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Background: Primary ovarian insufficiency (POI) is one of the leading female infertility diseases in which ovarian function stops before the age of 40. Reports that POI is associated with transforming growth factor (TGF)-β/bone morphogenetic protein (BMP) signaling pathway–associated genes (e.g., TGF-β, and BMP15) have been continuous since publication that the TGF-β superfamily acts as important regulators for ovary and placenta function in humans. Mechanistically, the secretion of follicle-stimulating hormone, progesterone, and estrogen is affected by the TGF-β superfamily in granulosa cells, which are involved in the development of theca cells, oocytes, and granulosa cells. Objective: This study aimed to identify the association between genes related to the TGF-β/BMP signaling pathway and the risk of POI pathogenesis. Methods: Possible associations between six gene polymorphisms and POI susceptibility were examined in 139 patients with POI and 345 control subjects. Results: Allele combination of TGFBR1 rs334348 G > A and TGFBR3 rs1805110G > A exhibited association with decreased POI risk (adjusted odds ratio [AOR] = 0.165; 95% confidence interval [CI] 0.032–0.847; P = 0.031). Also, TGFBR1 rs1590 G > T and rs334348 G > A and TGFBR3 rs1805110 G > A allele combination exhibited association with decreased POI risk (OR = 0.553; 95% CI 0.374–0.816; P = 0.003). Conclusion: This study suggests that polymorphisms in the TGF-β signaling pathway genes can be useful biomarkers for POI diagnosis and treatment. [ABSTRACT FROM AUTHOR]

This paper explores the paradigm shift in nuclear energy generation from large, centralized nuclear power plants towards small modular reactors (SMRs), in response to the evolving economic, safety, and environmental challenges faced by the nuclear industry. For over 70 years, nuclear power has been a cornerstone of electricity generation, offering a low-carbon, reliable, and cost-effective solution. However, the traditional model of large-scale nuclear reactors has encountered significant barriers, including high financial risks, stringent safety concerns, and a lack of adaptability to smaller electrical grids, and changing energy markets. With over 70 types of SMRs currently under development globally, this study reviews several prominent models to assess their general characteristics and potential advantages. Through simple physical and economic models, the paper evaluates the impact of reducing reactor size on efficiency, safety, and cost, highlighting the shared traits and innovations across different SMR designs. The findings indicate that SMRs could address many of the limitations of conventional nuclear power, offering more flexible, scalable, and economically viable options for electricity generation. This paper finally tries to identify key technologies and strategic considerations essential for their successful deployment in a rapidly transforming global energy landscape. [ABSTRACT FROM AUTHOR]

Background: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20–30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery. Patients and Methods: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007–August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model. Results: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44–86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age (≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478–7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335–4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184–4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547–5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%. Conclusions: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether switching to contrast media based on the sharing of N-(2,3-dihydroxypropyl) carbamoyl side chain reduces the recurrence of iodinated contrast media (ICM)-associated adverse drug reactions (ADRs). Materials and methods: This single-center retrospective study included 2133 consecutive patients (mean age ± SD, 56.1 ± 11.4 years; male, 1052 [49.3%]) who had a history of ICM-associated ADRs and underwent contrast-enhanced CT examinations. The per-patient and per-exam-based recurrence ADR rates were compared between cases of switching and non-switching the ICM from ICMs that caused the previous ADRs, and between cases that used ICMs with common and different carbamoyl side chains from ICMs that caused the previous ADRs. Downgrade rates (no recurrence or the occurrence of ADR less severe than index ADRs) were also compared. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis were additionally performed. Results: In per-patient analysis, switching of ICM showed a lower recurrence rate (switching, 10.4% [100/965] vs. non-switching, 28.4% [332/1168]), with the adjusted odds ratio (OR) of 0.27 (95% CI: 0.21, 0.34; p < 0.001). The result was consistent in PSM (OR, 0.29 [95% CI: 0.22, 0.39]; p < 0.001), IPTW (OR, 0.28 [95% CI: 0.22, 0.36]; p < 0.001), and in per-exam analysis (5.5% vs. 13.8%; OR, 0.32 [95% CI: 0.27, 0.37]; p < 0.001). There was lower per-exam recurrence (5.0% [195/3938] vs. 7.8% [79/1017]; OR, 0.63 [95% CI: 0.47, 0.83]; p = 0.001) and higher downgrade rates (95.6% [3764/3938] vs. 93.3% [949/1017]; OR, 1.51 [95% CI: 1.12, 2.03]; p = 0.006) when using different side chain groups. Conclusion: Switching to an ICM with a different carbamoyl side chain reduced the recurrent ADRs and their severity during subsequent examinations. Clinical relevance statement: Switching to an iodinated contrast media with a different carbamoyl side chain reduced the recurrent adverse drug reactions and their severity during subsequent examinations. Key Points: Patients who experience adverse drug reactions from iodinated contrast media (ICM) may need to undergo contrast-enhanced studies again. Switching of ICM away from the ICM that caused the previous adverse drug reactions showed significantly lower recurrence rates. Compared to common side chain groups, there were significant differences in the per-exam recurrence rates and downgrade rates when using ICMs with different side chains. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether a deep learning (DL) controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA)-volumetric interpolated breath-hold examination (VIBE) technique can improve image quality, lesion conspicuity, and lesion detection compared to a standard CAIPIRINHA-VIBE technique in gadoxetic acid–enhanced liver MRI. Methods: This retrospective single-center study included 168 patients who underwent gadoxetic acid–enhanced liver MRI at 3 T using both standard CAIPIRINHA-VIBE and DL CAIPIRINHA-VIBE techniques on pre-contrast and hepatobiliary phase (HBP) images. Additionally, high-resolution (HR) DL CAIPIRINHA-VIBE was obtained with 1-mm slice thickness on the HBP. Three abdominal radiologists independently assessed the image quality and lesion conspicuity of pre-contrast and HBP images. Statistical analyses involved the Wilcoxon signed-rank test for image quality assessment and the generalized estimation equation for lesion conspicuity and detection evaluation. Results: DL and HR-DL CAIPIRINHA-VIBE demonstrated significantly improved overall image quality and reduced artifacts on pre-contrast and HBP images compared to standard CAIPIRINHA-VIBE (p < 0.001), with a shorter acquisition time (DL vs standard, 11 s vs 17 s). However, the former presented a more synthetic appearance (both p < 0.05). HR-DL CAIPIRINHA-VIBE showed superior lesion conspicuity to standard and DL CAIPIRINHA-VIBE on HBP images (p < 0.001). Moreover, HR-DL CAIPIRINHA-VIBE exhibited a significantly higher detection rate of small (< 2 cm) solid focal liver lesions (FLLs) on HBP images compared to standard CAIPIRINHA-VIBE (92.5% vs 87.4%; odds ratio = 1.83; p = 0.036). Conclusion: DL and HR-DL CAIPIRINHA-VIBE achieved superior image quality compared to standard CAIPIRINHA-VIBE. Additionally, HR-DL CAIPIRINHA-VIBE improved the lesion conspicuity and detection of small solid FLLs. DL and HR-DL CAIPIRINHA-VIBE hold the potential clinical utility for gadoxetic acid–enhanced liver MRI. Clinical relevance statement: DL and HR-DL CAIPIRINHA-VIBE hold promise as potential alternatives to standard CAIPIRINHA-VIBE in routine clinical liver MRI, improving the image quality and lesion conspicuity, enhancing the detection of small (< 2 cm) solid focal liver lesions, and reducing the acquisition time. Key Points: • DL and HR-DL CAIPIRINHA-VIBE demonstrated improved overall image quality and reduced artifacts on pre-contrast and HBP images compared to standard CAIPIRINHA-VIBE, in addition to a shorter acquisition time. • DL and HR-DL CAIPIRINHA-VIBE yielded a more synthetic appearance than standard CAIPIRINHA-VIBE. • HR-DL CAIPIRINHA-VIBE showed improved lesion conspicuity than standard CAIPIRINHA-VIBE on HBP images, with a higher detection of small (< 2 cm) solid focal liver lesions. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases remain the leading cause of mortality worldwide, with percutaneous coronary interventions (PCI) using drug-eluting stents (DES) as the standard treatment for coronary artery disease. Despite advancements in DES technology, challenges such as restenosis and stent thrombosis still necessitate further interventions and carry considerable risks, highlighting an urgent need for a novel therapeutic approach with lower restenosis rates and reduced reintervention risks. Drug-eluting balloons (DEBs) coated with anti-proliferative agents offer a novel method of local drug delivery for reducing restenosis by directly administering drugs to the lesion site. However, efficient delivery of drugs within the brief procedural window while minimizing drug loss during maneuvering to the target site remains a challenge. Herein, we developed a pressure-responsive and pH-triggered, paclitaxel (PTX) coated DEB catheter for rapid and high-dose delivery of paclitaxel to the lesion sites, overcoming the limitations of drug dispersion and inefficiencies associated with conventional DEBs. Using the charge reversion of albumin around its isoelectric point, paclitaxel-loaded human serum albumin nanoparticles (PTX-HSA-NPs) and heparin were coated using a layer-by-layer deposition method at pH 4.0. Upon exposure to physiological pH (i.e., 7.4), the coating is rapidly released from the balloon surface. Combined with a protective shellac coating, the DEB achieved controlled release of high-dose paclitaxel to the arterial tissue in vivo (up to 400 µg per gram tissue), exceeding current DEBs in the clinic. These results suggest the pH-responsive, multi-layer coated DEB's potential for superior procedural outcomes, addressing a critical unmet need in PCI. [ABSTRACT FROM AUTHOR]

Tauopathy, including frontotemporal lobar dementia and Alzheimer's disease, describes a class of neurodegenerative diseases characterized by the aberrant accumulation of Tau protein due to defects in proteostasis. Upon generating and characterizing a stable transgenic zebrafish that expresses the human TAUP301L mutant in a neuron-specific manner, we found that accumulating Tau protein was efficiently cleared via an enhanced autophagy activity despite constant Tau mRNA expression; apparent tauopathy-like phenotypes were revealed only when the autophagy was genetically or chemically inhibited. We performed RNA-seq analysis, genetic knockdown, and rescue experiments with clinically relevant point mutations of valosin-containing protein (VCP), and showed that induced expression of VCP, an essential cytosolic chaperone for the protein quality system, was a key factor for Tau degradation via its facilitation of the autophagy flux. This novel function of VCP in Tau clearance was further confirmed in a tauopathy mouse model where VCP overexpression significantly decreased the level of phosphorylated and oligomeric/aggregate Tau and rescued Tau-induced cognitive behavioral phenotypes, which were reversed when the autophagy was blocked. Importantly, VCP expression in the brains of human Alzheimer's disease patients was severely downregulated, consistent with its proposed role in Tau clearance. Taken together, these results suggest that enhancing the expression and activity of VCP in a spatiotemporal manner to facilitate the autophagy pathway is a potential therapeutic approach for treating tauopathy. [ABSTRACT FROM AUTHOR]

This study assessed pretreatment breast MRI coupled with machine learning for predicting early clinical responses to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), focusing on identifying non-responders. A retrospective analysis of 135 TNBC patients (107 responders, 28 non-responders) treated with NAC from January 2015 to October 2022 was conducted. Non-responders were defined according to RECIST guidelines. Data included clinicopathologic factors and clinical MRI findings, with radiomics features from contrast-enhanced T1-weighted images, to train a stacking ensemble of 13 machine learning models. For subgroup analysis, propensity score matching was conducted to adjust for clinical disparities in NAC response. The efficacy of the models was evaluated using the area under the receiver-operating-characteristic curve (AUROC) before and after matching. The model combining clinicopathologic factors and clinical MRI findings achieved an AUROC of 0.752 (95% CI 0.644–0.860) for predicting non-responders, while radiomics-based models showed 0.749 (95% CI 0.614–0.884). An integrated model of radiomics, clinicopathologic factors, and clinical MRI findings reached an AUROC of 0.802 (95% CI 0.699–0.905). After propensity score matching, the hierarchical order of key radiomics features remained consistent. Our study demonstrated the potential of using machine learning models based on pretreatment MRI to non-invasively predict TNBC non-responders to NAC. [ABSTRACT FROM AUTHOR]

It has been reported that a scenario-based cognitive behavioral therapy mobile app including Todac Todac was effective in improving depression in the general public. However, no study has been conducted on whether Todac Todac is effective in dialysis patients. Therefore, this study was intended to determine whether the use of this app was effective in improving depression in dialysis patients. Sixty-five end-stage kidney disease patients receiving dialysis at Soonchunhyang University Cheonan Hospital were randomly assigned to the Todac Todac app program (experimental group) or an E-moods daily mood chart app program (control group) for 3 weeks. The degree of depression was measured before and after using the app.After the end of the 3-week program, a small but significant improvement was observed in the Trait anxiety (p < 0.05) and Beck depression index (p < 0.05) in E-moods group and DAS-K scores (p < 0.05) in Todac Todac group. However, no differences were seen in any parameters between the two groups. In addition, Todac Todac was not statistically more effective than the control intervention in the subgroup analysis. The Todac Todac, a scenario-based cognitive behavioral therapy mobile app, seemed to have a limited effect on improving depression in dialysis patients. Therefore, it is necessary to develop new tools to improve depression in dialysis patients. [ABSTRACT FROM AUTHOR]

Deep neural networks (DNNs) have proven explicit contributions in making autonomous driving cars and related tasks such as semantic segmentation, motion tracking, object detection, sensor fusion, and planning. However, in challenging situations, DNNs are not generalizable because of the inherent domain shift due to the nature of training under the i.i.d. assumption. The goal of semantic segmentation is to preserve information from a given image into multiple meaningful categories for visual understanding. Particularly for semantic segmentation, pixel-wise annotation is extremely costly and not always feasible. Domain generalization for semantic segmentation aims to learn pixel-level semantic labels from multiple source domains and generalize to predict pixel-level semantic labels on multiple unseen target domains. In this survey, for the first time, we present a comprehensive review of DG for semantic segmentation. we present a comprehensive summary of recent works related to domain generalization in semantic segmentation, which establishes the importance of generalizing to new environments of segmentation models. Although domain adaptation has gained more attention in segmentation tasks than domain generalization, it is still worth unveiling new trends that are adopted from domain generalization methods in semantic segmentation. We cover most of the recent and dominant DG methods in the context of semantic segmentation and also provide some other related applications. We conclude this survey by highlighting the future directions in this area. [ABSTRACT FROM AUTHOR]

Selective laser melting (SLM) offers an innovative manufacturing approach compared to traditional methods. It has found diverse applications in various fields, ranging from medical devices to aerospace, using a variety of metals. However, products manufactured with the metal AlSi10Mg using the SLM technique have a significant surface roughness defect. Consequently, products produced through SLM necessitate post-processing. In this study, electro-polishing was conducted on AlSi10Mg specimens manufactured at four different inclinations. Surface roughness measurements and 3D scans were performed at various time intervals to observe changes in roughness. It was observed that an increase in electro-polishing time effectively reduced surface roughness. This research provides data on post-processing for three-dimensional structures manufactured using the SLM technique. [ABSTRACT FROM AUTHOR]

k-Nearest Neighbors (k-NN) is one of the most widely used classification algorithms in real-world machine learning applications such as computer vision, speech recognition, and data mining. Massive high-dimensional datasets, reasonable accuracy of results, and adequate response time are regarded as the most challenging aspects of the k-NN implementation, which are exacerbated by the exponential increase in dataset size and the feature dimension of each data point. In this paper, we leverage the parallelism and digit-level pipelining opportunities offered by FPGA devices and Online arithmetic to address such issues for k-NN classification based on different distance metrics: Manhattan and Euclidean. In these designs, all the necessary operations for measuring distances and sorting are performed on serially arriving data at no or minimal hardware cost. Due to serial computation, the size of the classifier instance and its memory footprint are reduced, leading to more parallel instances for our target devices. Furthermore, we dynamically terminate unnecessary computations upon detection to reduce power consumption, which is possible in more than half of cases on average. The proposed k-NN implementations are the first hardware accelerator designs that effectively use online arithmetic on FPGA. Based on implementation results, our proposed k-NN implementation based on Manhattan distance provides 1.72x to 2.23x Speedup compared to state-of-the-art designs, while these improvements for Euclidean distance are 1.06x to 2.76x. [ABSTRACT FROM AUTHOR]

Background: Microsatellite instability (MSI) status is a strong predictor of response to immunotherapy of colorectal cancer. Radiogenomic approaches promise the ability to gain insight into the underlying tumor biology using non-invasive routine clinical images. This study investigates the association between tumor morphology and the status of MSI versus microsatellite stability (MSS), validating a novel radiomic signature on an external multicenter cohort. Methods: Preoperative computed tomography scans with matched MSI status were retrospectively collected for 243 colorectal cancer patients from three hospitals: Seoul National University Hospital (SNUH); Netherlands Cancer Institute (NKI); and Fondazione IRCCS Istituto Nazionale dei Tumori, Milan Italy (INT). Radiologists delineated primary tumors in each scan, from which radiomic features were extracted. Machine learning models trained on SNUH data to identify MSI tumors underwent external validation using NKI and INT images. Performances were compared in terms of area under the receiving operating curve (AUROC). Results: We identified a radiomic signature comprising seven radiomic features that were predictive of tumors with MSS or MSI (AUROC 0.69, 95% confidence interval [CI] 0.54−0.84, p = 0.018). Integrating radiomic and clinical data into an algorithm improved predictive performance to an AUROC of 0.78 (95% CI 0.60−0.91, p = 0.002) and enhanced the reliability of the predictions. Conclusion: Differences in the radiomic morphological phenotype between tumors MSS or MSI could be detected using radiogenomic approaches. Future research involving large-scale multicenter prospective studies that combine various diagnostic data is necessary to refine and validate more robust, potentially tumor-agnostic MSI radiogenomic models. Relevance statement: Noninvasive radiomic signatures derived from computed tomography scans can predict MSI in colorectal cancer, potentially augmenting traditional biopsy-based methods and enhancing personalized treatment strategies. Key Points: Noninvasive CT-based radiomics predicted MSI in colorectal cancer, enhancing stratification. A seven-feature radiomic signature differentiated tumors with MSI from those with MSS in multicenter cohorts. Integrating radiomic and clinical data improved the algorithm's predictive performance. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the relationship and interdependence of functional properties of the football boot outsole during the shape optimisation process. Sensitivity-based shape optimisation technique was applied to a football boot outsole to modify its thickness to have various functional properties. Three functional properties of the outsole, which are the midfoot and forefoot bending stiffness and torsional stiffness, were investigated. The midfoot and forefoot bending stiffness were measured via a three-point bending test. Torsional stiffness was measured via a bespoken mechanical test. The functional properties were evaluated by finite element models, representing the developed mechanical tests. Through the optimisation tasks, it was explored how much each functional property could be changed individually and also while minimising the influence of the other two functional properties. With the modification of the regions of the outsole to optimise for various individual target functional property values, the changes in the other two functional properties were observed. Lastly, the optimised outsoles from the finite element models were 3D printed and tested to determine the accuracy of the process. Within a permitted thickness limit, modifying the region associated with the torsional stiffness measurement influenced the other two functional properties the most. Especially, the midfoot bending stiffness was influenced more than the forefoot bending stiffness. On the other hand, the areas involved in the midfoot and forefoot bending stiffness measurements were independent of each other. The conclusions drawn in this study are limited to the particular outsole design, single outsole component and mechanical test utilised. [ABSTRACT FROM AUTHOR]

CO2 flux measurements and soil gas samples were collected to determine the origin and distribution characteristics of soil gas discharged at Andeok area, Jeju, South Korea. Additionally, this study aims to discuss agricultural activities that may contribute to increased soil CO2 emissions. CO2 flux was measured at 127 points, while soil gas sampling for gas components and carbon-13 (δ13CCO2) analysis was performed at 56 points. The measured CO2 fluxes in the study area ranged from 0.8 to 83.8 g/m2/d (mean: 14.3 g/m2/d), which was lower than CO2 fluxes observed in areas with geogenic CO2 discharge (e.g., near active volcanoes, faults, and CO2-rich water sources). The soil gas analysis revealed that the CO2 concentration and δ13CCO2 ranged from 491 to 23,722 ppmv (mean: 3,205 ppmv) and from −25.2 to −10.7‰ (mean: −19.4‰), respectively. In the cumulative probability diagram, the threshold values for CO2 flux and soil CO2 concentration were 41.3 g/m2/d and 6,693 ppmv, respectively. Samples exceeding the CO2 flux threshold were affected by urea fertilizer application based on land use nearby, and did not overlay with samples exceeding the soil CO2 threshold, indicating different transport mechanisms. Results from a detailed survey near a soil gas sampling location close to high soil CO2 showed that soil CO2 concentrations increased with depth, especially during summer when atmospheric temperatures increased. Spatially, higher soil CO2 concentrations were observed in areas with accumulated plant debris from tangerine orchards. The δ13CCO2 and relationships among CO2-O2, N2-CO2, and N2/O2-CO2 indicated that all collected samples had a biogenic origin. Although geogenic soil gases were not observed in this study, our findings are useful for future research on Jeju Island, as they provide baseline values for distinguishing geogenic soil gas from those with natural and agricultural origins. Moreover, this result provides insights into agricultural activities such as urea fertilization and plowing and their contribution to soil CO2 increase, and inspires future research on negative soil CO2 flux. [ABSTRACT FROM AUTHOR]

This paper introduces the concept of hesitant bipolar-valued fuzzy graph (HBVFG), which captures the two opposing perspectives, namely the positive and negative opinions. The novelty, importance and implications of this concept are illustrated by some results, examples, and graphical representations. There are, respectively, some theoretical terms of graphs such as partial directed hesitant bipolar-valued fuzzy subgraph (HBVFSG), directed HBVFSG, directed spanning HBVFSG, strong directed HBVFG and complete directed HBVFG which are introduced. The operations, such as Cartesian, direct, lexicographical, and strong products, are also defined between two HBVFGs with examples. The mapping relations, such as homomorphism, isomorphism, weak isomorphism, and co-weak isomorphism, are derived with an example. The applications of directed HBVFGs with algorithms for finding the optimal path in a network and the dominant node and influence of index with the self-persistence degree of a node in a social network are presented. For each problem, an algorithm is developed and its effectiveness is demonstrated by examples. The proposed concept is assessed in terms of theory and practice. The benefits of the proposed solution are highlighted and a clear comparison is made with the existing methods. [ABSTRACT FROM AUTHOR]

Context: Cyclin-dependent kinase 9 (CDK9) plays a significant role in gene regulation and RNA polymerase II transcription under basal and stimulated conditions. The upregulation of transcriptional homeostasis by CDK9 leads to various malignant tumors and therefore acts as a valuable drug target in addressing cancer incidences. Ongoing drug development endeavors targeting CDK9 have yielded numerous clinical candidate molecules currently undergoing investigation as potential CDK9 modulators, though none have yet received Food and Drug Administration (FDA) approval. Methods: In this study, we employ in silico approaches including the molecular docking and molecular dynamics simulations for the virtual screening over the natural compounds library to identify novel promising selective CDK9 inhibitors. The compounds derived from the initial virtual screening were subsequently employed for molecular dynamics simulations and binding free energy calculations to study the compound's stability under virtual physiological conditions. The first-generation CDK inhibitor Flavopiridol was used as a reference to compare with our novel hit compound as a CDK9 antagonist. The 500-ns molecular dynamics simulation and binding free energy calculation showed that two natural compounds showed better binding affinity and interaction mode with CDK9 receptors over the reference Flavopiridol. They also showed reasonable figures in the predicted absorption, distribution, metabolism, excretion, and toxicity (ADMET) calculations as well as in computational cytotoxicity predictions. Therefore, we anticipate that the proposed scaffolds could contribute to developing potential and selective CDK9 inhibitors subjected to further validations. [ABSTRACT FROM AUTHOR]

In this study, a molecular beacon (MB) was designed for colorimetric loop-mediated isothermal amplification (cLAMP). The length of complementary bases on the MB, guanine and cytosine content (GC content), and hybridization sites of complementary bases were investigated as key factors affecting the design of the MB. We designed MBs consisting of 10, 15, and 20 complementary bases located at both ends of the HRPzyme. In the case of the long dumbbell DNA structure amplified from the hlyA gene of Listeria monocytogenes, possessing a flat region (F1c-B1) of 61 base pairs (bp), an MB was designed to intercalate into the flat region between the F1c and B1 regions of the LAMP amplicons. In the case of the short dumbbell DNA structure amplified from the bcfD gene of Salmonella species possessing a flat region (F1c-B1) length of 6 bp, another MB was designed to intercalate into the LoopF or LoopB regions of the LAMP amplicons. The results revealed that the hybridization site of the MB on the LAMP amplicons was not crucial in designing the MB, but the GC content was an important factor. The highest hybridization efficiencies for LAMP amplicons were obtained from hlyA gene-specific and bcfD gene-specific MBs containing 20- and 15-base complementary sequences, respectively, which exhibited the highest GC content. Therefore, designing MBs with a high GC content is an effective solution to overcome the low hybridization efficiency of cLAMP assays. The results obtained can be used as primary data for designing MBs to improve cLAMP accessibility. [ABSTRACT FROM AUTHOR]

With the increase in the dependency on digital devices, the incidence of myopia, a precursor of various ocular diseases, has risen significantly. Because myopia and eyeball volume are related, myopia progression can be monitored through eyeball volume estimation. However, existing methods are limited because the eyeball shape is disregarded during estimation. We propose an automated eyeball volume estimation method from computed tomography images that incorporates prior knowledge of the actual eyeball shape. This study involves data preprocessing, image segmentation, and volume estimation steps, which include the truncated cone formula and integral equation. We obtained eyeball image masks using U-Net, HFCN, DeepLab v3 +, SegNet, and HardNet-MSEG. Data from 200 subjects were used for volume estimation, and manually extracted eyeball volumes were used for validation. U-Net outperformed among the segmentation models, and the proposed volume estimation method outperformed comparative methods on all evaluation metrics, with a correlation coefficient of 0.819, mean absolute error of 0.640, and mean squared error of 0.554. The proposed method surpasses existing methods, provides an accurate eyeball volume estimation for monitoring the progression of myopia, and could potentially aid in the diagnosis of ocular diseases. It could be extended to volume estimation of other ocular structures. [ABSTRACT FROM AUTHOR]

Objectives: To identify MRI features for differentiating type 2 from type 1 intraductal papillary neoplasms of bile duct (IPNB) and assessing malignant potential of IPNB. Methods: This retrospective study included 60 patients with surgically proven IPNB who had undergone preoperative MRI between January 2007 and December 2020. All surgical specimens were reviewed retrospectively to classify types 1 and 2 IPNBs and assess tumor grade. Significant MRI features for differentiating type 2 (n = 40) from type 1 IPNB (n = 20); and for IPNB with an associated invasive carcinoma (n = 43) from intraepithelial neoplasia (n = 17) were determined using logistic regression analysis. Results: An associated invasive carcinoma was more frequently found in type 2 than in type 1 IPNB (85.0% [34/40] vs. 45.0% [9/20], p = 0.003). At univariable analysis, MRI features including extrahepatic location, no dilatation of tumor-bearing segment of bile duct, isolated upstream bile duct dilatation, and single lesion were associated with type 2 IPNB (all p ≤ 0.012). At multivariable analysis, significant MRI findings for differentiating type 2 from type 1 IPNB were extrahepatic location and no dilatation of tumor-bearing segment of bile duct (odds ratio [OR], 7.24 and 46.40, respectively). At univariable and multivariable analysis, tumor size ≥ 2.5 cm (OR, 8.45), bile duct wall thickening (OR, 4.82), and irregular polypoid or nodular tumor shape (OR, 6.44) were significant MRI features for differentiating IPNB with an associated invasive carcinoma from IPNB with intraepithelial neoplasia. Conclusion: MRI with MR cholangiopancreatography may be helpful in differentiating type 2 IPNB from type 1 IPNB and assessing malignant potential of IPNB. Clinical relevance statement: Preoperative MRI with MR cholangiopancreatography may be helpful in differentiating type 2 intraductal papillary neoplasms of bile duct (IPNB) from type 1 IPNB and assessing malignant potential of IPNB. Key Points: • In terms of tumor grade, the incidence of invasive carcinoma was significantly higher in type 2 intraductal papillary neoplasm of the bile duct (IPNB) than in type 1 IPNB. • At MRI, extrahepatic location and no dilatation of tumor-bearing segment are significant features for differentiating type 2 IPNBs from type 1 IPNBs. • At MRI, large tumor size, bile duct wall thickening, and irregular polypoid or nodular tumor shape are significant features for differentiating IPNB with an associated invasive carcinoma from IPNB with intraepithelial neoplasia. [ABSTRACT FROM AUTHOR]

Adenoviral vectors are crucial for gene therapy and vaccine development, offering a platform for gene delivery into host cells. Since the discovery of adenoviruses, first-generation vectors with limited capacity have evolved to third-generation vectors flacking viral coding sequences, balancing safety and gene-carrying capacity. The applications of adenoviral vectors for gene therapy and anti-viral treatments have expanded through the use of in vitro ligation and homologous recombination, along with gene editing advancements such as CRISPR-Cas9. Current research aims to maintain the efficacy and safety of adenoviral vectors by addressing challenges such as pre-existing immunity against adenoviral vectors and developing new adenoviral vectors from rare adenovirus types and non-human species. In summary, adenoviral vectors have great potential in gene therapy and vaccine development. Through continuous research and technological advancements, these vectors are expected to lead to the development of safer and more effective treatments. [ABSTRACT FROM AUTHOR]

The emergence of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a pandemic, prompting rapid vaccine development. Although vaccines are effective, the occurrence of rare adverse events following vaccination highlights the necessity of determining whether the benefits outweigh the risks posed by the infection itself. The recombinant Vesicular Stomatitis Virus (rVSV) platform is a promising vector for vaccines against emerging viruses. However, limited studies have evaluated the genotoxicity and safety pharmacology of this viral vector vaccine, which is crucial to ensure the safety of vaccines developed using this platform. Hence, the present study aimed to assess the genotoxicity and safety pharmacology of the rVSVInd(GML)-mspSGtc COVID-19 vaccine using micronucleus and comet assays, as well as neurobehavioral, body temperature, respiratory, and cardiovascular assessments in Sprague–Dawley rats and beagle dogs. The intramuscular administration of rVSVInd(GML)-mspSGtc at doses up to 1.5 × 109 PFU/animal did not increase the number of bone marrow micronucleated polychromatic erythrocytes or cause liver DNA damage. Additionally, it had no significant impact on neurobehavioral functions in rats and showed marginal temporary changes in body temperature, respiratory rate, heart rate, and electrocardiogram parameters in rats and dogs, all of which resolved within 24 h. Overall, following genotoxicity and pharmacological safety assessments, rVSVInd(GML)-mspSGtc displayed no notable systemic adverse effects in rats and dogs, suggesting its potential as a vaccine candidate for human clinical trials. [ABSTRACT FROM AUTHOR]

Background: During sentinel node navigation surgery in patients with gastric cancer, intraoperative pathologic examination of sentinel nodes is crucial in determining the extent of surgery. In this study, we evaluated the feasibility and accuracy of intraoperative pathologic protocols using data from a prospective, multicenter, randomized trial. Methods: A retrospective analysis was conducted using data from the SEntinel Node ORIented Tailored Approach trials from 2013 to 2016. All sentinel lymph nodes were evaluated during surgery with hematoxylin–eosin (HE) staining using a representative section at the largest plane for lymph nodes. For permanent histologic evaluation, sentinel basin nodes were stained with HE and cytokeratin immunohistochemistry in formalin-fixed, paraffin-embedded (FFPE) sections and examined with HE for three deeper-step sections at 200-μm intervals. The failure rate of identification by frozen section and the metastasis rate in non-sentinel basins were investigated. Results: Of the 237 patients who underwent sentinel node basin dissection, 30 had lymph node metastases on permanent pathology. Thirteen patients had macrometastasis confirmed in frozen sections as well as FFPE sections (failure rate: 0%). Patients with negative sentinel nodes in frozen sections but micrometastasis in FFPE sections had no lymph node recurrence during the follow-up period (0%, 0/6). However, in cases with tumor-positive nodes in frozen sections, metastases in non-sentinel basins were detected in the paraffin blocks (8.3%, 2/24). Conclusions: The single-section HE staining method is sufficient for detecting macrometastasis via intraoperative pathological examination. If a negative frozen-section result is confirmed, sentinel basin dissection can be performed safely. Otherwise, standard surgery is required. [ABSTRACT FROM AUTHOR]

Background: Postendoscopic submucosal dissection electrocoagulation syndrome (PEECS) is commonly observed after performing endoscopic submucosal dissection (ESD) for esophageal neoplasia. However, data on the incidence and risk factors for PEECS in the esophagus are lacking due to an unclear definition of PEECS and varied clinical settings. Therefore, we aimed to determine the risk factors for PEECS in patients undergoing ESD for esophageal neoplasia. Methods: We retrospectively reviewed data of relevant clinical and endoscopy-specific parameters from 202 consecutive patients with esophageal neoplasias (139 carcinomas and 63 dysplasias) who underwent ESD under general anesthesia. Esophageal PEECS was defined by satisfying at least two of the following criteria: fever ≥ 37.8 °C, leukocytosis ≥ 10,800/mm3, and localized chest pain ≥ 5/10 points as assessed on a numeric rating scale within 24 h after ESD. Significant factors associated with PEECS were determined by regression analysis. Results: PEECS was recorded in 98 of 202 (48.5%) patients. Patients with PEECS exhibited a larger tumor size (25.0 vs. 17.0 mm, P = 0.002), longer procedure (40.0 vs. 29.5 min, P = 0.021) and hemostasis times (5.0 vs. 3.5 min, P = 0.004), required greater submucosal injection volume (60.0 mL vs. 50.0 mL, P = 0.030), and had a lower rate of local steroid injection (4.1% vs. 12.5%, P = 0.029) than those without PEECS. Multivariate regression analysis revealed tumor size ≥ 17 mm (P = 0.047), procedure time ≥ 33 min (P = 0.027), and hemostasis time ≥ 5 min (P = 0.007) as risk factors for PEECS. In addition, local steroid injection was a significant negatively associated factor (P = 0.001). Conclusions: Patients with a large tumor, prolonged procedure and hemostasis times are at a high risk of PEECS occurrence. Further, local steroid injection is a negatively associated factor. [ABSTRACT FROM AUTHOR]

The objective of this investigation is to ascertain the determinants associated with the amelioration of symptoms in female patients suffering from overactive bladder (OAB) following treatment with 0.2 mg of imidafenacin. The study included 66 female OAB patients who had been prescribed a daily dose of 0.2 mg imidafenacin for a minimum of 3 months, spanning from March 2018 to June 2020. Various clinical parameters including age, coexistence of additional voiding symptoms, prior history of urological surgeries, and responses to the Overactive Bladder Symptom Score questionnaire (OABSS), both pre- and post-initiation of imidafenacin therapy, were evaluated. The mean total OABSS scores recorded before and 3 months subsequent to imidafenacin therapy were 8.36 ± 3.65 and 5.15 ± 3.22, respectively. Following the 3-month course of imidafenacin treatment, there was a statistically significant improvement in both the total OABSS score and the severity of OAB symptoms (p < 0.001 for both). Prior to treatment initiation, Group B (n = 38) exhibited significantly higher total OABSS scores and subscores compared to Group A (n = 28) (p < 0.05). Multivariable analysis identified the OABSS subscores for items 1 and 3 prior to treatment as significant predictors for the improvement of OAB severity subsequent to imidafenacin therapy (p = 0.046, OR 3.10, 95% CI 1.019–9.440 and p < 0.001, OR 2.77, 95% CI 1.671–4.587, respectively). Consequently, imidafenacin emerges as an efficacious therapeutic agent for alleviating OAB severity in female patients, with the OABSS subscores for items 1 and 3 prior to treatment initiation holding potential utility in predicting the efficacy of imidafenacin in managing OAB. [ABSTRACT FROM AUTHOR]

The objective of this study is to examine the determinants influencing the efficacy of intravesical administration of botulinum toxin A (BoNT-A) in patients suffering from overactive bladder (OAB). The study included 32 females diagnosed with OAB, with or without urge urinary incontinence. All participants underwent BoNT-A injections (100 units) at the posterior bladder wall (20 points) from our institution between March 2017 and June 2020. Clinical data was gathered, and the severity of OAB was evaluated both before and four weeks following the procedure utilizing the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence (ICIG-UI) and the Overactive Bladder Symptom Score (OABSS). The study also looked into the status of medication for OAB four weeks after the procedure. Total mean ICIQ-UI and OABSS were significantly improved four weeks after BoNT-A injection (14.00 ± 3.46 to 7.00 ± 6.82, p < 0.001 and 11.40 ± 5.01 to 6.40 ± 1.25, p = 0.009, respectively). Younger age, longer OAB duration, and ongoing OAB medication were the factors that significantly improved the effectiveness of BoNT-A injection. [ABSTRACT FROM AUTHOR]

Hemophilia is a genetic disorder that is caused by mutations in coagulation factor VIII (hemophilia A) or IX (hemophilia B) genes resulting in blood clotting disorders. Despite advances in therapies, such as recombinant proteins and products with extended half-lives, the treatment of hemophilia still faces two major limitations: the short duration of therapeutic effect and production of neutralizing antibodies against clotting factors (inhibitor). To overcome these limitations, new hemophilia treatment strategies have been established such as gene therapy, bispecific antibody, and rebalancing therapy. Although these strategies have shown promising results, it is difficult to achieve a permanent therapeutic effect. Advances in the clustered regularly interspaced short palindromic repeat (CRISPR) technology have allowed sustainable treatment by correcting mutated genes. Since genome editing generates irreversible changes in host genome, safety must be ensured by delivering target organs. Therefore, the delivery tool of the CRISPR system is crucial for safe, accurate, and efficient genome editing. Recently, non-viral vector lipid nanoparticles (LNPs) have emerged as safer tools for delivering CRISPR systems than other viral vectors. Several previous hemophilia pre-clinical studies using LNP-CRISPR showed that sufficient and sustainable therapeutic effects, which means that LNP-CRISPR-mediated genome-editing therapy can be a valid option for the treatment of hemophilia. In this paper, we summarize the latest advancements in the successful treatment of hemophilia and the potential of CRISPR-mediated genome-editing therapy using LNPs. [ABSTRACT FROM AUTHOR]

Adenovirus (Ad) is a ubiquitous pathogen capable of infecting a wide range of animals and humans. Human Adenovirus (HAdV) can cause severe infection, particularly in individuals with compromised immune systems. To date, over 110 types of HAdV have been classified into seven species from A to G, with the majority belonging to the human adenovirus species D (HAdV-D). In the HAdV-D, the most significant factor for the creation of new adenovirus types is homologous recombination between viral genes involved in determining the virus tropism or evading immune system of host cells. The E4 gene, consisting of seven Open Reading Frames (ORFs), plays a role in both the regulation of host cell metabolism and the replication of viral genes. Despite long-term studies, the function of each ORF remains unclear. Based on our updated information, ORF2, ORF3, and ORF4 have been identified as regions with relatively high mutations compared to other ORFs in the E4 gene, through the use of in silico comparative analysis. Additionally, we managed to visualize high mutation sections, previously undetectable at the DNA level, through a powerful amino acid sequence analysis tool known as proteotyping. Our research has revealed the involvement of the E4 gene in the evolution of human adenovirus, and has established accurate sequence information of the E4 gene, laying the groundwork for further research. [ABSTRACT FROM AUTHOR]

Human adenoviruses (HAdVs) can infect various epithelial mucosal cells, ultimately causing different symptoms in infected organ systems. With more than 110 types classified into seven species (A–G), HAdV-D species possess the highest number of viruses and are the fastest proliferating. The emergence of new adenovirus types and increased diversity are driven by homologous recombination (HR) between viral genes, primarily in structural elements such as the penton base, hexon and fiber proteins, and the E1 and E3 regions. A comprehensive analysis of the HAdV genome provides valuable insights into the evolution of human adenoviruses and identifies genes that display high variation across the entire genome to determine recombination patterns. Hypervariable regions within genetic sequences correlate with functional characteristics, thus allowing for adaptation to new environments and hosts. Proteotyping of newly emerging and already established adenoviruses allows for prediction of the characteristics of novel viruses. HAdV-D species evolved in a direction that increased diversity through gene recombination. Bioinformatics analysis across the genome, particularly in highly variable regions, allows for the verification or re-evaluation of recombination patterns in both newly introduced and pre-existing viruses, ultimately aiding in tracing various biological traits such as virus tropism and pathogenesis. Our research does not only assist in predicting the emergence of new adenoviruses but also offers critical guidance in regard to identifying potential regulatory factors of homologous recombination hotspots. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the association between social support during the re-entry period and long-term health-related quality of life (HRQoL) in breast cancer survivors using a longitudinal cohort study. Methods: This is a prospective cohort study with 275 breast cancer survivors who reported HRQoL at 5 and 10 years after diagnosis. Social support for the re-entry period was measured 3 years after diagnosis using the Medical Outcome Study Social Support Survey (MOS-SSS). HRQoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and Breast Cancer-Specific Module (BR-23). Multivariable linear regression analysis was performed to evaluate HRQoL at 5 and 10 years after diagnosis by level of social support during the re-entry period. Results: The mean (SD) of social support during re-entry period was 68.5. The low social support (LSS, score < 55) group during the re-entry period had a significantly lower HRQoL (mean difference = − 12.93) compared to moderate or high social support (MHSS, score ≥ 55) group. 5 and 10 years after diagnosis, the LSS group continued to demonstrate lower HRQoL (5 years: − 7.17; 10 years: − 7.85) compared to the MHSS group. The LSS group were more likely to have lower role and social function scores, and higher fatigue, pain, and financial problems compared to the MHSS group at 10 years after diagnosis. Conclusions: Breast cancer survivors who received lower social support during the re-entry period were more likely to experience poorer HRQoL in the long term than those who did not. [ABSTRACT FROM AUTHOR]

Background: In recognition of the distinct clinical challenges and research gaps in young breast cancer (YBC) patients, we established the Comprehensive Young Age Breast Cancer (CHARM) registry to collect prospective data. Methods: This prospective cohort included patients who were newly diagnosed with histologically confirmed breast cancer without prior treatment at the Samsung Medical Center (SMC) in April 2013. We included patients who were either 40 years old or younger at the time of diagnosis, pregnant at breast cancer diagnosis or diagnosed with breast cancer within 1 year of delivery. All data were collected using Medidata's Rave Electronic Data. Clinical data were obtained from electronic medical records. Two experienced pathologists reviewed the pathologic data. Bone mineral densitometry tests have been conducted annually. To obtain multi-omics data, tumor tissues and blood samples were prospectively collected from consenting patients in the registry during surgery. The fertility-related factor also collected collaborated with the Department of Obstetrics and Gynecology. Anti-Müllerian hormone, estradiol, follicle-stimulating hormone, and luteinizing hormone levels were measured using an additional blood sample from baseline to last follow-up. Patient-reported outcomes were assessed using mobile questionnaires. Results: A total of 1868 participants were included in the SMC YBC study. The average (standard deviation) age was 35.57 (3.79) and 99.8% of the participants were premenopausal. Among them, 1062 participants completed the PRO questionnaires. Conclusions: The SMC YBC cohort serves as a comprehensive registry for YBC to optimize care and improve knowledge regarding the management of YBC. [ABSTRACT FROM AUTHOR]

Background: As breast augmentation has become more popular, an increasing number of women with augmented breasts require treatment for breast cancer. This study aimed to assess the outcomes of postoperative whole breast radiation therapy (WB-RT) in Asian patients with breast cancer who underwent prior cosmetic breast implantation. Methods: We retrospectively reviewed the medical records of 61 patients with breast cancer who had prior cosmetic breast implants (prior-CBI) and underwent breast-conserving surgery (BCS) and WB-RT between 2015 and 2020. The median implant volume was 238.8 cc, with a median interval of 84.7 months between the prior-CBI and BCS. WB-RT was administered with either conventional fractionation (CF-RT) at 50 Gy in 25 fractions (N = 36) or hypofractionation (HF-RT) at 42.6 Gy in 16 fractions (N = 25). The incidences of implant-related complications (IRC) and their contributing factors were analyzed. Results: After a median follow-up of 43.5 months, the 3-year cumulative incidences of IRC and implant loss were 17.2% and 4.9%, respectively. Among the four (6.6%) patients who opted for implant removal after RT, three were potentially related to RT-related capsular contracture. There was no difference in the 3-year cumulative IRC rates following CF-RT and HF-RT (12.2% and 26.7%, respectively; p = 0.120). The risk factors for IRC included a larger implant size (> 260 cc) and a higher ratio of breast tissue to implant volume. Conclusions: This study demonstrated a favorable safety profile of WB-RT for treatment of breast cancer in Asian women with prior-CBI. The integration of HF-RT following BCS was thought to be a feasible approach. [ABSTRACT FROM AUTHOR]

Introduction: Erythrocytosis is attributed to various clinical and molecular factors. Many cases of JAK2-unmutated erythrocytosis remain undiagnosed. We investigated the characteristics and causes of JAK2-unmutated erythrocytosis. Methods: We assessed the clinical and laboratory results of patients with erythrocytosis without JAK2 mutations and performed targeted next-generation sequencing (NGS) panels for somatic and germline mutations. Results: In total, 117 patients with JAK2-unmutated erythrocytosis were included. The median hemoglobin and hematocrit levels were 17.9 g/dL and 53.4%, respectively. Erythropoietin levels were not below the reference range. Thrombotic events were reported in 17 patients (14.5%). Among JAK2-unmutated patients, 44 had undergone targeted panel sequencing consisting of myeloid neoplasm-related genes, and 16 had one or more reportable variants in ASXL1 (5/44), TET2, CALR, FLT3, and SH2B3 (2/44). Additional testing for germline causes revealed eight variants in seven genes in eight patients, including NF1, BPGM, EPAS1, PIEZO1, RHAG, SH2B3, and VHL genes. One NF1 pathogenic, one BPGM likely pathogenic, and six variants of undetermined significance were detected. Conclusion: Somatic and germline mutations were identified in 36.4% and 33.3 % of the JAK2-unmutated group; most variants had unknown clinical significance. Not all genetic causes have been identified; comprehensive diagnostic approaches are crucial for identifying the cause of erythrocytosis. [ABSTRACT FROM AUTHOR]

Background: Most gastric leiomyomas are asymptomatic and benign subepithelial tumors (SETs); however, some may increase in size or become symptomatic. Understanding their natural history is therefore important to their management. We investigated the natural history of histologically proven gastric leiomyomas. Methods: We retrospectively reviewed histologically proven gastric leiomyoma cases at a tertiary center. The baseline characteristics of these cases were analyzed, and those with a follow-up period of at least 12 months without immediate resection were evaluated. The primary outcome was the frequency of size increase of more than 25% during the follow-up period, and the secondary outcome was the histopathologic results in cases that underwent resection. Results: Among the 231 patients with histologically proven gastric leiomyomas, the most frequent location was the cardia (77.1%), and the median size was 3 cm (IQR 2–4 cm). Eighty-four cases were followed up over a median period of 50.8 months (IQR 27.2–91.3 months). During the follow-up period, tumor size increased in two cases (2.4%). Surgical results showed that one case was leiomyoma, and the other was leiomyosarcoma. Among the remaining cases without change in size, 15 underwent surgical resection (n = 10) or endoscopic resection (n = 5), and all cases were confirmed as leiomyoma. Conclusions: Most gastric leiomyomas are benign SETs, and an increase in size is not frequent, even in large-sized cases. Close monitoring with routine follow-up without resection may be sufficient in cases of histologically proven gastric leiomyoma. However, in cases of ulceration or size increase, resection may be beneficial. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) patients are more likely to have BRCA1/2 mutations, with a prevalence rate of about 10–20%. Although several studies have analyzed the oncologic outcomes between BRCA1/2 carriers and non-carriers, the impact on breast cancer patients is still unclear. A retrospective review was performed to determine the long-term outcomes of TNBC patients, focusing on the impact of BRCA1/2 mutations. A total of 953 TNBC patients who underwent primary breast cancer surgery from June 2008 to January 2016 were included. We examined long-term outcomes, including contralateral breast cancer (CBC) incidence, recurrence patterns, and survival rates over a median follow-up of 80.9 months (range 3–152 months). 122 patients (12.8%) had BRCA1/2 mutations. BRCA1/2 mutation carriers were significantly younger at diagnosis and more likely to have a family history of breast/ovarian cancer. CBC incidence at 60, 120, and 150 months was significantly higher in BRCA1/2 mutation carriers compared to non-carriers (P = 0.0250, 0.0063, and 0.0184, respectively). However, there were no significant differences in disease-free survival, overall survival, breast cancer-specific survival, or distant-metastasis-free survival between the two groups. BRCA1/2 mutation status was a significant risk factor for CBC (HR = 6.242, P < 0.0001). Interestingly, among 29 patients with CBC recurrence, 24 patients (82.8%) had recurring TNBC subtype and among the CBC recurrence patients, 19 patients (65.5%) resumed chemotherapy. In the TNBC subtype, appropriate genetic testing and counseling are pivotal for surgical decisions like risk-reducing mastectomy (RRM). Furthermore, long-term surveillance is warranted, especially in BRCA1/2 carriers who did not receive RRM. [ABSTRACT FROM AUTHOR]

This retrospective study evaluated the safety and efficacy of fluoroscopy-guided urethral catheterization in patients who failed blind or cystoscopy-assisted urethral catheterization. We utilized our institutional database between January 2011 and March 2023, and patients with failed blind or cystoscopy-assisted urethral catheterization and subsequent fluoroscopy-guided urethral catheterization were included. A 5-Fr catheter was inserted into the urethral orifice, and the retrograde urethrography (RGU) was acquired. Subsequently, the operator attempted to pass a hydrophilic guidewire to the urethra. If the guidewire and guiding catheter could be successfully passed into the bladder, but the urethral catheter failed pass due to urethral stricture, the operator determined either attempted again with a reduced catheter diameter or performed balloon dilation according to their preference. Finally, an appropriately sized urethral catheter was selected, and an endhole was created using an 18-gauge needle. The catheter was then inserted over the wire to position the tip in the bladder lumen and ballooned to secure it. We reviewed patients’ medical histories, the presence of hematuria, and RGU to determine urethral abnormalities. Procedure-related data were assessed. Study enrolled a total of 179 fluoroscopy-guided urethral catheterizations from 149 patients (all males; mean age, 73.3 ± 13.3 years). A total of 225 urethral strictures were confirmed in 141 patients, while eight patients had no strictures. Urethral rupture was confirmed in 62 patients, and hematuria occurred in 34 patients after blind or cystoscopy-assisted urethral catheterization failed. Technical and clinical success rates were 100%, and procedure-related complications were observed in four patients (2.2%). The mean time from request to urethral catheter insertion was 129.7 ± 127.8 min. The mean total fluoroscopy time was 3.5 ± 2.5 min and the mean total DAP was 25.4 ± 25.1 Gy cm2. Balloon dilation was performed in 77 patients. Total procedure time was 9.2 ± 7.6 min, and the mean procedure time without balloon dilation was 7.1 ± 5.7 min. Fluoroscopy-guided urethral catheterization is a safe and efficient alternative in patients where blind or cystoscopy-assisted urethral catheterization has failed or when cystoscopy-urethral catheterization cannot be performed. [ABSTRACT FROM AUTHOR]

This study explains the development of a manufacturing process that is machinable for a ceramic product. The initial process involves manufacturing a ceramic slurry, which is a mixture of high-weight percentage ceramic powders, and a polymeric binder. The ceramic slurry is then pressed to shape a solid body knwon as the green part, which can be structured using conventional machining tools. The structured green part undergoes a debinding process, the resulting body is referred to as the brown part. Finally, sintering is performed to merge the peripheral ceramic powders, and the white part is obtained. The white part exhibited approximately 18 % isotropic shrinkage in dimension and 9.4 % weight reduction compared with the initial green part. The durability of each part is determined via impact-resistant and microindentation tests. The fracture-resistant energy of the white part is determined as 0.673 J, which is an increase of approximately 500 % compared with the values of other parts. Furthermore, the elastic modulus of the white part is determined to be 14.7 GPa, representing an increase of approximately 270 %. In conclusion, we employed an innovative manufacturing process for ceramic products to address the challenges in conventional methods. [ABSTRACT FROM AUTHOR]

All-solid-state batteries using Si as the anode have shown promising performance without continual solid-electrolyte interface (SEI) growth. However, the first cycle irreversible capacity loss yields low initial Coulombic efficiency (ICE) of Si, limiting the energy density. To address this, we adopt a prelithiation strategy to increase ICE and conductivity of all-solid-state Si cells. A significant increase in ICE is observed for Li1Si anode paired with a lithium cobalt oxide (LCO) cathode. Additionally, a comparison with lithium nickel manganese cobalt oxide (NCM) reveals that performance improvements with Si prelithiation is only applicable for full cells dominated by high anode irreversibility. With this prelithiation strategy, 15% improvement in capacity retention is achieved after 1000 cycles compared to a pure Si. With Li1Si, a high areal capacity of up to 10 mAh cm–2 is attained using a dry-processed LCO cathode film, suggesting that the prelithiation method may be suitable for high-loading next-generation all-solid-state batteries. All-solid-state batteries with silicon anodes have high capacities but low initial coulombic efficiencies (ICEs) because of first cycle irreversible capacity loss. Here, the authors report a prelithiation strategy to improve ICEs and reversibility. [ABSTRACT FROM AUTHOR]

Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines. [ABSTRACT FROM AUTHOR]

Pak-choi (Brassica rapa ssp. chinensis) is a popular vegetative crop in southern China, East Asia, and Southeast Asia. Owing to the threat of climate change, rapid breeding strategies for vegetable cultivars that are tolerant to abiotic and biotic stresses are required. Thus, the rapid fixation of useful agronomic traits using doubled haploid technology is urgent. The haploid-inducer gene is key to doubled haploidization. Two known CENH3 and pPLAIIγ genes, in which altered or partially deleted forms lead to haploid induction, were selected, and direct editing of Pak-choi CENH3 and pPLAIIγ genes (BcCENH3 and BcpPLAIIγ) was conducted using an Agrobacterium-mediated CRISPR/Cas9 system. First, BcCENH3 and BcpPLAIIγ genes were characterized by analyzing the spatial expression patterns and subcellular localization. The CENH3 expression levels in carpels and pPLAIIγ in various parts of Pak-choi flowers were higher than those of other parts. BcCENH3 and BcpPLAIIγ proteins targeted in the nucleus and plasma membrane, respectively. Whole plants were successfully regenerated from the shoot apical meristem (SAM) regions of Pak-choi seedlings using the optimized procedure and culture conditions. The regeneration results of SAM explants after Agrobacterium-mediated transformation of constructs expressing CRISPR/Cas9 and BcCENH3 or BcpPLAIIγ sgRNAs confirmed four independent BcCENH3-targeted transgenic lines with 2.1%, 1.8%, 1.8%, and 1.7% INDEL frequencies, and three independent BcpPLAIIγ-targeted transgenic lines with 24.5%, 33.7%, and 33.0% INDEL frequencies. Thus, our results suggested the possibility of developing transgenic Pak-choi lines by applying the CRISPR/Cas9 genome editing technology to BcCENH3 and BcpPLAIIγ as two haploid-inducer genes. [ABSTRACT FROM AUTHOR]

The pathogenic free-living amoebae, Naegleria fowleri and Acanthamoeba polyphaga, are found in freshwater, soil, and unchlorinated or minimally chlorinated swimming pools. N. fowleri and A. polyphaga are becoming problematic as water leisure activities and drinking water are sources of infection. Chlorine dioxide (ClO2) gas is a potent disinfectant that is relatively harmless to humans at the concentration used for disinfection. In this study, we examined the amoebicidal effects of ClO2 gas on N. fowleri and A. polyphaga. These amoebae were exposed to ClO2 gas from a ready-to-use product (0.36 ppmv/h) for 12, 24, 36, and 48 h. Microscopic examination showed that the viability of N. fowleri and A. polyphaga was effectively inhibited by treatment with ClO2 gas in a time-dependent manner. The growth of N. fowleri and A. polyphaga exposed to ClO2 gas for 36 h was completely inhibited. In both cases, the mRNA levels of their respective actin genes were significantly reduced following treatment with ClO2 gas. ClO2 gas has an amoebicidal effect on N. fowleri and A. polyphaga. Therefore, ClO2 gas has been proposed as an effective agent for the prevention and control of pathogenic free-living amoeba contamination. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has evoked a worldwide pandemic. As the emergence of variants has hampered the neutralization capacity of currently available vaccines, developing effective antiviral therapeutics against SARS-CoV-2 and its variants becomes a significant challenge. The main protease (Mpro) of SARS-CoV-2 has received increased attention as an attractive pharmaceutical target because of its pivotal role in viral replication and proliferation. Here, we generated a de novo Mpro-inhibitor screening platform to evaluate the efficacies of Mpro inhibitors based on Mpro cleavage site-embedded amyloid peptide (MCAP)-coated gold nanoparticles (MCAP-AuNPs). We fabricated MCAPs comprising an amyloid-forming sequence and Mpro-cleavage sequence, mimicking in vivo viral replication process mediated by Mpro. By measuring the proteolytic activity of Mpro and the inhibitory efficacies of various drugs, we confirmed that the MCAP-AuNP-based platform was suitable for rapid screening potential of Mpro inhibitors. These results demonstrated that our MCAP-AuNP-based platform has great potential for discovering Mpro inhibitors and may accelerate the development of therapeutics against COVID-19.The main protease (Mpro) plays a crucial role in the replication of SARS-CoV-2, thereby making it an attractive target for COVID-19 treatment. Here, the authors develop a colorimetric screening platform for discovering Mpro inhibitors using engineered amyloid peptide-based nanocomplexes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of a vendor-specific deep learning reconstruction algorithm (DLRA) in enhancing image quality and focal lesion detection using three-dimensional T1-weighted gradient-echo images in gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) in patients at a high risk of hepatocellular carcinoma. Materials and methods: In this retrospective analysis, 83 high-risk patients with hepatocellular carcinoma underwent gadoxetic acid-enhanced liver MRI using a 3-T scanner. Triple arterial phase, high-resolution portal venous phase, and high-resolution hepatobiliary phase images were reconstructed using conventional reconstruction techniques and DLRA (AIRTM Recon DL; GE Healthcare) for subsequent comparison. Image quality and solid focal lesion detection were assessed by three abdominal radiologists and compared between conventional and DL methods. Focal liver lesion detection was evaluated using figures of merit (FOMs) from a jackknife alternative free-response receiver operating characteristic analysis on a per-lesion basis. Results: DLRA-reconstructed images exhibited significantly improved overall image quality, image contrast, lesion conspicuity, vessel conspicuity, and liver edge sharpness and reduced subjective image noise, ringing artifacts, and motion artifacts compared to conventionally reconstructed images (all P < 0.05). Although there was no significant difference in the FOMs of non-cystic focal liver lesions between the conventional and DL methods, DLRA-reconstructed images showed notably higher pooled sensitivity than conventionally reconstructed images (P < 0.05) in all phases and higher detection rates for viable post-treatment HCCs in the arterial and hepatobiliary phases (all P < 0.05). Conclusions: Implementing DLRA can enhance the image quality in 3D T1-weighted gradient-echo sequences of gadoxetic acid-enhanced liver MRI examinations, leading to improved detection of viable post-treatment HCCs. [ABSTRACT FROM AUTHOR]

Background: Cancer-associated fibroblasts (CAFs) play a crucial role in tumor microenvironment regulation and cancer progression. This study assessed the significance and predictive potential of CAFs in breast cancer prognosis. Methods: The study included 1503 breast cancer patients. Cancer-associated fibroblasts were identified using morphologic features from hematoxylin and eosin slides. The study analyzed clinicopathologic parameters, survival rates, immune cells, gene sets, and prognostic models using gene-set enrichment analysis, in silico cytometry, pathway analysis, in vitro drug-screening, and gradient-boosting machine (GBM)-learning. Results: The presence of CAFs correlated significantly with young age, lymphatic invasion, and perineural invasion. In silico cytometry showed altered leukocyte subsets in the presence of CAFs, with decreased CD8+ T cells. Gene-set enrichment analysis showed associations with critical processes such as the epithelial-mesenchymal transition and immune modulation. Drug sensitivity analysis in breast cancer cell lines with varying fibroblast activation protein-α expression suggested that CAF-targeted therapies might enhance the efficacy of certain anticancer drugs including ARRY-520, ispinesib-mesylate, paclitaxel, and docetaxel. Integrating CAF presence with machine-learning improved survival prediction. For breast cancer patients, CAFs were independent prognostic markers for worse disease-specific survival and disease-free survival. Conclusion: This study highlighted the significance of CAFs in breast cancer biology and provided compelling evidence of their impact on patient outcomes and treatment response. The findings offer valuable insights into the potential of CAFs as prognostic and predictive biomarkers and support the development of CAF-targeted therapies to improve breast cancer management. [ABSTRACT FROM AUTHOR]