 88.89% for triple X, 71.43% for Klinefelter, and 60.00% for Jacob’s syndromes. NIPT accuracy for detecting sex chromosome trisomies was higher than that for sex chromosome monosomy (P = 0.002). No significant correlation was observed between fetal SCA incidence and maternal age (P = 0.914), except for the borderline significance of Jacob’s syndrome (P = 0.048). No significant differences were observed when comparing NIPT and karyotyping validation for fetal SCA according to pregnancy characteristics. Conclusion Our data suggest that NIPT can reliably screen for SCAs, and it performed better in predicting sex chromosome trisomies compared with monosomy X. No correlation was observed between maternal age and fetal SCA incidence, and no association was observed between different pregnancy characteristics. The accuracy of these findings requires improvements; however, our study provides an important reference for clinical genetic counseling and further management. Larger scale studies, considering confounding factors, are required for accurate evaluation.

Rehabilitation training is essential for a successful recovery of upper extremity function after stroke. Training programs are typically conducted in hospitals or rehabilitation centers, supervised by specialized medical professionals. However, frequent visits to hospitals can be burdensome for stroke patients with limited mobility. We consider a self-administered rehabilitation system based on a mobile application in which patients can periodically upload videos of themselves performing reach-to-grasp tasks to receive recommendations for self-managed exercises or progress reports. Sensing equipment aside from cameras is typically unavailable in the home environment. A key contribution of our work is to propose a deep learning-based assessment model trained only with video data. As all patients carry out identical tasks, a fine-grained assessment of task execution is required. Our model addresses this difficulty by learning RGB and optical flow data in a complementary manner. The correlation between the RGB and optical flow data is captured by a novel module for modality fusion using cross-attention with Transformers. Experiments showed that our model achieved higher accuracy in movement assessment than existing methods for action recognition. Based on the assessment model, we developed a patient-centered, solution-based mobile application for upper extremity exercises for hemiplegia, which can recommend 57 exercises with three levels of difficulty. A prototype of our application was evaluated by potential end-users and achieved a good quality score on the Mobile Application Rating Scale (MARS).

Background Stenotrophomonas maltophilia has been increasingly recognized as an opportunistic pathogen associated with high morbidity and mortality. Data on the prognostic factors associated with S. maltophilia pneumonia in patients admitted to intensive care unit (ICU) are lacking. Methods We conducted a retrospective analysis of data from 117 patients with S. maltophilia pneumonia admitted to the ICUs of two tertiary referral hospitals in South Korea between January 2011 and December 2022. To assess risk factors associated with in-hospital mortality, multivariable logistic regression analyses were performed. Results The median age of the study population was 71 years. Ventilator-associated pneumonia was 76.1% of cases, and the median length of ICU stay before the first isolation of S. maltophilia was 15 days. The overall in-hospital mortality rate was 82.1%, and factors independently associated with mortality were age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.00–1.09; P=0.046), Sequential Organ Failure Assessment (SOFA) score (OR, 1.21; 95%; CI, 1.02–1.43; P=0.025), corticosteroid use (OR, 4.19; 95% CI, 1.26–13.91; P=0.019), and polymicrobial infection (OR, 0.22; P=0.009). However, the impact of appropriate antibiotic therapy on mortality was insignificant. In a subgroup of patients who received appropriate antibiotic therapy (n=58), antibiotic treatment modality-related variables, including combination or empirical therapy, also showed no significant association with survival. Conclusions Patients with S. maltophilia pneumonia in ICU have high mortality rates. Older age, higher SOFA score, and corticosteroid use were independently associated with increased in-hospital mortality, whereas polymicrobial infection was associated with lower mortality. The effect of appropriate antibiotic therapy on prognosis was insignificant.

Cystic fibrosis (CF) is a fatal hereditary disorder that primarily affects Caucasians and is rare in Asian populations, including Koreans. Diagnosing CF is often challenging and delayed owing to its rarity and its overlapping features with non-CF diseases, ultimately affecting the patient prognosis. Radiologists can provide initial clues for clinically unsuspected cases and play a crucial role in establishing an early childhood diagnosis. This pictorial essay reviews the clinical and imaging features of genetically confirmed CF in Korean children and increases awareness of this rare disease, thereby facilitating early diagnosis.

Abstract Objective The purpose of this study was to evaluate the prognostic impact of body composition parameters based on computed tomography (CT) in patients with non-small cell lung cancer (NSCLC) who received ICI treatment. Methods This retrospective study analyzed the data from advanced NSCLC patients treated with ICI therapy between 2013 and 2019. We included patients with NSCLC who underwent baseline CT scans. The exclusion criteria included patients who received three or more lines of chemotherapy, those with insufficient clinical information, or those without treatment response evaluation. Results A total of 136 patients were enrolled. Among the volumetric body composition parameters, patients in the highest quartiles (Q2–4) of the visceral fat index (VFI) exhibited a higher response rate to ICI therapy than those in the lowest quartile (Q1) of VFI (Q1 vs. Q2–4: 18.2% vs. 43.1%, p = 0.012). Patients with a VFI in Q2–4 had significantly prolonged progression-free survival (PFS) and overall survival (OS) (PFS, Q1 vs. Q2–4: 3.0 months vs. 6.4 months, p = 0.043; OS, Q1 vs. Q2–4: 5.6 months vs. 16.3 months, p = 0.004). Kaplan–Meier analysis based on the VFI and visceral fat Hounsfield unit (HU) revealed that patients with VFI in Q1 and HU in Q2–4 had the worst prognosis. Conclusions Visceral fat volume is significantly associated with treatment outcomes in ICI-treated patients with NSCLC. Moreover, fat quality may impact the treatment outcomes. This finding underscores the potential significance of both fat compartments and fat quality as prognostic indicators. Critical relevance statement Visceral fat volume is significantly associated with treatment outcomes in ICI-treated patients with non-small cell lung cancer. Moreover, fat quality may impact the treatment outcomes. This finding underscores the potential significance of both fat compartments and fat quality as prognostic indicators. Graphical Abstract Key points • We found that visceral fat volume positively correlated with treatment response and survival in patients with non-small cell lung cancer receiving immune checkpoint inhibitors. • Additionally, a trend toward a negative correlation between visceral fat attenuation and survival was observed. • The findings highlight the prognostic utility of fat compartments and fat quality.

Abstract Background Accurate response parameters are important for patients with brain metastasis (BM) undergoing clinical trials using immunotherapy, considering poorly defined enhancement and variable responses. This study investigated MRI-based surrogate endpoints for patients with BM receiving immunotherapy. Methods Sixty-three non-small cell lung cancer patients with BM who received immune checkpoint inhibitors and underwent MRI were included. Tumor diameters were measured using a modification of the RECIST 1.1 (mRECIST), RANO-BM, and iRANO adjusted for BM (iRANO-BM). Tumor volumes were segmented on 3D contrast-enhanced T1-weighted imaging. Differences between the sum of the longest diameter (SLD) or total tumor volume at baseline and the corresponding measurement at time of the best overall response were calculated as “changes in SLDs” (for each set of criteria) and “change in volumetry,” respectively. Overall response rate (ORR), progressive disease (PD) assignment, and progression-free survival (PFS) were compared among the criteria. The prediction of overall survival (OS) was compared between diameter-based and volumetric change using Cox proportional hazards regression analysis. Results The mRECIST showed higher ORR (30.1% vs. both 17.5%) and PD assignment (34.9% vs. 25.4% [RANO-BM] and 19% [iRANO-BM]). The iRANO-BM had a longer median PFS (13.7 months) than RANO-BM (9.53 months) and mRECIST (7.73 months, P = 0.003). The change in volumetry was a significant predictor of OS (HR = 5.87, 95% CI: 1.46–23.64, P = 0.013). None of the changes in SLDs, as determined by RANO-BM or iRANO-BM, were significant predictors of OS, except for the mRECIST, which exhibited a weak association with OS. Conclusion Quantitative volume measurement may be an accurate surrogate endpoint for OS in patients with BM undergoing immunotherapy, especially considering the challenges of multiplicity and the heterogeneity of sub-centimeter size responses.

Abstract Temporal parameters during swallowing are analyzed for objective and quantitative evaluation of videofluoroscopic swallowing studies (VFSS). Manual analysis by clinicians is time-consuming, complicated and prone to human error during interpretation; therefore, automated analysis using deep learning has been attempted. We aimed to develop a model for the automatic measurement of various temporal parameters of swallowing using deep learning. Overall, 547 VFSS video clips were included. Seven temporal parameters were manually measured by two physiatrists as ground-truth data: oral phase duration, pharyngeal delay time, pharyngeal response time, pharyngeal transit time, laryngeal vestibule closure reaction time, laryngeal vestibule closure duration, and upper esophageal sphincter opening duration. ResNet3D was selected as the base model for the deep learning of temporal parameters. The performances of ResNet3D variants were compared with those of the VGG and I3D models used previously. The average accuracy of the proposed ResNet3D variants was from 0.901 to 0.981. The F1 scores and average precision were 0.794 to 0.941 and 0.714 to 0.899, respectively. Compared to the VGG and I3D models, our model achieved the best results in terms of accuracy, F1 score, and average precision values. Through the clinical application of this automatic model, temporal analysis of VFSS will be easier and more accurate.

Plants of the Asteraceae family have been cultivated worldwide for economic, medicinal, and ornamental purposes, including genera such as Aster, Helianthus, and Cosmos. Numerous studies examined their secondary metabolites; however, those of Aster × chusanensis, which is a natural hybrid species in South Korea, are unclear, and optimized propagation methods should be identified. We analyzed phenolic acid concentrations in each part of Aster × chusanensis through HPLC. Further, we investigated the growth characteristics and secondary metabolite concentrations under various growth temperatures using division propagation, followed by growing at 20, 25, and 30 °C in a growth chamber. Chlorogenic acid was the primary compound, which was particularly high in the leaves. The growth characteristics did not differ significantly between temperatures, and 30 °C was most efficient for phenolic acid biosynthesis. Our results provide valuable information on optimized propagation and secondary metabolite concentrations under different temperatures of Aster × chusanensis.

Abstract Background Necroptosis is a regulated inflammatory cell death which plays a significant role in cancer development and progression. In this study, we evaluated whether genetic variants in key regulators of necroptosis may affect survival outcome of non‐small cell lung cancer (NSCLC) patients after surgical resection. Methods A total of 674 patients who underwent curative surgery were included. Fifteen genetic variants in key regulators of necroptosis (RIPK1, RIPK3, and MLKL) were selected. The association of these variants with survival outcomes was evaluated. Results Two variants, RIPK1 rs17548629C > T and MLKL rs877375G > C, were associated with better overall survival and disease‐free survival in multivariate analyses. When the patients were divided according to histology, the associations were significant only in adenocarcinoma, but not in squamous cell carcinoma. RIPK1 rs17548629 C‐to‐T change was associated with significantly increased luciferase activity by modulating the binding of miR‐642a. Promoter assays showed a significantly increased promoter activity in MLKL rs877375C allele compared to G allele. Consistently, the mRNA expression level of RIPK1 and MLKL showed significant positive correlation with RIPK1 rs17548629C‐to‐T and MLKL rs877375G‐to‐C changes. Conclusion Two genetic variants in key regulators in necroptosis, RIPK1 rs17548629C > T and MLKL rs877375G > C, may be used as biomarkers to predict survival outcomes in surgically resected NSCLC patients.

Abstract Introduction Non‐small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation has a higher incidence of brain metastases than wild‐type EGFR mutations. Osimertinib, a third‐generation EGFR tyrosine kinase inhibitor (TKI), targets both EGFR‐TKI sensitizing and T790M‐resistance mutations and has a higher brain penetration rate relative to first‐ and second‐generation EGFR‐TKIs. Therefore, osimertinib has become a preferred first‐line therapy for advanced EGFR mutation‐positive NSCLC. However, lazertinib, an emerging EGFR‐TKI, has shown higher selectivity toward EGFR mutations and improved penetration of the blood–brain barrier compared to osimertinib in preclinical studies. This trial will evaluate the efficacy of lazertinib as a first‐line therapy in patients with EGFR mutation‐positive NSCLC who have brain metastases, with or without additional local therapy. Methods This is a single‐center, open‐label, single‐arm phase II trial. A total of 75 patients with advanced EGFR mutation‐positive NSCLC will be recruited. Eligible patients will receive oral lazertinib 240 mg, once daily until disease progression or intolerable toxicity is detected. Patients with moderate to severe symptoms related to brain metastasis will simultaneously receive local therapy for the brain. The primary endpoints are progression‐free survival and intracranial progression‐free survival. Discussion Lazertinib, in combination with local therapy for the brain, if necessary, is expected to improve the clinical benefit in advanced EGFR mutation‐positive NSCLC with brain metastases, as a first‐line treatment.

Abstract Purpose To address the limited utility of the interferon (IFN)-γ release assay (IGRA) caused by its variability and inconsistency. Methods This retrospective cohort study was based on data obtained between 2011 and 2019. QuantiFERON-TB Gold-In-Tube was used to measure IFN-γ levels in nil, tuberculosis (TB) antigen, and mitogen tubes. Results Of 9,378 cases, 431 had active TB. The non-TB group comprised 1,513 IGRA-positive, 7,202 IGRA-negative, and 232 IGRA-indeterminate cases. Nil-tube IFN-γ levels were significantly higher in the active TB group (median = 0.18 IU/mL; interquartile range: 0.09–0.45 IU/mL) than in the IGRA-positive non-TB (0.11 IU/mL; 0.06–0.23 IU/mL) and IGRA-negative non-TB (0.09 IU/mL; 0.05–0.15 IU/mL) groups (P < 0.0001). From receiver operating characteristic analysis, TB antigen tube IFN-γ levels had higher diagnostic utility for active TB than TB antigen minus nil values. In a logistic regression analysis, active TB was the main driver of higher nil values. In the active TB group, after reclassifying the results based on a TB antigen tube IFN-γ level of 0.48 IU/mL, 14/36 cases with negative results and 15/19 cases with indeterminate results became positive, while 1/376 cases with positive results became negative. Overall, the sensitivity for detecting active TB improved from 87.2 to 93.7%. Conclusion The results of our comprehensive assessment can aid in IGRA interpretation. Since nil values are governed by TB infection rather than reflecting background noise, TB antigen tube IFN-γ levels should be used without subtracting nil values. Despite indeterminate results, TB antigen tube IFN-γ levels can be informative.

Abstract The purpose of this study was to clarify the association between improvement of spasticity in hemiplegic patient’s upper extremity with Botulinum toxin injection and improvement in postural balance and gait function. For this prospective cohort study, sixteen hemiplegic stroke patients with upper extremity spasticity were recruited. The plantar pressure with gait parameters, postural balance parameters, Modified Ashworth Scale, and Modified Tardieu Scale were evaluated before, 3 weeks and 3 months after Botulinum toxin A (BTxA) injection. Spasticity of hemiplegic upper extremity before, and after BTxA injection were significantly changed. Plantar pressure overload in affected side was reduced after BTxA injection. The mean X-speed and the horizontal distance decreased in postural balance analysis with eyes-opened test. Improvement in hemiplegic upper extremity spasticity showed positive correlation with gait parameters. In addition, improvement in hemiplegic upper extremity spasticity was positively correlated with change in balance parameters in postural balance analysis with eyes-closed and dynamic tests. This study focused on the effect of stroke patient’s hemiplegic upper extremity spasticity on their gait and balance parameters and identified that the BTxA injection on hemiplegic patient’s spastic upper extremity improve postural balance and gait function.

Abstract Background Neurogenic differentiation factor 1 (NEUROD1) is frequently overexpressed in small‐cell lung cancer (SCLC). NEUROD1 plays an important role in promoting malignant behavior and survival. Methods In this study, we evaluated the association between putative functional polymorphisms in 45 NEUROD1 target genes and chemotherapy response and survival outcomes in 261 patients with SCLC. Among the 100 single nucleotide polymorphisms (SNPs) studied, two were significantly associated with both chemotherapy response and overall survival (OS) of patients with SCLC. Results The SNP rs3806915C>A in semaphorin 6A (SEMA6A) gene was significantly associated with better chemotherapy response and OS (p = 0.04 and p = 0.04, respectively). The SNP rs11265375C>T in nescient helix–loop helix 1 (NHLH1) gene was also associated with better chemotherapy response and OS (p = 0.04 and p = 0.02, respectively). Luciferase assay showed a significantly higher promoter activity of SEMA6A with the rs3806915 A allele than C allele in H446 lung cancer cells (p = 4 × 10−6). The promoter activity of NHLH1 showed a significantly higher with the rs11265375 T allele than C allele (p = 0.001). Conclusion These results suggest that SEMA6A rs3806915C>A and NHLH1 rs11265375C>T polymorphisms affect the promoter activity and expression of the genes, which may affect the survival outcome of patients with SCLC.

IntroductionThe global adoption of the “freeze-all strategy” has led to a continuous increase in utilization of single vitrified-warmed blastocyst embryo transfer (SVBT) owing to its clinical effectiveness. Accurate prediction of clinical pregnancy is crucial from a patient-centered perspective. However, this remains challenging, with inherent limitations due to the absence of precise and user-friendly prediction tools. Thus, this study primarily aimed to develop and assess a nomogram based on quantitative clinical data to optimize the efficacy of personalized prognosis assessment.Materials and methodsWe conducted a retrospective cohort analysis of ongoing pregnancy data from 658 patients with infertility who underwent SVBT at our center between October 17, 2017, and December 18, 2021. Patients were randomly assigned to the training (n=461) or validation (n=197) cohort for nomogram development and testing, respectively. A nomogram was constructed using the results of the multivariable logistic regression (MLR), which included clinical covariates that were assessed for their association with ongoing pregnancy.ResultsThe MLR identified eight significant variables that independently predicted ongoing pregnancy outcomes in the study population. These predictors encompassed maternal physiology, including maternal age at oocyte retrieval and serum anti-Müllerian hormone levels; uterine factors, such as adenomyosis; and various embryo assessment parameters, including the number of fertilized embryos, blastocyst morphology, blastulation day, blastocyst re-expansion speed, and presence of embryo string. The area under the receiver operating characteristic curve in our prediction model was 0.675 (95% confidence interval [CI], 0.622–0.729) and 0.656 (95% CI, 0.573–0.739) in the training and validation cohorts, respectively, indicating good discrimination performance in both cohorts.ConclusionsOur individualized nomogram is a practical and user-friendly tool that can provide accurate and useful SVBT information for patients and clinicians. By offering this model to patients, clinical stakeholders can alleviate uncertainty and confusion about fertility treatment options and enhance patients’ confidence in making informed decisions.

Abstract Background Recurrence is common in glioblastoma multiforme (GBM) because of the infiltrative, residual cells in the tumor margin. Standard therapy for GBM consists of surgical resection followed by chemotherapy and radiotherapy, but the median survival of GBM patients remains poor (~ 1.5 years). For recurrent GBM, anti-angiogenic treatment is one of the common treatment approaches. However, current anti-angiogenic treatment modalities are not satisfactory because of the resistance to anti-angiogenic agents in some patients. Therefore, we sought to identify novel prognostic biomarkers that can predict the therapeutic response to anti-angiogenic agents in patients with recurrent glioblastoma. Methods We selected patients with recurrent GBM who were treated with anti-angiogenic agents and classified them into responders and non-responders to anti-angiogenic therapy. Then, we performed proteomic analysis using liquid-chromatography mass spectrometry (LC–MS) with formalin-fixed paraffin-embedded (FFPE) tissues obtained from surgical specimens. We conducted a gene-ontology (GO) analysis based on protein abundance in the responder and non-responder groups. Based on the LC–MS and GO analysis results, we identified potential predictive biomarkers for anti-angiogenic therapy and validated them in recurrent glioblastoma patients. Results In the mass spectrometry-based approach, 4957 unique proteins were quantified with high confidence across clinical parameters. Unsupervised clustering analysis highlighted distinct proteomic patterns (n = 269 proteins) between responders and non-responders. The GO term enrichment analysis revealed a cluster of genes related to immune cell-related pathways (e.g., TMEM173, FADD, CD99) in the responder group, whereas the non-responder group had a high expression of genes related to nuclear replisome (POLD) and damaged DNA binding (ERCC2). Immunohistochemistry of these biomarkers showed that the expression levels of TMEM173 and FADD were significantly associated with the overall survival and progression-free survival of patients with recurrent GBM. Conclusions The candidate biomarkers identified in our protein analysis may be useful for predicting the clinical response to anti-angiogenic agents in patients with recurred GBM.

Abstract In brain magnetic resonance imaging (MRI), white matter hyperintensity (WMH) is a commonly encountered finding and is known to reflect cerebral small vessel disease. The aim of our study was to investigate the association of coronary artery calcium (CAC) with WMH and elucidate the relationship between WMH and atherosclerotic risk factors in a large-scale healthy population. This retrospective study included 1337 individuals who underwent brain MRI and CAC scoring computed tomography at healthcare centers affiliated with a tertiary hospital. Cerebral WMH was defined as Fazekas score greater than 2 on brain MRI. Intracranial artery stenosis (ICAS) was also assessed and determined to be present when stenosis was more than 50% on angiography. The associations of risk factors, CAC score, and ICAS with cerebral WMH were assessed by multivariable regression analysis. In multivariable analysis, categories of higher CAC scores showed increased associations with both periventricular and deep WMHs in a dose-dependent relationship. The presence of ICAS was also significantly related to cerebral WMH, and among the clinical variables, age and hypertension were independent risk factors. In conclusion, CAC showed a significant association with cerebral WMH in a healthy population, which might provide evidence for referring to the CAC score to identify individuals with risk of cerebral WMH.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

Abstract This study was conducted to investigate the relationship between genetic variants in LKB1/AMPK/mTOR pathway and treatment outcomes of patients with non‐small cell lung cancer (NSCLC) treated with chemotherapy. A total of 379 patients with NSCLC who underwent first‐line paclitaxel‐cisplatin chemotherapy was enrolled. The associations between 19 single nucleotide variants (SNVs) in the LKB1/AMPK/mTOR pathway and the chemotherapy response and overall survival (OS) were analyzed. Among the SNVs analyzed, AKT1 rs2494750G>C and TSC1 rs2809244C>A were associated with clinical outcomes after chemotherapy in multivariate analyses. The AKT1 rs2494750G>C was significantly associated with a better response to chemotherapy (adjusted odds ratio [aOR]: 1.92, 95% confidence interval [CI]: 1.02–3.62, p = 0.04). The TSC1 rs2809244C>A were significantly associated with better OS (adjusted hazard ratio [aHR]: 0.79, 95% CI: 0.62–0.99, p = 0.04). When stratified by tumor histology, AKT1 rs2494750G>C exhibited a significant association with the chemotherapy response only in adenocarcinoma and TSC1 rs2809244C>A was also significantly associated with OS only in adenocarcinoma. This result suggests that the AKT1 rs2494750G>C and TSC1 rs2809244 C>A may be useful for predicting the clinical outcome of first‐line paclitaxel‐cisplatin chemotherapy in NSCLC.

Periventricular nodular heterotopia (PNH) is a neuronal migration disorder that occurs during early brain development. Patients with PNH may be asymptomatic and have normal intelligence; however, PNH is also known to cause various symptoms such as seizures, dyslexia, and cardiovascular anomalies. PNH is not commonly diagnosed during early infancy because of the lack of clinical manifestations during this period. We present the case of a female infant diagnosed with PNH based on brain magnetic resonance imaging, who had symptomatic patent ductus arteriosus that had to be ligated surgically and had prolonged feeding cyanosis with frequent apneic spells.

Abstract Background Understanding the changes in characteristics of patients who visited trauma centres during the coronavirus disease 2019 (COVID-19) pandemic is important to facilitate aneffective response. This retrospective study was conducted to analyse differences in the characteristics and outcomes of patients who visited our trauma centre between pre-COVID-19 and COVID-19 eras. Methods Medical data of trauma patients enrolled in the Korean trauma database from 1 January 2018 to 31 August 2021 were collected. The number of trauma centre visits, patient characteristics, factors associated with in-hospital intervention, and outcomes werecompared between patients in the two time periods. Propensity score matching was performed to analyse the outcomes in patients with similar characteristics and severitybetween patients in the two time periods. Results The number of emergency department (ED) trauma service visits reduced in the COVID-19 era. Based on the mean age, the patients were older in the COVID-19 era. Abbreviated injury scale (AIS) 1, AIS3, AIS5, and injury severity score (ISS) were higher in the COVID-19 era. The proportion of motor vehicle collisions decreased, whereas falls increased during the COVID-19 era. Ambulance transportation, admission to the general ward, and time from injury to ED visit significantly increased. Patient outcomes, such as hospital length of stay (LOS), intensive care unit (ICU) LOS, and duration of mechanical ventilation improved, while injury severity worsened during the COVID-19 era. After adjusting for patient characteristics and severity, similar findings were observed. Conclusion The small reduction in the number of trauma patients and visits by patients who hadhigher ISS during the COVID-19 pandemic highlights the importance of maintaining trauma service capacity and capability during the pandemic. A nationwide or nationalmulticentre study will be more meaningful to examine the impact of the COVID-19 outbreak on the changes in trauma patterns, volume, and patient outcomes.

Presumed idiopathic intracranial hypertension (IIH) is a disorder of elevated intracranial pressure with unknown etiology, and 10% of cases occur secondarily to cerebral venous sinus thrombosis (CVST). CVST may be underestimated when findings of IIH are missed in a normal-weight patient without risk factors of coagulopathy. Here, we present a case of CVST that mimics a neurogenic tumor in the hypoglossal canal in a normal-weight patient without risk factors of coagulopathy.

Abstract Raman spectroscopic-based biosensing strategies are often complicated by low signal and the presence of multiple chemical species. While surface-enhanced Raman spectroscopy (SERS) nanostructured platforms are able to deliver high quality signals by focusing the electromagnetic field into a tight plasmonic hot-spot, it is not a generally applicable strategy as it often depends on the specific adsorption of the analyte of interest onto the SERS platform. This paper describes a strategy to address this challenge by using surface potential as a physical binding agent in the context of microneedle sensors. We show that the potential-dependent adsorption of different chemical species allows scrutinization of the contributions of different chemical species to the final spectrum, and that the ability to cyclically adsorb and desorb molecules from the surface enables efficient application of multivariate analysis methods. We demonstrate how the strategy can be used to mitigate potentially confounding phenomena, such as surface reactions, competitive adsorption and the presence of molecules with similar structures. In addition, this decomposition helps evaluate criteria to maximize the signal of one molecule with respect to others, offering new opportunities to enhance the measurement of analytes in the presence of interferants.

Abstract Developing a high‐performance anode design is important for a low‐cost proton‐exchange membrane water electrolyzer (PEMWE). In this study, an iridium nickel oxide directly coated anode (IrNiOx electrode) for high‐efficient PEMWE is reported. Five IrNiOx electrodes with different Ir‐to‐Ni ratios are developed using co‐electrodeposition. The resulting electrodes contain a thin IrNiOx layer on the carbon substrate. To develop the PEMWE incorporating IrNiOx electrode, the effect of fabrication methods, catalyst compositions, and porous transport layer are investigated. Consequently, the IrNiOx electrode prepared with 7:3 precursor solution (Ir0.5Ni0.5Ox) exhibits higher oxygen evolution reaction activity with a smaller overpotential than the electrode prepared with 10:0 precursor solution (IrOx) and the commercial IrO2. Furthermore, the performance of the PEMWE is higher with the Ir0.5Ni0.5Ox electrode than that with the sprayed electrode with commercial IrO2 nanoparticles. This enhancement is attributed to the high electrochemical surface area caused by introducing Ni in IrOx. Additionally, the performance of the directly coated Ir0.5Ni0.5Ox PEMWE is the highest reported in the literature.

We investigated the safety and efficacy of pemetrexed monotherapy in patients with lung adenocarcinoma and various renal conditions, including chronic kidney disease. We also analyzed whether baseline renal function affected progression-free survival (PFS). We retrospectively analyzed 71 patients who received maintenance-and second-line pemetrexed monotherapy. Patients were divided into two groups according to estimated glomerular filtration rate (eGFR): fair eGFR (>60 mL/min/1.73 m2) and lower eGFR (59 mL/min/1.73 m2 or less). The safety and efficacy were evaluated for each group. Median ages were 73.2 years in the lower eGFR group (n=28) and 64.5 years in the fair eGFR group (n=43). Patients with a lower eGFR achieved a median PFS of 4.7 months, while the median PFS for patients with a fair eGFR was 2.7 months. The difference between the two groups was not statistically significant (p=0.075). Both groups showed treatment-related low-grade hematological and non-hematological adverse events. Pemetrexed monotherapy is safe and effective in patients with lung adenocarcinoma with a lower eGFR.

Purpose: To investigate the diffusion-weighted imaging (DWI) findings and apparent diffusion coefficient (ADC) value of the thymus in children under the age of 13 who have non-thymic neoplasms. Materials and Methods: From January 2021 to April 2023, a single-center retrospective study analyzed consecutive 191 thoracic MRI scans with DWI from 67 children (Results: Forty-five percent (86/191) of the scans exhibited restricted diffusion in the thymus: multifocal (n = 65; 76%), focal (n = 19; 22%), and diffuse (n = 2; 2%) patterns. The restricted diffusion group demonstrated higher absolute lymphocyte counts, more prominent thymus sizes, and higher frequency of off-treatment status compared to the unrestricted diffusion group (p>0.05). The mean ADC value across all 191 scans was 1.80 × 10−3 mm2/s. No significant difference was observed in the ADC value related to restricted diffusion patterns, the MRI vendors, or the age at the time of the scan. Conclusions: Restricted diffusion was observed in 45% of the thymus in children with non-thymic neoplasms, with a mean ADC value of 1.80 × 10−3 mm2/s. Recognizing the DWI findings can prevent unnecessary invasive procedures, alleviating concerns for patients and families.

Discontinuing mechanical ventilation remains challenging. We developed a machine learning model to predict weaning outcomes using only continuous monitoring parameters obtained from ventilators during spontaneous breathing trials (SBTs). Patients who received mechanical ventilation in the medical intensive care unit at a tertiary university hospital from 2019–2021 were included in this study. During the SBTs, three waveforms and 25 numerical data were collected as input variables. The proposed convolutional neural network (CNN)-based weaning prediction model extracts features from input data with diverse lengths. Among 138 enrolled patients, 35 (25.4%) experienced weaning failure. The dataset was randomly divided into training and test sets (8:2 ratio). The area under the receiver operating characteristic curve for weaning success by the prediction model was 0.912 (95% confidence interval [CI], 0.795–1.000), with an area under the precision-recall curve of 0.767 (95% CI, 0.434–0.983). Furthermore, we used gradient-weighted class activation mapping technology to provide visual explanations of the model’s prediction, highlighting influential features. This tool can assist medical staff by providing intuitive information regarding readiness for extubation without requiring any additional data collection other than SBT data. The proposed predictive model can assist clinicians in making ventilator weaning decisions in real time, thereby improving patient outcomes.

In vivo oocytes grow and mature in ovarian follicles whereas oocytes are matured in vitro in plastic culture dishes with a hard surface. In vivo oocytes show a superior developmental ability to in vitro counterparts, indicating suboptimal environments of in vitro culture. This study aimed to evaluate the influence of an agarose matrix as a culture substrate during in vitro maturation (IVM) on the development of pig oocytes derived from small antral follicles (SAFs). Cumulusoocyte complexes (COCs) retrieved from SAFs were grown in a plastic culture dish without an agarose matrix and then cultured for maturation in a plastic dish coated without (control) or with a 1% or 2% (w/v) agarose hydrogel. Then, the effect of the soft agarose matrix on oocyte maturation and embryonic development was assessed by analyzing intra-oocyte contents of glutathione (GSH) and reactive oxygen species (ROS), expression of VEGFA, HIF1A, and PFKP genes, and blastocyst formation after parthenogenesis. IVM of pig COCs on a 1% (w/v) agarose matrix showed a significantly higher blastocyst formation, intra-oocyte GSH contents, and transcript abundance of VEGFA. Moreover, a significantly lower intra-oocyte ROS content was detected in oocytes matured on the 1% and 2% (w/v) agarose matrices than in control. Our results demonstrated that IVM of SAFs-derived pig oocytes on a soft agarose matrix enhanced developmental ability by improving the cytoplasmic maturation of oocytes through redox balancing and regulation of gene expression.

Purpose The purpose of this study was to use shear-wave elastography (SWE) to assess testicular stiffness changes during the Valsalva maneuver in adolescents and young adults with varicocele, to compare these changes according to clinical severity, and to evaluate the role of SWE in the diagnosis of varicocele. Methods This study included patients undergoing testicular ultrasonography for the diagnosis of varicocele or for post-varicocelectomy follow-up between June 2016 and February 2017. Fifty-four testicles of 27 consecutive patients (mean age, 15.9 years) were classified by clinical grade (grade 0-3). Using SWE, mean testicular stiffness (Emean) was measured at rest and during the Valsalva maneuver. The correlations between multiple ultrasonographic parameters (volume asymmetry, Emean at rest, and absolute and percentage changes in Emean during the Valsalva maneuver) and clinical grade were assessed using the Spearman correlation test. Results The Emean at rest was similar across clinical grades. During the Valsalva maneuver, increased testicular stiffness was frequently observed in patients with grade 2 or 3 varicocele but rarely observed in those with grade 0 or 1 varicocele. The changes in Emean were positively correlated with the clinical grade (all P0.05). Conclusion A transient, reversible increase in testicular stiffness during the Valsalva maneuver was observed in adolescents with high-grade varicocele, and the degree of stiffness change was correlated with the clinical grade. Stiffness change identified using SWE during the Valsalva maneuver is a potential surrogate indicator of venous congestion.

Background/Aims Pleural fluid adenosine deaminase (ADA) levels are useful in discriminating tuberculous pleural effusions (TPEs) from malignant pleural effusions (MPEs). However, some patients with MPE exhibit high-ADA levels, which may mimic TPEs. There is limited data regarding the differential diagnosis between high-ADA MPE and high-ADA TPE. This study aimed to identify the predictors for distinguishing high-ADA MPEs from high-ADA TPEs. Methods Patients with TPE and MPE with pleural fluid ADA levels ≥ 40 IU/L were included in this study. Clinical, laboratory, and radiological data were compared between the two groups. Independent predictors and their diagnostic performance for high-ADA MPEs were evaluated using multivariate logistic regression analysis and receiver operating characteristic curve. Results A total of 200 patients (high-ADA MPE, n = 30, and high-ADA TPE, n = 170) were retrospectively included. In the multivariate analysis, pleural fluid ADA, pleural fluid carcinoembryonic antigen (CEA), and pleural nodularity were independent discriminators between high-ADA MPE and high-ADA TPE groups. Using pleural ADA level of 40 to 56 IU/L (3 points), pleural CEA level ≥ 6 ng/mL (6 points), and presence of pleural nodularity (3 points) for predicting high-ADA MPEs, a sum score ≥ 6 points yielded a sensitivity of 90%, specificity of 96%, positive predictive value of 82%, negative predictive value of 98%, and area under the receiver operating characteristic curve of 0.965. Conclusions A scoring system using three parameters may be helpful in guiding the differential diagnosis between high-ADA MPEs and high-ADA TPEs.

Herein, we report two rare cases of renal infection. The first case was renal subcapsular urine reflux in a 8-month-old girl with recurrent urinary tract infection and the second was subcapsular abscess in a 14-year-old girl with diabetes, who was successfully treated with percutaneous drainage. It has been suggested that renal subcapsular abscesses could be caused by the direct reflux of urine into the subcapsular space, rather than spread of infection from an existing parenchymal lesion, and that complete recovery can be achieved if percutaneous drainage is performed in a timely manner. We propose primary subcapsular reflux, in which urine directly refluxes upwards into the subcapsular space of the kidney, as one of the mechanisms for development of renal subcapsular abscesses.

Background: Premature ovarian insufficiency (POI) is defined as the onset of a menopausal state prior to 40 years of age. Of the various causes of POI, genetic abnormalities account for 10.8% of all cases, which can be categorized into either chromosomal or gene anomalies. Chromosomal abnormalities of the isochromosome Xq [i(Xq)] type have been recognized as common causes of POI. Cases: A 16-year-old female presented with secondary amenorrhea that had persisted for one year. Her physical examination was unremarkable, including a height of 158 cm and the presence of secondary sexual characteristics. Her serum level of follicle-stimulating hormone was elevated (66 mIU/mL), whereas her estradiol and anti-Müllerian hormone levels were decreased (

The Radiation Therapy Oncology Group (RTOG) 9310 protocol clinical trial established high-dose methotrexate (HDMTX) as the standard for primary central nervous system lymphoma (PCNSL). We aimed to investigate the RTOG 9310 protocol’s PCNSL outcomes by examining progression-free survival (PFS) and overall survival (OS) rates and determining the influential factors. Between 2007 and 2020, 87 patients were histopathologically diagnosed with PCNSL and treated with the RTOG 9310 protocol. All received HDMTX 2.5 g/m2 and vincristine 1.4 mg/m2/day for 1 day during weeks 1, 3, 5, 7, and 9, and procarbazine 100 mg/m2/day for 1 day during weeks 1, 5, and 9. Dexamethasone was administered on a standard tapering schedule from the first week to the sixth week. Whole brain radiotherapy (WBRT), consisting of 45 Gy for patients with less than a complete response to the chemotherapy or 36 Gy for complete responders, was started 1 week after the last dose of chemotherapy was administered. Within three weeks of the completion of WBRT, patients received two courses of cytarabine, which were separated by 3–4 weeks. Clinical, radiological, and histopathological characteristics were retrospectively reviewed. All patients completed five HDMTX cycles and a mean follow-up of 60.2 (range, 6–150) months. Twenty-eight (32.2%) patients experienced recurrence during follow-up. The mean time to recurrence was 21.8 months, while the mean PFS was 104.3 (95% confidence interval (CI), 90.6–118.0) months. Eleven (12.6%) patients died; the mean OS was 132.1 (95% CI, 122.2–141.9) months. The 3- and 5-year survival rates were 92.0% and 87.4%, respectively. One patient experienced acute renal failure, while the remainder tolerated any cytotoxic side effects. On multivariate analysis, the Eastern Cooperative Oncology Group performance score ≤ 2; the International Extranodal Lymphoma Study Group low-risk status; XBP-1, p53, and c-Myc negativity; homogenous enhancement; gross total resection, independently correlated with long PFS and OS. The RTOG 9310 protocol is effective for PCNSL and features good outcomes.

Abstract Even a tiny functioning pituitary adenoma could cause symptoms; hence, accurate diagnosis and treatment are crucial for management. However, it is difficult to diagnose a small pituitary adenoma using conventional MR sequence. Deep learning-based reconstruction (DLR) using magnetic resonance imaging (MRI) enables high-resolution thin-section imaging with noise reduction. In the present single-institution retrospective study of 201 patients, conducted between August 2019 and October 2020, we compared the performance of 1 mm DLR MRI with that of 3 mm routine MRI, using a combined imaging protocol to detect and delineate pituitary adenoma. Four readers assessed the adenomas in a pairwise fashion, and diagnostic performance and image preferences were compared between inexperienced and experienced readers. The signal-to-noise ratio (SNR) was quantitatively assessed. New detection of adenoma, achieved using 1 mm DLR MRI, was not visualised using 3 mm routine MRI (overall: 6.5% [13/201]). There was no significant difference depending on the experience of the readers in new detections. Readers preferred 1 mm DLR MRI over 3 mm routine MRI (overall superiority 56%) to delineate normal pituitary stalk and gland, with inexperienced readers more preferred 1 mm DLR MRI than experienced readers. The SNR of 1 mm DLR MRI was 1.25-fold higher than that of the 3 mm routine MRI. In conclusion, the 1 mm DLR MRI achieved higher sensitivity in the detection of pituitary adenoma and provided better delineation of normal pituitary gland than 3 mm routine MRI.

Abstract To evaluate the association between thyroid echogenicity and heterogeneity seen on ultrasonography (US) and thyroid function in pediatric and adolescent populations with autoimmune diffuse thyroid diseases (AITD). From 2000 to 2020, we reviewed thyroid ultrasound (US) images and thyroid function statuses in 133 children and adolescent AITD patients. Our review of the images focused on decreased echogenicity and heterogeneity, which were classified into four grades. Among patients with overt hypothyroidism or overt hyperthyroidism, 94.2% (65/69) showed a US grade of 3 or 4. In patients with subclinical hyper/hypothyroidism or euthyroidism, 45.3% (29/64) showed grades 1 or 2. There were no overt hyper/hypothyroidism patients with US grade 1. When we compared US grades according to thyroid status, more severe thyroid dysfunction was significantly associated with higher US grade (p = 0.047). Thyroid stimulating hormone (TSH) level differed significantly according to US grades when we evaluated hyperthyroid (p = 0.035) and hypothyroid (p = 0.027) states independently. 11 patients showed both US grade and thyroid function status changes on follow-up US. In children and adolescent AITD patients, there was an association between decreased echogenicity and heterogeneity on US and thyroid dysfunction.