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Abstract Background Zolgensma is a gene‐replacement therapy that has led to a promising treatment for spinal muscular atrophy (SMA). However, clinical trials of Zolgensma have raised two major concerns: insufficient therapeutic effects and adverse events. In a recent clinical trial, 30% of patients failed to achieve motor milestones despite pre‐symptomatic treatment. In addition, more than 20% of patients showed hepatotoxicity due to excessive virus dosage, even after the administration of an immunosuppressant. Here, we aimed to test whether a ubiquitination‐resistant variant of survival motor neuron (SMN), SMNK186R, has improved therapeutic effects for SMA compared with wild‐type SMN (SMNWT). Methods A severe SMA mouse model, SMA type 1.5 (Smn−/−; SMN2+/+; SMN∆7+/−) mice, was used to compare the differences in therapeutic efficacy between AAV9‐SMNWT and AAV9‐SMNK186R. All animals were injected within Postnatal Day (P) 1 through a facial vein or cerebral ventricle. Results AAV9‐SMNK186R‐treated mice showed increased lifespan, body weight, motor neuron number, muscle weight and functional improvement in motor functions as compared with AAV9‐SMNWT‐treated mice. Lifespan increased by more than 10‐fold in AAV9‐SMNK186R‐treated mice (144.8 ± 26.11 days) as compared with AAV9‐SMNWT‐treated mice (26.8 ± 1.41 days). AAV9‐SMNK186R‐treated mice showed an ascending weight pattern, unlike AAV9‐SMNWT‐treated mice, which only gained weight until P20 up to 5 g on average. Several motor function tests showed the improved therapeutic efficacy of SMNK186R. In the negative geotaxis test, AAV9‐SMNK186R‐treated mice turned their bodies in an upward direction successfully, unlike AAV9‐SMNWT‐treated mice, which failed to turn upwards from around P23. Hind limb clasping phenotype was rarely observed in AAV9‐SMNK186R‐treated mice, unlike AAV9‐SMNWT‐treated mice that showed clasping phenotype for more than 20 out of 30 s. At this point, the number of motor neurons (1.5‐fold) and the size of myofibers (2.1‐fold) were significantly increased in AAV9‐SMNK186R‐treated mice compared with AAV9‐SMNWT‐treated mice without prominent neurotoxicity. AAV9‐SMNK186R had fewer liver defects compared with AAV9‐SMNWT, as judged by increased proliferation of hepatocytes (P

Abstract Background Colon cancer ranks as the second most lethal form of cancer globally. In recent years, there has been active investigation into using the methylation profile of circulating tumor DNA (ctDNA), derived from blood, as a promising indicator for diagnosing and monitoring colon cancer. Results We propose a liquid biopsy-based epigenetic method developed by utilizing 49 patients and 260 healthy controls methylation profile data to screen and monitor colon cancer. Our method initially identified 901 colon cancer-specific hypermethylated (CaSH) regions in the tissues of the 49 cancer patients. We then used these CaSH regions to accurately quantify the amount of circulating tumor DNA (ctDNA) in the blood samples of these same patients, utilizing cell-free DNA methylation profiles. Notably, the methylation profiles of ctDNA in the blood exhibited high sensitivity (82%) and specificity (93%) in distinguishing patients with colon cancer from the control group, with an area under the curve of 0.903. Furthermore, we confirm that our method for ctDNA quantification is effective for monitoring cancer patients and can serve as a valuable tool for postoperative prognosis. Conclusions This study demonstrated a successful application of the quantification of ctDNA among cfDNA using the original cancer tissue-derived CaSH region for screening and monitoring colon cancer.

Fibro-adipogenic progenitors (FAPs) are muscle-resident mesenchymal progenitors that can contribute to muscle tissue homeostasis and regeneration, as well as postnatal maturation and lifelong maintenance of the neuromuscular system. Recently, traumatic injury to the peripheral nerve was shown to activate FAPs, suggesting that FAPs can respond to nerve injury. However, questions of how FAPs can sense the anatomically distant peripheral nerve injury and whether FAPs can directly contribute to nerve regeneration remained unanswered. Here, utilizing single-cell transcriptomics and mouse models, we discovered that a subset of FAPs expressing GDNF receptors Ret and Gfra1 can respond to peripheral nerve injury by sensing GDNF secreted by Schwann cells. Upon GDNF sensing, this subset becomes activated and expresses Bdnf. FAP-specific inactivation of Bdnf (Prrx1Cre; Bdnffl/fl) resulted in delayed nerve regeneration owing to defective remyelination, indicating that GDNF-sensing FAPs play an important role in the remyelination process during peripheral nerve regeneration. In aged mice, significantly reduced Bdnf expression in FAPs was observed upon nerve injury, suggesting the clinical relevance of FAP-derived BDNF in the age-related delays in nerve regeneration. Collectively, our study revealed the previously unidentified role of FAPs in peripheral nerve regeneration, and the molecular mechanism behind FAPs’ response to peripheral nerve injury.

Purpose This study aimed to develop the ultrasonography (US) criteria for risk stratification of the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) 4 nodules, and to evaluate the diagnostic yield of a modified biopsy criterion in a multicenter cohort. Methods In total, 1,542 K-TIRADS 4 nodules (≥1 cm) were included in the study. US criteria for the subcategorization of K-TIRADS 4 nodules were developed based on high-risk US features. The diagnostic yields and false referral rates of biopsy criterion 1 (size cut-off of 1 cm), biopsy criterion 2 (size cut-off of 1.5 cm), and modified biopsy criterion 3 (size cut-off of 1 cm for K-TIRADS 4B and 1.5 cm for K-TIRADS 4A) were evaluated. Results The five high-risk US features (solid composition, marked hypoechogenicity, macrocalcification, punctate echogenic foci, and irregular margin) independently increased the malignancy risk of the K-TIRADS 4 nodules (P

Abstract Small molecule can be utilized to restore the effectiveness of existing major classes of antibiotics against antibiotic‐resistant bacteria. In this study, it is demonstrated that celastrol, a natural compound, can modify the bacterial cell wall and subsequently render bacteria more suceptible to β‐lactam antibiotics. It is shown that celastrol leads to incomplete cell wall crosslinking by modulating levels of c‐di‐AMP, a secondary messenger, in methicillin‐resistant Staphylococcus aureus (MRSA). This mechanism enables celastrol to act as a potentiator, effectively rendering MRSA susceptible to a range of penicillins and cephalosporins. Restoration of in vivo susceptibility of MRSA to methicillin is also demonstrated using a sepsis animal model by co‐administering methicillin along with celastrol at a much lower amount than that of methicillin. The results suggest a novel approach for developing potentiators for major classes of antibiotics by exploring molecules that re‐program metabolic pathways to reverse β‐lactam‐resistant strains to susceptible strains.

The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing low-risk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression.

The ability to perform machine learning (ML) tasks in a database management system (DBMS) is a new paradigm for conventional database systems as it enables advanced data analytics on top of well-established capabilities of DBMSs. However, the integration of ML in DBMSs introduces new challenges in traditional CPU-based systems because of its higher computational demands and bigger data bandwidth requirements. To address this, hardware acceleration has become even more important in database systems, and the computational storage device (CSD) placing an accelerator near storage is considered as an effective solution due to its high processing power with no extra data movement cost. In this paper, we propose Trinity, an end-to-end database system that enables in-database, in-storage platform that accelerates advanced analytics queries invoking trained ML models along with complex data operations. By designing a full stack from DBMS’s internal software components to hardware accelerator, Trinity enables in-database ML pipelines on the CSD. On the software side, we extend the internals of conventional DBMSs to utilize the accelerator in the SmartSSD. Our extended analyzer evaluates the compatibility of the current query with our hardware accelerator and compresses compatible queries into a 24-byte numeric format for efficient hardware processing. Furthermore, the predictor is extended to integrate our performance cost models to always offload queries into the optimal hardware backend. The proposed SmartSSD cost model mathematically models our hardware, including host operations, data transfers, FPGA kernel execution time, and the CPU cost model uses polynomial regression ML models to predict complex CPU latency. On the hardware side, we introduce the in-database processing accelerator (i-DPA), a custom FPGA-based accelerator. i-DPA includes database page decoder to fully exploit the bandwidth benefit of near-storage processing. It also employs dynamic tuple binding to enhance the overall parallelism and hardware utilization. i-DPA;s architecture having heterogeneous computing units with a reconfigurable on-chip interconnect also allows seamless data streaming, enabling task-level pipeline across different computing units. Finally, our evaluation shows that Trinity improves the end-to-end performance of analytics queries by $15.21\times $ on average and up to $57.18\times $ compared to the conventional CPU-based DBMS platform. We also show that the Trinity’s performance can linearly scale up with multiple SmartSSDs, achieving nearly up to $200\times $ speedup over the baseline with four SmartSSDs.

Abstract Microplastics (MPs) is an escalating aquatic environmental crisis that poses significant threats to marine organisms, especially mussels. Here, we compare the cumulative toxic effects of the two most abundant morphotypes of MPs in the environment, microspheres, and microfibers, on the gill and digestive gland (DG) of Mytilus galloprovincialis in a dose-dependent (1, 10, and 100 mg/L) and time-dependent (1, 4, 7, 14, 21 days exposure) manner. DNA fragmentation assessment through TUNEL assay revealed consistency in the pattern of morphological disturbance degree and cell apoptosis proportions indicated by histopathological analysis. Upon the acute phase of exposure (day 1–4), gill and DG treated with low MPs concentration exhibited preserved morphology and low proportion of TUNEL+ cells. At higher concentrations, spherical and fibrous MP-induced structural impairments and DNA breakage occurred at distinct levels. 100 mg/L microfibers was lethal to all mussels on day 21, indicating the higher toxicity of the fibrous particles. During the chronic phase, both morphological abnormalities degree and DNA fragmentation level increased over time and with increasing concentration, but the differentials between the spherical and fibrous group was gradually reduced, particularly diminished in 10 and 100 mg/L in the last 2 weeks. Furthermore, analysis of transcriptional activities of key genes for apoptosis of 100 mg/L–day 14 groups revealed the upregulation of both intrinsic and extrinsic apoptotic induction pathway and increment in gene transcripts involving genotoxic stress and energy metabolism according to MP morphotypes. Overall, microfibers exert higher genotoxic effects on mussel. In response, mussels trigger more intense apoptotic responses together with enhanced energy metabolism to tolerate the adverse effects in a way related to the accumulation of stimuli.

Thyroid cancer, characterized by high incidence rates, good prognosis, and frequent recurrence, is typically treated surgically. However, since the early 2000s, radiofrequency ablation, which is commonly utilized in liver, lung, and kidney cancers, is being performed for management of primary and recurrent thyroid cancers. Many studies have focused on inoperable cases of low-risk papillary microcarcinoma (≤ 1 cm) and some have investigated its role in larger lesions (up to 4 cm). Overall, these studies have reported positive results. Radiofrequency ablation for recurrent cancer has primarily been performed for locally recurrent cervical cancer, and this therapeutic approach has been attempted for treatment of distant metastases in lungs and bones, with encouraging outcomes. A growing global trend, particularly in South Korea, the United States, and Europe supports radiofrequency ablation for thyroid cancer. However, this therapy is currently not recognized as a treatment option recommended by universally accepted clinical guidelines such as those established by the National Comprehensive Cancer Network. Based on past efforts and future research, radiofrequency ablation is expected to play a key role in thyroid cancer treatment in the near future.

Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules and recurrent thyroid cancers. In Korea, RFA for thyroid nodules was first performed in 2002, and a large population study was published in 2008. The Task Force Committee of the Korean Society of Thyroid Radiology (KSThR) developed its first recommendations for RFA in 2009, which were revised in 2012 and 2018. The KSThR guideline was the first guideline for RFA of thyroid nodules worldwide and has become a guideline for physicians to perform thyroid RFA in Korea and other countries around the world. These guidelines have contributed significantly to the establishment and widespread use of RFA worldwide. In addition, since 2015, the KSThR has conducted intensive hands-on courses depending on the level of the participants. In this article, the authors introduce the history of eduction for RFA conducted by the KSThR and describe the learning curve of RFA and current training programs in Korea, along with future directions for training programs.

Objectives This study aims to contribute to establishing the regional effective management of fine particulate matter by evaluating the chemical characteristics and contribution of fine particulate matter, and the accuracy of predictive model of fine particulate matter through the measurement of water-soluble inorganic ions (WSIIs) and electrical conductivity for fine particulate matter generated in Pohang. Methods PM10 and PM2.5 samples were simultaneously collected using a low volume air sampler from April to November 2022. For sample analysis, cations of Ca2+, Mg2+, K+, NH4+, Na+ and anions of Cl-, NO3-, SO42-, and electrical conductivity were measured after pretreatment by ultrasonic extraction. Results and Discussion The average concentrations of WSIIs for PM10 and PM2.5 in Pohang were 12.1μg/m3 and 8.5μg/m3, respectively, accounting for 35.5% and 50.0% of each fine particulate matter. The sum of NH4+, NO3-, SO42- concentration was found to account for the majority of 71% and 78% of WSIIs in PM10 and PM2.5, respectively. The PM2.5/PM10 ratios for NH4+, K+, and SO42- were 95%, 89%, and 81%, respectively, mostly present in PM2.5. The average ratio of PM2.5/PM10 for NO3- was 54%, but it rose sharply to 79% in November when the temperature was low, indicating an increase in contribution to the generation of PM2.5 in winter. During the sampling period excluding April and July, the ion balance for cations and anions was relatively good at a 1:1 ratio and showed chemical properties of fine particulate matter close to neutral. A regression model was evaluated for the measured electrical conductivity of WSIIs and the concentration of fine particulate matter. The MAE and RMSE values for PM2.5 were 1.8μg/m3 and 2.4μg/m3, respectively, which were lower than PM10 (MAE 7.5 μg/m3, RMSE 10.3μg/m3), indicating high precision and accuracy. Conclusion This study confirmed the origin of fine particulate matter generated in Pohang through WSIIs analysis, and suggested that the measured electrical conductivity of WSIIs could be used as a key parameter for measuring the concentration of fine particulate matter.

We investigated the geochemistry of gas, pore fluid, and methane-derived authigenic carbonate (MDAC) from four sites in the southern Ulleung Basin, South Korea. In contrast to Sites 16GH-P1 and 16GH-P5, Sites 16GH-P3, and 16GH-P4 are characterized by acoustic chimney structures associated with gas flux. The composition of gas and isotopic signatures of methane (CH4) (C1/C2+ > 300, δ13CCH4 < -60‰, δDCH4 ≤ -190‰) indicate microbial source CH4 at all sites. The upward migration of CH4 can affect the chemical and isotopic properties of pore fluid and gas-related byproducts (e.g., gas hydrate (GH) and MDAC) within the shallow sediments including the current sulfate-methane transition (SMT) (< 5 meters below seafloor). Although no GH was found, elevated Cl- concentrations (maximum = 609 mM) with low δD and δ18O values in Site 16GH-P4 pore fluids delineate the influence of massive GH formation in deeper sediment. In contrast, relatively constant Cl-, δD, and δ18O values in fluids from Sites 16GH-P1, 16GH-P3, and 16GH-P5 indicate a predominant origin from seawater. Pore fluids also exhibit higher concentrations of H4SiO4, B, Mg2+, and K+, along with increasing alkalinity compared to seawater. These observations suggest that marine silicate weathering alters fluid chemistry within the sediment, affecting element and carbon cycles. High alkalinity (up to 60 mM) and Mg2+/Ca2+ ratios (> 6) alongside decreasing Ca2+ and Sr2+ concentrations imply carbonate precipitation. MDACs with diverse morphologies, mainly composed of aragonite and magnesian calcite, and characterized by low carbon isotopic values (δ13CMDAC < -31.3‰), were found at Sites 16GH-P3 and 16GH-P4. Interestingly, δ13CMDAC values at Site 16GH-P3 are clearly differentiated above and below the current SMT. High δ13CMDAC values above the SMT (> -34.3‰) suggest the combined influence of seawater and CH4 migrating upward on MDAC precipitation, whereas low δ13CMDAC values below it (< -41.6‰) indicate a predominant impact of CH4 on MDAC formation. Additionally, the vertical variation of δ18OMDAC values at Site 16GH-P4, compared to the theoretical values, reflects an association with GH dissociation and formation. Our findings improve the understanding of fluid, gas, and MDAC geochemistry in continental margin cold seeps, providing insights into global carbon and element cycles.

BackgroundMany endolymphatic hydrops (EH) MRI studies in the literature do not include a normal control group. Consequently, it remains unclear which outcome measure in EH MRI can most effectively distinguish between MD patients and normal controls.MethodsGadolinium-enhanced EH imaging was performed to quantitatively evaluate the extents of hydrops in MD patients and age−/sex-matched normal controls. Four hours after intravenous injection of contrast agent, MRI was performed using a 3-T MR platform fitted with a 32-channel phased-array coil receptor. MR images (10–15 slices) covering an inner ear were 3D-stacked. Analyses of all images that included the vestibule or the cochlea yielded the volumes (in μL) of the endolymphatic and perilymphatic spaces.ResultsFor the vestibule, they were significantly greater EH% in ipsilateral (52.4 ± 12.5) than in contralateral MD ears (40.4 ± 8.5, p = 0.001) and in ipsilateral MD ears than in control ears (42.4 ± 13.7, p = 0.025). For the cochlea, the values were slightly higher EH% in ipsilateral MD ears (49.7 ± 10.4, p = 0.061) but did not significantly differ from contralateral (41.3 ± 12.6) or control ears (39.6 ± 18.9, p = 0.858). In the MD group, the EH asymmetries were 12.0 ± 10.2% (vestibule) and 8.4 ± 8.6% (cochlea), significantly larger than those of controls.ConclusionCompared to conventional semiquantitative grading or quantitative EH% analysis, EH asymmetry may better distinguish MD patients from normal controls. Quantitative hydrops volumetric analysis yields clinically relevant information on inner ear function.

Purpose This study evaluated thyroid cancer risk in a lung cancer screening population according to the presence of an incidental thyroid nodule (ITN) detected on low-dose chest computed tomography (LDCT). Methods Of 47,837 subjects who underwent LDCT, a lung cancer screening population according to the National Lung Screening Trial results was retrospectively enrolled. The prevalence of ITN on LDCT was calculated, and the ultrasonography (US)/fine-needle aspiration (FNA)–based risk of thyroid cancer according to the presence of ITN on LDCT was compared using the Fisher exact or Student t-test as appropriate. Results Of the 2,329 subjects (female:male=44:2,285; mean age, 60.9±4.9 years), the prevalence of ITN on LDCT was 4.8% (111/2,329). The incidence of thyroid cancer was 0.8% (18/2,329, papillary thyroid microcarcinomas [PTMCs]) and was higher in the ITN-positive group than in the ITN-negative group (3.6% [4/111] vs. 0.6% [14/2,218], P=0.009). Among the 2,011 subjects who underwent both LDCT and thyroid US, all risks were higher (P

(1) Background: Both intra-articular pathologies and muscle imbalance can be a cause of shoulder instability. The purpose of this study is to examine the cross-sectional areas of the rotator cuff muscle in patients with acute and chronic anterior shoulder instability and to determine the associations between imbalance and chronicity of the rotator cuff. (2) Methods: Patients with confirmed dislocation of the anterior shoulder were included. The patients were divided into two groups according to the time between the initial dislocation event and when MRI imaging was performed Measurements of the rotator cuff muscle areas were performed in the scapular Y view and glenoid face view using MRI. (3) Results: A total of 56 patients were enrolled. In the Y view, a larger area of supraspinatus muscle was observed in the chronic group compared with the acute group (17.2 ± 2.3% vs. 15.6 ± 2.2%, p = 0.006). However, a smaller area of subscapularis muscle was observed in the chronic group (47.1 ± 3.5% vs. 49.6 ± 5.3%, p = 0.044). Using the glenoid face view, a larger area of supraspinatus muscle was observed in the chronic group than in the acute group (18.5 ± 2.5% vs. 15.8 ± 2.2%, p < 0.001). However, a smaller area of subscapularis muscle was observed in the chronic group (41.6 ± 3.2% vs. 45.6 ± 4.4%, p < 0.001). (4) Conclusion: Larger areas of supraspinatus muscle compared with acute instability were observed in patients with chronic anterior shoulder instability. In contrast, a smaller area of subscapularis muscle was observed in the chronic group.

Recently, deep neural network (DNN) acceleration has been critical for hardware systems from mobile/edge devices to high-performance data centers. Especially, for on-device AI, there have been many studies on hardware numerical precision reduction considering the limited hardware resources of mobile/edge devices. Although layer-wise mixed-precision leads to computational complexity reduction, it is not straightforward to find a well-balanced layer-wise precision scheme since it takes a long time to determine the optimal precision for each layer due to the repetitive experiments and the model accuracy, the fundamental measure of deep learning quality, should be considered as well. In this paper, we propose the layer-wise mixed precision scheme which can significantly reduce the time required to determine the optimal hardware numerical precision with Signal-to-Quantization Noise Ratio (SQNR)-based analysis. In addition, the proposed scheme can take the hardware complexity into consideration in terms of the number of operations (OPs) or weight memory requirement of each layer. The proposed method can be directly applied to inference, meaning that users can utilize well-trained neural network models without the need for additional training or hardware units. With the proposed SQNR-based analysis, for SSDlite and YOLOv2 networks, the analysis time required for layer-wise precision determination is reduced by more than 95% compared to conventional mean Average Precision(mAP)-based analysis. Also, with the proposed complexity-aware schemes, the number of OPs and weight memory requirement can be reduced by up to 86.14% and 78.03%, respectively, for SSDlite, and by up to 51.93% and 50.62%, respectively, for YOLOv2, with negligible model accuracy degradation.

With the development of Internet networks, the PageRank algorithm, which was initially developed to recommend important pages in Google’s web search systems, is widely used as the basis of various ranking systems in graph processing fields. However, PageRank algorithm requires Sparse Matrix-Vector Multiplication (SpMV) repeatedly which becomes main bottleneck for the calculation. In this study, we present the multi-mode SpMV accelerator for half-to-single transprecision PageRank with real-world graphs. To support transprecision, where the operation performs in half-precision (FP16) initially and changes its precision to single-precision (FP32), the proposed multi-mode SpMV accelerator can perform both dual FP16 mode and single FP32 mode. In dual FP16 mode, the proposed accelerator performs two FP16 SpMV in parallel, and in single FP32 mode, it performs one FP32 SpMV with the same hardware resources. Also, for the reduction of memory footprint, the proposed accelerator supports the Compressed Sparse Row (CSR) format. In addition, dual-issue accumulator and multi-mode transprecision multiplier are presented to support both FP16 and FP32 modes. Validation of the proposed transprecision PageRank algorithm is performed with four real-world graph datasets, resulting in a low 0-4% error rate and $1.3\times $ - $1.9\times $ speedup compared to single-precision PageRank computation without transprecision.

Purpose Although the taller-than-wide (TTW) sign has been regarded as one of the most specific ultrasound (US) features of thyroid malignancy, uncertainty still exists regarding the US probe’s orientation when evaluating it. This study investigated which US plane would be optimal to identify the TTW sign based on malignancy risk stratification using a registry-based imaging dataset. Methods A previous study by 17 academic radiologists retrospectively analyzed the US images of 5,601 thyroid nodules (≥1 cm, 1,089 malignant and 4,512 benign) collected in the webbased registry of Thyroid Imaging Network of Korea through the collaboration of 26 centers. The present study assessed the diagnostic performance of the TTW sign itself and fine needle aspiration (FNA) indications via a comparison of four international guidelines, depending on the orientation of the US probe (criterion 1, transverse plane; criterion 2, either transverse or longitudinal plane). Results Overall, the TTW sign was more frequent in malignant than in benign thyroid nodules (25.3% vs. 4.6%). However, the statistical differences between criteria 1 and 2 were negligible for sensitivity, specificity, and area under the curve (AUC) based on the size effect (all P0.05, respectively). Conclusion A longitudinal US probe orientation provided little additional diagnostic value over the transverse orientation in detecting the TTW sign of thyroid nodules.

Purpose Using simulation in continuing professional development (CPD) courses for local practitioners is uncommon in Korea. The aim of our study was to evaluate the responses of the local practitioners for a simulation-based short CPD course. Methods Following the targeted needs assessment of local practitioners, we developed and implemented a 3-hour simulation-based CPD course for the first 5 minutes of cardiac arrest in the resource-limited local clinics. We evaluated the participant’s responses to the course using a questionnaire. Results During the 3-year implementation period, 115 practitioners participated in 10 courses, and 113 (98%) responded to the questionnaire. The overall course satisfaction (10-point scale) was very positive (10 in 93 [82.3%], 9 in 19 [16.8%], and 8 in 1 [0.8%]). The level (5-point scale) of recommendation to the others was also high (5 in 103 [91.2%] and 4 in 10 [8.8%]). Many participants positively commented on the authentic practical experience of the uncommon crisis in their contexts. Conclusion A simulation-based short CPD course for in-hospital cardiac arrest could provide an authentic practical experience for local practitioners working in resource-limited clinics.

Abstract Reverse total shoulder arthroplasty (RTSA) improves function and reduces pain for patients with complex shoulder problems. However, there is a lack of literature regarding the association of radiographic parameters on clinical outcomes after RTSA. The aim of this study was to analyze various radiographic parameters that may be predictive of clinical outcomes after RTSA. A total of 55 patients treated with RTSA were enrolled. Shoulder radiographic parameters were used for measurement of critical shoulder angle, acromial index, acromiohumeral interval, deltoid lever arm, acromial angulation, glenoid version, and acromial height. Preoperative and postoperative clinical outcomes were evaluated at a minimum 2-year follow-up. An analysis of correlations between radiographic parameters and clinical outcomes was then performed. A significant change in critical shoulder angle, acromiohumeral interval, and deltoid lever arm was observed between preoperative and postoperative radiographic measurements. A significant improvement was observed in all clinical outcomes and range of motions from preoperative to postoperative (all p

Abstract Various risk stratification systems show discrepancies in the ultrasound lexicon of nodule echotexture and hypoechogenicity. This study aimed to determine the malignancy risk of thyroid nodules according to their echotexture and degree of hypoechogenicity. From June to September 2015, we retrospectively evaluated 5601 thyroid nodules with final diagnoses from 26 institutions. Nodules were stratified according to the echotexture (homogeneous vs. heterogeneous) and degree of hypoechogenicity (mild, moderate, or marked). We calculated the malignancy risk according to composition and suspicious features. Heterogeneous hypoechoic nodules showed a significantly higher malignancy risk than heterogeneous isoechoic nodules (P ≤ 0.017), except in partially cystic nodules. Malignancy risks were not significantly different between homogeneous versus heterogeneous nodules in both hypoechoic (P ≥ 0.086) and iso- hyperechoic nodules (P ≥ 0.05). Heterogeneous iso-hyperechoic nodules without suspicious features showed a low malignancy risk. The malignancy risks of markedly and moderately hypoechoic nodules were not significantly different in all subgroups (P ≥ 0.48). Marked or moderately hypoechoic nodules showed a significantly higher risk than mild hypoechoic (P ≤ 0.016) nodules. The predominant echogenicity effectively stratifies the malignancy risk of nodules with heterogeneous echotexture. The degree of hypoechogenicity could be stratified as mild versus moderate to marked hypoechogenicity.

Purpose The aim of this multicenter study was to investigate the malignancy risk of minimally cystic thyroid nodules (MCTNs) using cyto-histopathologic diagnoses as the reference standard. Methods From June 2015 to September 2015, 5,601 thyroid nodules (≥1 cm) from 4,989 consecutive patients who underwent thyroid ultrasonography (US) at 26 institutions were retrospectively analyzed. Each thyroid nodule was categorized according to its cystic proportion: purely solid, minimally cystic (≤10%), and partially cystic (>10%). The malignancy risk of MCTNs was compared with those of purely solid nodules and partially cystic thyroid nodules (PCTNs). The malignancy risk of MCTNs was assessed according to echogenicity and the presence of suspicious US features. Results The prevalence of MCTNs was 22.5%. The overall malignancy risk of MCTNs was 8.8%, which was significantly lower than that of purely solid nodules (29.5%) (P0.05). MCTNs were associated with a higher risk of malignancy in hypoechoic nodules than in isohyperechoic nodules and in nodules with suspicious US features than in those without suspicious US features (all P

The sea-level rise during the Holocene (11–0 ky BP) and its resulting sedimentation and biogeochemical processes may control microbial life in Arctic sediments. To gain further insight into this interaction, we investigated a sediment core (up to 10.7 m below the seafloor) from the Chuckchi Shelf of the western Arctic Ocean using metabarcoding-based sequencing and qPCR to characterize archaeal and bacterial 16S rRNA gene composition and abundance, respectively. We found that Arctic Holocene sediments harbor local microbial communities, reflecting geochemical and paleoclimate separations. The composition of bacterial communities was more diverse than that of archaeal communities, and specifically distinct at the boundary layer of the sulfate–methane transition zone. Enriched cyanobacterial sequences in the Arctic middle Holocene (8–7 ky BP) methanogenic sediments remarkably suggest past cyanobacterial blooms. Bacterial communities were phylogenetically influenced by interactions between dispersal limitation and environmental selection governing community assembly under past oceanographic changes. The relative influence of stochastic and deterministic processes on the bacterial assemblage was primarily determined by dispersal limitation. We have summarized our findings in a conceptual model that revealed how changes in paleoclimate phases cause shifts in ecological succession and the assembly process. In this ecological model, dispersal limitation is an important driving force for progressive succession for bacterial community assembly processes on a geological timescale in the western Arctic Ocean. This enabled a better understanding of the ecological processes that drive the assembly of communities in Holocene sedimentary habitats affected by sea-level rise, such as in the shallow western Arctic shelves.

We present a proof-of-concept simulation-based inference on Ω _m and σ _8 from the Sloan Digital Sky Survey (SDSS) Baryon Oscillation Spectroscopic Survey (BOSS) LOWZ Northern Galactic Cap (NGC) catalog using neural networks and domain generalization techniques without the need of summary statistics. Using rapid light-cone simulations L- picola , mock galaxy catalogs are produced that fully incorporate the observational effects. The collection of galaxies is fed as input to a point cloud-based network, Minkowski-PointNet . We also add relatively more accurate G adget mocks to obtain robust and generalizable neural networks. By explicitly learning the representations that reduce the discrepancies between the two different data sets via the semantic alignment loss term, we show that the latent space configuration aligns into a single plane in which the two cosmological parameters form clear axes. Consequently, during inference, the SDSS BOSS LOWZ NGC catalog maps onto the plane, demonstrating effective generalization and improving prediction accuracy compared to non-generalized models. Results from the ensemble of 25 independently trained machines find Ω _m = 0.339 ± 0.056 and σ _8 = 0.801 ± 0.061, inferred only from the distribution of galaxies in the light-cone slices without relying on any indirect summary statistics. A single machine that best adapts to the G adget mocks yields a tighter prediction of Ω _m = 0.282 ± 0.014 and σ _8 = 0.786 ± 0.036. We emphasize that adaptation across multiple domains can enhance the robustness of the neural networks in observational data.

We introduce a GPU-accelerated hybrid hydro/ N -body code ( Enzo-N ) designed to address the challenges of concurrently simulating star clusters and their parent galaxies. This task has been exceedingly challenging, primarily due to the considerable computational time required, which stems from the substantial scale difference between galaxies (∼0.1 Mpc) and star clusters (∼parsecs). Yet, this significant scale separation means that particles within star clusters perceive those outside the star cluster in a semistationary state. By leveraging this aspect, we integrate a direct N -body code ( Nbody6++GPU ) into a cosmological (magneto)hydrodynamic code ( Enzo ) through utilization of the semistationary background acceleration approximation. We solve the dynamics of particles within star clusters using a direct N -body solver with regularization for few-body interactions, while evolving particles outside—dark matter, gas, and stars—using a particle-mesh gravity solver and hydrodynamic methods. We demonstrate that Enzo-N successfully simulates the coevolution of star clusters and their parent galaxies, capturing phenomena such as core collapse of the star cluster and tidal stripping due to galactic tides. This comprehensive framework opens up new possibilities for studying the evolution of star clusters within galaxies, offering insights that were previously inaccessible.

In this fourth paper from the AGORA Collaboration, we study the evolution down to redshift z = 2 and below of a set of cosmological zoom-in simulations of a Milky Way mass galaxy by eight of the leading hydrodynamic simulation codes. We also compare this CosmoRun suite of simulations with dark matter-only simulations by the same eight codes. We analyze general properties of the halo and galaxy at z = 4 and 3, and before the last major merger, focusing on the formation of well-defined rotationally supported disks, the mass–metallicity relation, the specific star formation rate, the gas metallicity gradients, and the nonaxisymmetric structures in the stellar disks. Codes generally converge well to the stellar-to-halo mass ratios predicted by semianalytic models at z ∼ 2. We see that almost all the hydro codes develop rotationally supported structures at low redshifts. Most agree within 0.5 dex with the observed mass–metallicity relation at high and intermediate redshifts, and reproduce the gas metallicity gradients obtained from analytical models and low-redshift observations. We confirm that the intercode differences in the halo assembly history reported in the first paper of the collaboration also exist in CosmoRun , making the code-to-code comparison more difficult. We show that such differences are mainly due to variations in code-dependent parameters that control the time stepping strategy of the gravity solver. We find that variations in the early stellar feedback can also result in differences in the timing of the low-redshift mergers. All the simulation data down to z = 2 and the auxiliary data will be made publicly available.

Dark-matter-deficient galaxies (DMDGs) discovered in the survey of ultra-diffuse galaxies (UDGs), in apparent conflict with standard cold dark matter, may be produced by high-velocity galaxy–galaxy collisions, the so-called Mini-Bullet scenario. Recent observations of an aligned trail of 7–11 UDGs near NGC 1052, including DMDGs DF2 and DF4, suggesting a common formation event, ∼8.9 ± 1.5 Gyr ago, provide a test.Hydro/ N -body simulations, supplemented by galaxy orbit integrations, demonstrate that satellite–satellite collisions outside the host-galaxy virial radius can reproduce the observed UDGs in the NGC 1052 group. A trail of ∼10 DMDGs is shown to form, including 2 massive ones that replicate the observed motions of DF2 and DF4. The linear relation, v = A x + v _0 , conjectured previously to relate positions ( x ) and velocities ( v ) of the aligned DMDGs as a signature of the collision event, is approximately obeyed, but individual DMDGs can deviate significantly from it. The progenitors whose collision spawned the trail of DMDGs survive the collision without themselves becoming DMDGs. We predict that one progenitor is located at the end of the trail, which can be tested by observing the difference between its stars, formed pre-collision, from those of the DMDGs, formed post-collision. By contrast, stellar ages and metallicities of the DMDGs are nearly identical. We further offer a hint that the tidal field of host NGC 1052 may contribute to making DMDGs diffuse. ΛCDM simulation in a 100 cMpc box finds our required initial conditions ∼10 times at z < 3. These results indicate current observations are consistent with the Mini-Bullet scenario.

We introduce a novel halo/galaxy matching technique between two cosmological simulations with different resolutions, which utilizes the positions and masses of halos along their subhalo merger tree. With this tool, we conduct a study of resolution biases through the galaxy-by-galaxy inspection of a pair of simulations that have the same simulation configuration but different mass resolutions, utilizing a suite of IllustrisTNG simulations to assess the impact on galaxy properties. We find that, with the subgrid physics model calibrated for TNG100-1, subhalos in TNG100-1 (high resolution) have ≲0.5 dex higher stellar masses than their counterparts in the TNG100-2 (low resolution). It is also discovered that the subhalos with M _gas ∼ 10 ^8.5 M _⊙ in TNG100-1 have ∼0.5 dex higher gas mass than those in TNG100-2. The mass profiles of the subhalos reveal that the dark matter masses of subhalos in TNG100-2 converge well with those from TNG100-1, except within 4 kpc of the resolution limit. The differences in stellar mass and hot gas mass are most pronounced in the central region. We exploit machine learning to build a correction mapping for the physical quantities of subhalos from low- to high-resolution simulations (TNG300-1 and TNG100-1), which enables us to find an efficient way to compile a high-resolution galaxy catalog even from a low-resolution simulation. Our tools can easily be applied to other large cosmological simulations, testing and mitigating the resolution biases of their numerical codes and subgrid physics models.

We analyze and compare the satellite halo populations at z ∼ 2 in the high-resolution cosmological zoom-in simulations of a 10 ^12 M _⊙ target halo ( z = 0 mass) carried out on eight widely used astrophysical simulation codes ( Art-I , Enzo , Ramses , Changa , Gadget-3 , Gear , Arepo-t , and Gizmo ) for the AGORA High-resolution Galaxy Simulations Comparison Project. We use slightly different redshift epochs near z = 2 for each code (hereafter “ z ∼ 2”) at which the eight simulations are in the same stage in the target halo’s merger history. After identifying the matched pairs of halos between the CosmoRun simulations and the DMO simulations, we discover that each CosmoRun halo tends to be less massive than its DMO counterpart. When we consider only the halos containing stellar particles at z ∼ 2, the number of satellite galaxies is significantly fewer than that of dark matter halos in all participating AGORA simulations and is comparable to the number of present-day satellites near the Milky Way or M31. The so-called “missing satellite problem” is fully resolved across all participating codes simply by implementing the common baryonic physics adopted in AGORA and the stellar feedback prescription commonly used in each code, with sufficient numerical resolution (≲100 proper pc at z = 2). We also compare other properties such as the stellar mass–halo mass relation and the mass–metallicity relation. Our work highlights the value of comparison studies such as AGORA, where outstanding problems in galaxy formation theory are studied simultaneously on multiple numerical platforms.

We analyze the circumgalactic medium (CGM) for eight commonly-used cosmological codes in the AGORA collaboration. The codes are calibrated to use identical initial conditions, cosmology, heating and cooling, and star formation thresholds, but each evolves with its own unique code architecture and stellar feedback implementation. Here, we analyze the results of these simulations in terms of the structure, composition, and phase dynamics of the CGM. We show properties such as metal distribution, ionization levels, and kinematics are effective tracers of the effects of the different code feedback and implementation methods, and as such they can be highly divergent between simulations. This is merely a fiducial set of models, against which we will in the future compare multiple feedback recipes for each code. Nevertheless, we find that the large parameter space these simulations establish can help disentangle the different variables that affect observable quantities in the CGM, e.g., showing that abundances for ions with higher ionization energy are more strongly determined by the simulation’s metallicity, while abundances for ions with lower ionization energy are more strongly determined by the gas density and temperature.

Skeletal muscle is now regarded as an endocrine organ based on its secretion of myokines and exerkines, which, in response to metabolic stimuli, regulate the crosstalk between the skeletal muscle and other metabolic organs in terms of systemic energy homeostasis. This conceptual basis of skeletal muscle as a metabolically active organ has provided insights into the potential role of physical inactivity and conditions altering muscle quality and quantity in the development of multiple metabolic disorders, including insulin resistance, obesity, and diabetes. Therefore, it is important to understand human muscle physiology more deeply in relation to the pathophysiology of metabolic diseases. Since monolayer cell lines or animal models used in conventional research differ from the pathophysiological features of the human body, there is increasing need for more physiologically relevant in vitro models of human skeletal muscle. Here, we introduce recent studies on in vitro models of human skeletal muscle generated from adult myogenic progenitors or pluripotent stem cells and summarize recent progress in the development of three-dimensional (3D) bioartificial muscle, which mimics the physiological complexity of native skeletal muscle tissue in terms of maturation and functionality. We then discuss the future of skeletal muscle 3D-organoid culture technology in the field of metabolic research for studying pathological mechanisms and developing personalized therapeutic strategies.

The advancement of quantum computing threatens the security of conventional public-key cryptosystems. Post-quantum cryptography (PQC) was introduced to ensure data confidentiality in communication channels, and various algorithms are being developed. The National Institute of Standards and Technology (NIST) has initiated PQC standardization, and the selected algorithms for standardization and round 4 candidates were announced in 2022. Due to the large memory footprint and highly repetitive operations, there have been numerous attempts to accelerate PQC on both hardware and software. This paper introduces the RISC-V instruction set extension for NIST PQC standard algorithms and round 4 candidates. The proposed programmable crypto-processor can support a wide range of PQC algorithms with the extended RISC-V instruction set and demonstrates significant reductions in code size, the number of executed instructions, and execution cycle counts of target operations in PQC algorithms of up to 79%, 92%, and 87%, respectively, compared to RV64IM with optimization level 3 (-O3) in the GNU toolchain.

Abstract To compare free-water corrected diffusion tensor imaging (DTI) measures in the normal-appearing periependymal area between AQP4-IgG-seropositive NMOSD and multiple sclerosis (MS) to investigate occult pathophysiology. This prospective study included 44 patients (mean age, 39.52 ± 11.90 years; 14 men) with AQP4-IgG-seropositive NMOSD (n = 20) and MS (n = 24) who underwent DTI between April 2014 and April 2020. Based on free-water corrected DTI measures obtained from normal-appearing periependymal voxels of (1) lateral ventricles and (2) the 3rd and 4th ventricles as dependent variables, MANCOVA was conducted to compare the two groups, using clinical variables as covariates. A significant difference was found between AQP4-IgG-seropositive NMOSD and MS in the 3rd and 4th periependymal voxels (λ = 0.462, P = 0.001). Fractional anisotropy, axial diffusivity was significantly decreased and radial diffusivity was increased in AQP4-IgG-seropositive NMOSD in post-hoc analysis, compared with MS (F = 27.616, P

(1) Background: Patients with a superior-labrum-from-anterior-to-posterior (SLAP) tear associated with a spinoglenoid ganglion cyst have undergone various procedures. The purpose of this study is to evaluate clinical outcomes following arthroscopic treatment in patients with a concomitant spinoglenoid ganglion cyst and SLAP lesion. (2) Methods: This study followed PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, utilizing the PubMed, EMBASE, Cochrane Library, and Scopus databases. The keywords included shoulder, SLAP, labral tear, spinoglenoid notch, paralabral cyst, arthroscopy, and treatment. (3) Results: A total of 14 articles (206 patients) were included. Repair alone was administered in 114 patients (Group R), and 92 patients underwent additional cyst decompression (Group RD). Both groups showed excellent and similar clinical scores. The rate of the complete resorption of the cyst was 95.5% in Group RD, and 92.2% in Group R. The complication rate was 3.5% in Group RD, and 11.4% in Group R. The reoperation rate was 0% in Group RD, and 5.3% in Group R. (4) Conclusion: Reliable clinical outcomes without serious complications were obtained from the use of both procedures. The decompression of the cyst is a safe method that will alleviate pressure on the suprascapular nerve.

Abstract Background Pseudolarix kaempferi is a traditional Chinese natural product that possesses the potential cytotoxic effects against cancer. However, the precise molecular mechanism underlying its cytotoxic effects has not yet been completely elucidated. Here, we clarify the mechanism via which the ethanol extract of P. kaempferi (EEPK) leads to cytotoxicity mediated by apoptosis in mucoepidermoid carcinoma (MEC) originating from the salivary glands. Methods We investigated the mechanism underlying the anticancer efficacy of EEPK in human MEC in vitro by assessing mitochondrial dysfunction, mRNA levels, and morphological changes in apoptotic cell nuclei as well as by using a cytotoxicity assay, flow cytometric analysis, and western blotting. Results EEPK inhibited the growth of two human MEC cells and stimulated the induction of caspase-mediated apoptosis that was accompanied by mitochondrial membrane depolarization. Compared with the vehicle control groups, EEPK decreased myeloid cell leukemia-1 (Mcl-1) expression in both cells whereas it significantly decreased B cell lymphoma-2 (Bcl-2) expression in MC3 cells only. The EEPK-induced altered Mcl-1 expression was caused by translational inhibition and proteasomal degradation. Additionally, EEPK significantly increased p-Bcl-2 (Ser70) expression regardless of its total forms by facilitating the activation of the c-Jun N-terminal kinase (JNK) signaling pathway, which exhibited cell context dependency. Nevertheless, JNK activation following EEPK treatment was, at least in part, required for the proapoptotic efficacy of EEPK in both cells. Conclusions This study revealed that EEPK-induced alterations of Mcl-1 inhibition and JNK/Bcl-2 phosphorylation cause apoptosis and provided basic preclinical data for future clinical trials regarding therapy for patients with MEC. Graphic abstract

Abstract This study aimed to investigate the efficacy of the combination of neuron-specific enolase (NSE) measurement and initial neurological examination in predicting the neurological outcomes of patients with cardiac arrest (CA) by retrospectively analyzing data from the Korean Hypothermia Network prospective registry. NSE levels were recorded at 48 and 72 h after CA. The initial Full Outline of UnResponsiveness (FOUR) and Glasgow Coma Scale (GCS) scores were recorded. These variables were categorized using the scorecard method. The primary endpoint was poor neurological outcomes at 6 months. Of the 475 patients, 171 (36%) had good neurological outcomes at 6 months. The areas under the curve (AUCs) of the categorized NSE levels at 72 h, GCS score, and FOUR score were 0.889, 0.722, and 0.779, respectively. The AUCs of the combinations of categorized NSE levels at 72 h with categorized GCS scores and FOUR score were 0.910 and 0.912, respectively. Each combination was significantly higher than the AUC value of the categorized NSE level at 72 h alone (with GCS: p = 0.015; with FOUR: p = 0.026). Combining NSE measurement and initial neurological examination improved the prediction of neurological outcomes.

Purpose We aimed to identify the factors associated with the repeated febrile seizures (RFS), defined as recurrent seizures during the same febrile illness. Methods We reviewed the medical records of children with febrile seizure who visited 4 academic emergency departments from October 2016 through September 2018. Differences were identified in variables regarding clinical and laboratory characteristics between the children with and without RFS. The RFS was the primary outcome. Logistic regression was conducted to identify factors associated with the occurrence of RFS. Results Among 1,551 children, 922 were included in the study, of whom, 198 (21.5%) underwent RFS. Of the children with RFS, 188 (94.9%) underwent the recurrences within the initial 24 hours. Logistic regression showed focal seizure (adjusted odds ratio, 6.67; 95% confidence interval, 2.37-18.82), venous pH < 7.31 (5.89; 3.13-11.08), and postictal drowsiness > 30 minutes (1.90; 1.30-2.78) as the factors for RFS. Conclusion In children with febrile seizure, focal seizure, acidosis, and prolonged postictal state may be independent risk factors for RFS. These findings may be informed to healthcare professionals and parents caring for children with febrile seizure.

Lithium (Li) has two stable isotopes, 6Li and 7Li, whose large relative mass difference is responsible for significant isotopic fractionation during physico-chemical processes, allowing Li isotopes to be a good tracer of continental chemical weathering. Although physical erosion is dominant in the Polar regions due to glaciers, increasing global surface temperature may enhance chemical weathering, with possible consequences on carbon biogeochemical cycle and nutriment flux to the ocean. Here, we examined elemental and Li isotope geochemistry of meltwaters, suspended sediments, soils, and bedrocks in the Barton Peninsula, King George Island, Antarctica. Li concentrations range from 8.7 nM to 23.3 μM in waters, from 0.01 to 1.43 ppm in suspended sediments, from 9.56 to 36.9 ppm in soils, and from 0.42 to 28.3 ppm in bedrocks. δ7Li values are also variable, ranging from +16.4 to +41.1‰ in waters, from −0.4 to +13.4‰ in suspended sediments, from −2.5 to +6.9‰ in soils, and from −1.8 to +11.7‰ in bedrocks. Elemental and Li isotope geochemistry reveals that secondary phase formation during chemical weathering mainly control dissolved δ7Li values, rather than a mixing with sea salt inputs from atmosphere or ice melting. Likewise, δ7Li values of suspended sediments and soils lower than those of bedrocks indicate modern chemical weathering with mineral neoformation. This study suggests that increasing global surface temperature enhances modern chemical weathering in Antarctica, continuing to lower δ7Li values in meltwater with intense water-rock interactions.

We investigated the pore fluid and methane-derived authigenic carbonate (MDAC) chemistry from the ARAON Mounds in the Chukchi Sea to reveal how methane (CH4) seepage impacts their compositional and isotopic properties. During the ARA07C and ARA09C Expeditions, many in situ gas hydrates (GHs) and MDACs were found near the seafloor. The fluid chemistry has been considerably modified in association with the high CH4 flux and its related byproducts (GHs and MDACs). Compared to Site ARA09C-St 08 (reference site), which displays a linear SO42- downcore profile, the other sites (e.g., ARA07C-St 13, ARA07C-St 14, ARA09C-St 04, ARA09C-St 07, and ARA09C-St 12) that are found byproducts exhibit concave-up and/or kink type SO42- profiles. The physical properties and fluid pathways in sediment columns have been altered by these byproducts, which prevents the steady state condition of the dissolved species through them. Consequently, chemical zones are separated between bearing and non-bearing byproducts intervals under non-steady state condition from the seafloor to the sulfate-methane transition (SMT). GH dissociation also significantly impacts pore fluid properties (e.g., low Cl-, enriched δD and δ18O). The upward CH4 with depleted δ13C from the thermogenic origin affects the chemical signatures of MDACs. The enriched δ18O fluid from GH dissociation also influences the properties of MDACs. Thus, in the ARAON Mounds, the chemistry of the fluid and MDAC has significantly changed, most likely responding to the CH4 flux and GH dissociation through geological time. Overall, our findings will improve the understanding and prediction of the pore fluid and MDAC chemistry in the Arctic Ocean related to CH4 seepage by global climate change.

Abstract. Background/Aims:. Studies showed that remote device monitoring reduced unnecessary outpatient visits and increased patient satisfaction. As there was no local research on remote monitoring (RM) in Korea, there was a lack of evidence for policy or insurance standards due to the lack of domestic data despite high demand by domestic arrhythmia experts. To establish the basis for patient satisfaction, economic efficiency, and safety of wireless monitoring, a survey-based study was planned. Methods:. This was a single-university hospital survey. The satisfaction index was evaluated using a questionnaire to investigate patient satisfaction in outpatient clinics, economic efficiency (measured as home-to-clinic time, waiting time, and actual clinic time), and demand for RM in patients with implantable cardiac devices. The questionnaire was adopted and modified from the Survey on Telehealth Patient Experience by Bas-Villalobos, 2006 (modified Korean version 2.0 by You Mi Hwang, 2020). Results:. Surveys were answered by 171 patients. The mean age of these patients was 71.2 ± 12.4 years. Based on the survey, home to clinic time was usually less than one h, mean waiting time in the hospital until clinic time ranged 42.6 ± 24.5 minutes, and mean clinic time ranged 3.1 ± 1.7 minutes. Based on the survey, patients favored RM over hospital visits with cardiac implantable electronic device follow-up mainly because of long travel times from home to clinic. Conclusion:. Based on the survey results, there is a clear need for RM in patients who have cardiac implantable electronic devices.

Purpose To explore cerebrovascular reservoir (CVR) and arterial transit time (ATT) changes using acetazolamide-challenged multi-phase arterial spin labeling (MP-ASL) perfusion-weighted MRI in chronic cerebrovascular steno-occlusive disease. Materials and Methods This retrospective study enrolled patients with chronic steno-occlusion who underwent acetazolamide-challenged MP-ASL between June 2019 and October 2020. Cerebral blood flow, CVR, basal ATT, and ATT changes associated with severe stenosis, total occlusion, and chronic infarction lesions were compared. Results There were 32 patients (5 with bilateral steno-occlusion) in our study sample. The CVR was significantly reduced during total occlusion compared with severe stenosis (26.2% ± 28.8% vs. 41.4% ± 34.1%, respectively, p = 0.004). The ATT changes were not significantly different (p = 0.717). The CVR was marginally lower in patients with chronic infarction (29.6% ± 39.1% vs. 38.9% ± 28.7%, respectively, p = 0.076). However, the ATT was less shortened in patients with chronic infarction (-54 ± 135 vs. -117 ± 128 ms, respectively, p = 0.013). Conclusion Acetazolamide-challenged MP-ASL provides an MRI-based CVR evaluation tool for chronic steno-occlusive disease.

Abstract Glioblastoma remains the most devastating brain tumor despite optimal treatment, because of the high rate of recurrence. Distant recurrence has distinct genomic alterations compared to local recurrence, which requires different treatment planning both in clinical practice and trials. To date, perfusion-weighted MRI has revealed that perfusional characteristics of tumor are associated with prognosis. However, not much research has focused on recurrence patterns in glioblastoma: namely, local and distant recurrence. Here, we propose two different neural network models to predict the recurrence patterns in glioblastoma that utilizes high-dimensional radiomic profiles based on perfusion MRI: area under the curve (AUC) (95% confidence interval), 0.969 (0.903–1.000) for local recurrence; 0.864 (0.726–0.976) for distant recurrence for each patient in the validation set. This creates an opportunity to provide personalized medicine in contrast to studies investigating only group differences. Moreover, interpretable deep learning identified that salient radiomic features for each recurrence pattern are related to perfusional intratumoral heterogeneity. We also demonstrated that the combined salient radiomic features, or “radiomic risk score”, increased risk of recurrence/progression (hazard ratio, 1.61; p = 0.03) in multivariate Cox regression on progression-free survival.

Complete tear of the posterior medial meniscus root can result in a loss of hoop tension and increased contact pressure. Thus, medial meniscus posterior root tear (MMPRT) is increasingly recognized as an important pathology. Although several surgical techniques for MMPRT have recently been introduced, the ideal technique is not yet established. This technical note is aimed at introducing a novel surgical technique using two transtibial tunnels with modified Mason–Allen stitches in the treatment of MMPRT.

Abstract Background With organismal aging, the hypothalamic–pituitary–gonadal (HPG) activity gradually decreases, resulting in the systemic functional declines of the target tissues including skeletal muscles. Although the HPG axis plays an important role in health span, how the HPG axis systemically prevents functional aging is largely unknown. Methods We generated muscle stem cell (MuSC)‐specific androgen receptor (Ar) and oestrogen receptor 2 (Esr2) double knockout (dKO) mice and pharmacologically inhibited (Antide) the HPG axis to mimic decreased serum levels of sex steroid hormones in aged mice. After short‐term and long‐term sex hormone signalling ablation, the MuSCs were functionally analysed, and their aging phenotypes were compared with those of geriatric mice (30‐month‐old). To investigate pathways associated with sex hormone signalling disruption, RNA sequencing and bioinformatic analyses were performed. Results Disrupting the HPG axis results in impaired muscle regeneration [wild‐type (WT) vs. dKO, P

Muscle atrophy is associated with ageing, but the underlying molecular mechanisms are not well understood. Here, they authors show that ablation of the E3 ubiquitin ligase Mib1 is important for myofibre maintenance via a mechanism that involves targeting and degradation of Actn3, and that Mib1 ablation in mice induces muscle atrophy which can be rescued by knockown of Actn3 expression.

Radiofrequency ablation (RFA) is a thermal ablation technique widely used for the management of benign thyroid nodules. To date, five academic societies in various countries have reported clinical practice guidelines, opinion statements, or recommendations regarding the use of thyroid RFA. However, despite some similarities, there are also differences among the guidelines, and a consensus is required regarding safe and effective treatment in Asian countries. Therefore, a task force was organized by the guideline committee of the Asian Conference on Tumor Ablation with the goal of devising recommendations for the clinical use of thyroid RFA. The recommendations in this article are based on a comprehensive analysis of the current literature and the consensus opinion of the task force members.

Radiofrequency ablation (RFA) is a thermal ablation technique widely used for the management of benign thyroid nodules. To date, five academic societies in various countries have reported clinical practice guidelines, opinion statements, or recommendations regarding the use of thyroid RFA. However, despite some similarities, there are also differences among the guidelines, and a consensus is required regarding safe and effective treatment in Asian countries. Therefore, a task force was organized by the guideline committee of the Asian Conference on Tumor Ablation with the goal of devising recommendations for the clinical use of thyroid RFA. The recommendations in this article are based on a comprehensive analysis of the current literature and the consensus opinion of the task force members.

The adrenal gland plays a pivotal role in an organism’s health span by controlling the endocrine system. Decades of research on the adrenal gland have provided multiscale insights into the development and maintenance of this essential organ. A particularly interesting finding is that founder stem/progenitor cells participate in adrenocortical development and enable the adult adrenal cortex to regenerate itself in response to hormonal stress and injury. Since major advances have been made in understanding the dynamics of the developmental process and the remarkable regenerative capacity of the adrenal gland, understanding the mechanisms underlying adrenal development, maintenance, and regeneration will be of interest to basic and clinical researchers. Here, we introduce the developmental processes of the adrenal gland and discuss current knowledge regarding stem/progenitor cells that regulate adrenal cortex remodeling and regeneration. This review will provide insights into the fascinating ongoing research on the development and regeneration of the adrenal cortex.