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Background: Sphingolipids play a crucial role in cellular functions and are essential components of cell membranes, signaling molecules, and lipid metabolism. In particular, ceramide is a key intermediate in sphingolipid metabolism and defects in ceramide metabolism can lead to various inborn errors of metabolism, making ceramides important targets for clinical screening and diagnosis. Detecting altered concentration patterns of sphingolipids is desirable for distinguishing related inborn errors of metabolism for diagnosis and treatment monitoring., Methods: We developed a liquid chromatography-tandem mass spectrometry method with a pathway-oriented approach to focus on sphingolipids involved in ceramide metabolism. A total of 47 sphingolipids bearing different head groups and side chains were targeted. Precision/reproducibility, linearity, and spike recovery extraction efficiency tests were performed on plasma and serum samples from confirmed cases of sphingolipidosis., Results: Linearity of the method showed the coefficient of determination (r2) for all standards to be >0.99 with a slope of 1.00 ± 0.01. Intra- and interday reproducibility of standards spiked into plasma and serum revealed a coefficient of variation <20%. Spike and recovery assessment showed recovery values of 80%-120% for all standards. Altered levels of sphingolipids from patients with hereditary sensory and autonomic neuropathy caused by pathogenic variants in SPTLC2 and hypomyelinating leukodystrophy related to variants in DEGS1 were detected, in agreement with trends reported in earlier studies confirming the utility of this pathway-centric method., Conclusions: This method can serve as a useful tool to simultaneously monitor sphingolipids, enabling screening and diagnosis of inborn errors of ceramide metabolism., (© Association for Diagnostics & Laboratory Medicine 2024.)

Background: Ruptured pseudoaneurysm of the distal anterior inferior cerebellar artery (AICA) in patients with a history of gamma knife surgery (GKS) for vestibular schwannoma (VS) is rare. Several previous reports have described treatment strategies for radiation-induced pseudoaneurysm in the AICA: either surgical trapping or endovascular parent artery occlusion of the AICA. Methods: We present the first case of endosaccular coil embolization for a ruptured pseudoaneurysm in a large-diameter AICA after GKS for VS, successfully preserving the parent AICA. Results: Major recanalization of the coiled pseudoaneurysm was observed on follow-up imaging 3 months after the initial endovascular treatment. The patient subsequently underwent additional endosaccular coil embolizations for regrowth of the treated pseudoaneurysm buried in the VS. Two years later, another major recanalization was detected, prompting further retreatment. Subsequently, the patient has remained in a stable condition for 4 years. Conclusions: We suggest that endosaccular coil embolization of the distal AICA aneurysm with parent artery preservation might be a safe and feasible treatment option for radiation-induced saccular pseudoaneurysm arising from a large parent artery. However, close and regular follow-up imaging and preparation for potential retreatment are necessary, as pseudoaneurysms coiled within VSs are prone to recanalization.

The analysis of gangliosides and glycosphingolipids is crucial for understanding cellular membrane structure and function as well as to accurately diagnose certain inborn errors of metabolism. GM2-gangliosidosis represents a rare and fatal group of lysosomal storage disorders characterized by accumulation of GM2 gangliosides in various tissues and organs. These disorders arise due to deficiency or functional impairment of the β-hexosaminidase A or B enzymes, which are responsible for degradation of GM2 ganglioside. Deficient enzyme activity primarily leads to the accumulation of GM2 gangliosides within the lysosomes of cells. Accurate and rapid diagnostic methods that detect increased levels of GM2 gangliosides in patients with GM2-gangliosidosis can play a significant role in early diagnosis and appropriate treatment of this condition. To address this need, we developed a multiplexed liquid chromatography-tandem mass spectrometry method targeting 84 species of gangliosides and other glycosphingolipids involved in ganglioside metabolism. Reproducibility, linearity, extraction efficiency, and sample stability were evaluated and proof-of-concept data obtained from analysis of serum samples from confirmed cases of GM2-gangliosidosis. This method has the potential to simultaneously monitor the biosynthesis of gangliosides and the lysosomal catabolic pathway serving as a valuable tool for screening and diagnosing an important group of lysosomal storage disorders., (© 2024. The Author(s).)

This article presents a numerical platform for predicting the performance of paper-based analytical devices. The capillary flow, reaction, dissolution, and other physicochemical phenomena associated with device operation are accounted for using Darcy's law, Richard's equation and other transport equations. The platform can be used for different paper substrates, biorecognition methods, detection systems (such as optical and electrochemical detection), device patterns and dimensions, and ways in which the device is operated such as the input method of the body fluid. The device performance is quantified using indicators such as assay time, signal strength and product cost. The predictive capability of this numerical tool is verified with devices reported in the literature. It is shown that the platform can be used to identify possible improvements to these existing devices. More importantly, it can also serve as a numerical tool for synthesizing new paper-based analytical devices with minimum experimental effort.

Background: In general, venous aneurysm associated with dural arteriovenous fistula (dAVF) is considered to be developed under long standing venous hypertension and manifested as venous ectasia of draining vein itself. However, discrete saccular shaped venous aneurysm without angiographic evidence of venous hypertension arising from the draining vein, like cerebral arterial aneurysm, is quite rare and its pathomechanism remains unclear in patients with dAVF., Case Summary: In this report, we present two cases of ruptured saccular venous aneurysms associated with dAVF without venous hypertension or venous ectasia. In both cases, significant curve or stenosis is observed in draining vein, which is located in just distal portion of the venous aneurysms. These aneurysms were successfully treated with a transarterial embolization. Underlying mechanism of venous aneurysms in these cases is discussed., Conclusion: Although there is little doubt that hemodynamic stress has a critical role in the development of venous aneurysms in patients with dAVF, preceding venous hypertension or venous ectasia is not necessary for development and enlargement of venous aneurysms. Considering the significant risk of rupture, a careful review of draining vein features including tortuosity or stenosis is needed, especially in venous aneurysms without evidence of venous hypertension., Competing Interests: Conflict-of-interest statement: There is no conflict-of-interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Endovascular therapy (EVT) is the treatment of choice for acute ischemic stroke (AIS) with large vessel occlusion. However, in many patients, successful EVT recanalization does not correspond to a clinical improvement, called futile recanalization (FR). We aimed to identify stroke risk factors and patient characteristics associated with FR in AIS with large core infarct (LCI)., Methods: A total of 137 patients with AIS with LCI treated by EVT at a single stroke center were retrospectively included from January 2016 to June 2023. LCI was defined by Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECT) < 6. Patient age, sex, modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), time to treatment, risk factors, and radiologic findings were collected, and potential associations with FR were analyzed. FR was defined as successful reperfusion with modified Thrombolysis in Cerebral Infarction (mTICI) ≥ 2b but without functional independence at 90 days (mRS ≥ 3). A multivariate logistic regression analysis was conducted on the clinical characteristics of patients, based on the presence or absence of FR, and the factors influencing FR., Results: Of 137 patients, 120 showed successful recanalization (mTICI ≥ 2b). All patients were divided into FR (n = 80) and no FR (n = 40) groups. Older age (odds ratio [OR] 1.052, 95% confidence interval [CI] 1.002-1.105; p = 0.041), the higher the initial NIHSS score (OR 1.181, 95% CI 1.037-1.344; p = 0.012), and prior intravenous plasminogen activator (OR 0.310, 95% CI 0.118-0.813, p = 0.017) were independent influencing factors of FR., Conclusions: The older age, the higher the initial NIHSS, and not receiving intravenous plasminogen activator were independently associated with FR in AIS with LCI. These factors could identify poor responders to EVT recanalization., (© 2024. The Author(s).)

Background: Lung cancer, a leading global cause of cancer-related mortality, necessitates enhanced prognostic markers for improved treatment outcomes. We have previously shown a tumor suppressive role of cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1), which is targeted for degradation upon phosphorylation at S14 (pCASTOR1) in multiple types of cancer. This study focuses on the predictive value of pCASTOR1 in lung adenocarcinoma (LUAD) patients with KRAS mutations., Results: Employing a newly developed pCASTOR1 specific antibody, we found that tumor cells exhibited significantly elevated pCASTOR1 scores compared to non-tumor cells (P < 0.05). Higher pCASTOR1 scores predicted poorer overall survival (OS) (HR = 3.3, P = 0.0008) and relapse-free survival (RFS) (HR = 3.0, P = 0.0035) in male patients with KRAS mutations. pCASTOR1 remained an independent predictor for OS (HR = 4.1, P = 0.0047) and RFS (HR = 3.5, P = 0.0342) after controlling for other factors. Notably, in early-stage LUAD, elevated pCASTOR1 scores were associated with significantly worse OS (HR = 3.3, P = 0.0176) and RFS (HR = 3.1, P = 0.0277) in male patients with KRAS mutations, akin to late-stage patients., Conclusion: Elevated pCASTOR1 scores serve as biomarkers predicting poorer OS and RFS in male LUAD patients with KRAS mutations, offering potential clinical utility in optimizing treatment strategies for this subgroup., (© 2024. The Author(s).)

Objectives: This study aimed to identify radiologic features that differentiate lymphoma from metastasis manifesting as a solid enhancing mass lacking necrosis in the cerebellum. Methods: Pathologically confirmed 24 primary central nervous system lymphoma (PCNSL) and 32 metastasis patients with solid enhancing cerebellar masses without necrotic or hemorrhagic components were retrospectively analyzed. We evaluated the imaging characteristics using contrast-enhanced magnetic resonance imaging (MRI). The serrate sign was defined as a tumor spreading along white matter with branch-like enhancement or outward spikes. Results: The serrate sign was exclusively identified in the PCNSL group, showing a significant difference compared to the metastasis group (75.0% vs. 0%, p < 0.001). Homogeneous enhancement occurred more frequently in PCNSL than in metastasis (91.7% vs. 21.9%, p < 0.001). Conversely, bulging contour (62.5% vs. 4.2%, p < 0.001) and surface involvement (71.9% vs. 29.2%, p = 0.003) were more prevalent in metastasis than PCNSL. For predicting PCNSL, the serrate sign demonstrated 75.0% sensitivity, 100% specificity, 100% positive predictive value, 84.2% negative predictive value, and 89.3% accuracy. Conclusions: This study found that the serrate sign and homogeneous enhancement are reliable MRI features for differentiating cerebellar PCNSL from metastasis, whereas a bulging contour and surface involvement suggest metastasis. The serrate sign demonstrated diagnostic significance in differentiating PCNSL from metastasis.

Background: The inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC) is a complex disease with multifactorial etiology. The intestinal dysbiosis have been investigated to play an important role in IBD pathogenesis and disease activity. The aim of our study was to analyze the intestinal microbiota composition in IBD across different severity levels and the impact of biologic therapy on microbiota modulation., Methods: In this study, 27 IBD patients were recruited, including 14 patients undergoing biologic therapy for moderate to severe disease activity and 13 controls with inactive disease. The gut microbial composition was determined by 16 S ribosomal RNA gene sequencing of stool samples., Results: Biologic therapy led to significant clinical improvement in IBD disease activity after 48 weeks. About species richness, community alpha diversity was significant lower in active CD patients and enriched gradually after biologic therapy. The beta-diversity regard to the difference of bacterial community composition showed significant difference between patients in biologic and control group. A decrease in Firmicutes and increase in Bacteroidetes abundance were observed in patients with active disease, both in CD and UC. Biologic treatment induced shifts in gut microbiota, with increased Firmicutes and decreased Bacteroidetes, as well as improved F/B ratio gradually after treatment, correlating with disease activity., Conclusions: Our study suggested that gut microbiota differences changed after biologic therapies among IBD with different disease activity, and a rising Firmicutes/Bacteroidetes ratio could be a potential predictor for disease activity and treatment response monitoring., Competing Interests: Declaration of competing interest All authors declared there was no conflict of interests., (Copyright © 2024. Published by Elsevier B.V.)

Nitrogen (N) management is the key to achieving food security and environmental sustainability. Here we analyse N flows using a localized N management model for wheat, maize and rice in 1,690 Chinese counties, with a breakdown of multiple reactive N (Nr) loss pathways. Results show that the total N input for producing these three staple crops in China was 22.2 Tg N in 2015, of which 7.4 Tg N was harvested as grain N and 4.0 Tg N was Nr losses in the forms of NH 3 (47%), NO x (10%), N 2 O (3%), and leaching and runoff (40%). By assuming a production level equivalent to that of the top 10% of counties with the highest N use efficiency and yields surpassing the regional average, we reveal the possibility of achieving national staple crop production targets while improving net ecosystem economic benefit in 2050 through a 49% reduction (10.4 Tg N) in synthetic N fertilizer inputs and a 52% decrease (2.9 Tg N) in Nr losses., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Remimazolam is not only associated with a lower incidence of respiratory depression than propofol but also in itself has the risk of respiratory depression., Objective: We investigated respiratory depression following remimazolam infusion, targeting different effect-site concentrations using target-controlled infusion., Design: A prospective, double-blind, randomised controlled study., Setting: Tertiary hospital, Suwon, South Korea, from April 2022 to November 2022., Participants: One hundred and seven patients scheduled for general anaesthesia were randomised into three groups targeting remimazolam effect-site concentrations of 500 (RMZ-500) ( n  = 36), 1000 (RMZ-1000) ( n  = 35) and 1500 ng ml -1 (RMZ-1500) ( n  = 36)., Interventions: Remimazolam was solely infused for 10 min according to target effect-site concentrations. According to the degree of SpO 2 decrease, oxygen desaturations were managed with the following respiratory supports: jaw-thrust for SpO 2 less than 97%, 100% oxygen delivery for SpO 2 less than 93% and assisted ventilation for SpO 2 less than 90%., Main Outcome Measures: The incidence of each respiratory support, along with respiratory variables (at baseline, 5 min and 10 min after remimazolam infusion) and loss of consciousness were observed for 10 min after remimazolam target-controlled infusion., Results: Both RMZ-1000 and RMZ-1500 required more frequent respiratory support than RMZ-500 (both P  < 0.001), with nearly identical frequencies between RMZ-1000 and RMZ-1500. In terms of respiratory support, the incidence of assisted ventilation was significantly lower in RMZ-500 (2.8%) than RMZ-1000 (48.6%) and RMZ-1500 (50%) ( P  < 0.001). RMZ-1000 and RMZ-1500 achieved loss of consciousness in all patients; RMZ-500 only achieved loss of consciousness in 86.1% of patients ( P  = 0.010). In patients who maintained spontaneous respiration, tidal volume decreased by 41 to 48% and respiratory rate increased by 118 to 158% at 5 and 10 min, significantly compared to baseline in all groups ( P  < 0.001)., Conclusions: Remimazolam infusion, like that of other benzodiazepines, led to respiratory depression, which was more prominent at higher target effect-site concentrations. Therefore, appropriate countermeasures should be developed to prevent oxygen desaturation., Trial Registration: CRIS ( https://cris.nih.go.kr ), identifier: KCT0006952., (Copyright © 2024 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

The operation of modern wastewater treatment facilities is a balancing act in which a multitude of variables are controlled to achieve a wide range of objectives, many of which are conflicting. This is especially true within secondary activated sludge systems, where significant research and industry effort has been devoted to advance control optimization strategies, both domain-driven and data-driven. Among data-driven control strategies, reinforcement learning (RL) stands out for its ability to achieve better than human performance in complex environments. While RL has been applied to activated sludge process optimization in existing literature, these applications are typically limited in scope, and never for the control of more than three actions. Expanding the scope of RL control has the potential to increase the optimization potential while concurrently reducing the number of control systems that must be tuned and maintained by operations staff. This study examined several facets of the implementation of multi-action, multi-objective RL agents, namely how many actions a single agent could successfully control and what extent of environment data was necessary to train such agents. This study observed improved control optimization with increasing action scope, though control of waste activated sludge remains a challenge. Furthermore, agents were able to maintain a high level of performance under decreased observation scope, up to a point. When compared to baseline control of the Benchmark Simulation Model No. 1 (BSM1), an RL agent controlling seven individual actions improved the average BSM1 performance metric by 8.3 %, equivalent to an annual cost savings of $40,200 after accounting for the cost of additional sensors., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Henry Croll reports financial support was provided by Iowa Water Environment Association. Henry Croll reports financial support was provided by Iowa Wastewater and Waste-to-Energy Research Program. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Adventitial cystic disease (ACD), a rare vascular disease characterized by mucus accumulation in the adventitia of blood vessels, typically affects the popliteal artery. We present the case of a 61-year-old female diagnosed with ACD in 2018 who was initially treated with endovascular stenting and percutaneous aspiration of the cyst. The patient, who had been asymptomatic for 5 years, developed a stent fracture and pseudoaneurysm requiring surgical intervention. Despite initial successful treatment, complications such as stent fracture and recurrence can occur; therefore, surgical treatment is recommended to optimize outcomes in patients with ACD. Endovascular treatment and cyst aspiration should only be considered in cases with high surgical risk. After treatment, long-term follow-up and individualized management strategies are important to monitor ACD recurrence.

Chili (Capsicum annuum L.) is an economically important crop worldwide, valued for its culinary uses. In South Korea, anthracnose caused by Colletotrichum spp. including C. truncatum, C. gloeosporioides, C. coccodes, C. acutatum, and C. scovillei incurs on substantial economic loss (Kim et al. 2008; Oo and Oh 2020). In August 2022, somewhat different types of symptoms that was not typical on chilli fruits were observed in a field in Yereonggwang (GPS: 35.2579° N, 126.4742° E), South Korea. The disease symptoms appeared as sunken, necrotic lesions with dense black spore masses forming in concentric rings. The estimated disease incidence the 0.2 ha field showing up to 1% of fruits affected. To isolate the pathogen, six symptomatic chilli fruits were collected. Small pieces (5 mm²) were cut from the margins of the lesions, surface-sterilized in 70% ethanol for 30 sec, followed by 1% sodium hypochlorite for 1 minute, and then rinsed three times in sterile distilled water. The tissue pieces were placed on potato dextrose agar (PDA) plates and incubated at 25°C in the dark. After 3 to 5 days, emerging fungal colonies were sub-cultured to obtain pure isolates. A total of five isolates were obtained and initially identified as Colletotrichum spp. based on morphological characteristics. Seven-day old colonies were initially white, turning light orange with age on PDA. Setae (observed on lesion) were dark brown, verruculose and septate. Conidia were cylindrical, hyaline, and measured 14.8 to 19.9 × 4.2 to 6.5 µm (mean 16.7 × 5.6 μm, n = 70) in size; appressoria were brown to dark brown and irregularly shaped. These morphological characteristics of the isolates agree with those reported for the morphology of C. sojae by Damm et al. (2019). To confirm the identity of the isolates, DNA was extracted and specific gene regions were amplified and sequenced using the following primer sets: ITS (ITS1 and ITS4), GAPDH (GDF1 and GDR1), ACT (ACT-512F and ACT-783R), TUB (T1 and Bt2b), HIS3 (CYLH3F and CYLH3R), and CHS-1 (CHS-79F and CHS-345R). The resulting sequences were deposited in the NCBI GenBank with accession numbers (LC830742 to LC830766). Maximum likelihood phylogenetic analysis using combine sequences of ITS, GAPDH, ACT, TUB, HIS3 and CHS-1 in MEGA X confirmed the isolates as C. sojae, marking the first report of this pathogen on chilli in South Korea, previously known to infect soybean. Pathogenicity tests were conducted on wound and nonwounded healthy and mature-green chili fruits (cv. Bicksita) to confirm the pathogenicity of the isolated C. sojae. The fruits were surface-sterilized using 70% ethanol and then rinsed with sterile distilled water. The fruits were wounded using a sterile needle to facilitate infection. A conidial suspension (1x106 conidia/mL) was prepared from 7-day-old PDA cultures. Each fruit was inoculated by placing a 10 µL drop of the conidial suspension onto the wounded and nonwounded sites (4 to 5) of the wound and unwound fruits, respectively. Control fruits were inoculated with sterile water. A total of 40 fruits per treatment were used and the experiment repeated twice. The fruits were placed in plastic box lined with moist paper towels to maintain high humidity and incubated at 25°C. Anthracnose symptoms developed on the inoculated fruits within 7 days, while control and unwounded fruits remained symptom-free. Colletotrichum sojae was successfully reisolated from the symptomatic fruits, fulfilling Koch's postulates and confirming its role as the causal agent of the disease. Colletotrichum sojae is known to infect Fabaceae species worldwide such as Glycine max, Medicago sativa, Phaseolus vulgaris, Atractylodes ovata and Vigna unguiculata (Damm et al. 2019; Talhinhas and Baroncelli 2021), Atractylodes ovata in South Korea (Hassan et al. 2021) and chili pepper in China (Zhanget al. 2023). The first report of C. sojae causing chili anthracnose in South Korea represents a new challenge for chili growers. Integrated disease management strategies need to be developed and implemented to mitigate its impact.

Variability between human pluripotent stem cell (hPSC) lines remains a challenge and opportunity in biomedicine. In this study, hPSC lines from multiple donors were differentiated toward neuroectoderm and mesendoderm lineages. We revealed dynamic transcriptomic patterns that delineate the emergence of these lineages, which were conserved across lines, along with individual line-specific transcriptional signatures that were invariant throughout differentiation. These transcriptomic signatures predicted an antagonism between SOX21-driven forebrain fates and retinoic acid-induced hindbrain fates. Replicate lines and paired adult tissue demonstrated the stability of these line-specific transcriptomic traits. We show that this transcriptomic variation in lineage bias had both genetic and epigenetic origins, aligned with the anterior-to-posterior structure of early mammalian development, and was present across a large collection of hPSC lines. These findings contribute to developing systematic analyses of PSCs to define the origin and consequences of variation in the early events orchestrating individual human development., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Burn injuries, affecting local skin disruption as well as inducing systemic inflammatory responses, are presented as a global public health problem. To enhance the effects of burn wound healing, treatment must simultaneously regulate both re-epithelialization and hyperinflammation. Extracts of Sargassum horneri ( S. horneri ) have shown a potential to enhance skin wound healing through antioxidative properties, immune enhancement, and modulation of inflammatory responses. However, despite its promising application for burn wound healing, specific investigation into S. horneri -derived compounds for enhancing wound healing has not yet been conducted. In this research, we investigated the burn wound-healing effect of the low-temperature pulverization-specific S. horneri extract (LPSHE), which could not be detected using the room-temperature grinding method. In a mouse burn model with third-degree burn injuries, LPSHE accelerated re-epithelialization by promoting the increase in F-actin formation and reduced burn-induced ROS levels. Additionally, LPSHE significantly regulated hyperinflammation by reducing pro-inflammatory cytokines. Further investigation into molecular mechanisms using HaCaT keratinocytes also demonstrated beneficial effects on burn wound healing. Taken together, our findings suggested that LPSHE is a promising therapeutic candidate for enhancing burn wound healing. Furthermore, this research underscored the importance of low-temperature pulverization in discovering novel natural compounds from marine organisms., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Obesity is the one of the most important components of metabolic syndrome. Because obesity related hypertension accounts for two thirds of essential hypertension, managing obesity and metabolic syndrome is a crucial task in the management of hypertension. However, the current non-pharmacological therapies have limitations for achieving or maintaining ideal body weight. Recently, glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated excellent weight control effects, accompanied by corresponding reductions in blood pressure. GLP1-RAs have shown cardiovascular and renal protective effects in cardiovascular outcome trials both in primary and secondary prevention. In this document, the Korean Society of Hypertension intends to remark the current clinical results of GLP1-RAs and recommend the government and health-policy makers to define obesity as a disease and to establish forward-looking policies for GLP1-RA treatment for obesity treatment, including active reimbursement policies., (© 2024. The Author(s).)

GLABRA1 (GL1), which encodes an R2R3 MYB transcription factor, is a key regulator of trichome patterning in the aerial organs of Arabidopsis (Arabidopsis thaliana). Although it has been generally assumed that GL1 functions exclusively in shoots and is not expressed in roots, reverse transcription polymerase chain reaction (RT-PCR) analysis has revealed that GL1 is indeed expressed in roots. To investigate whether GL1 plays a role in root epidermal patterning, we analyzed the effects of gl1 mutations in sensitized genetic backgrounds. Our findings show that gl1 mutants enhance the root epidermal phenotype of a weak allele of the werewolf (wer) mutant and suppress the phenotype of the caprice (cpc) mutant. We also demonstrate that the GL1 promoter is active in N-position epidermal cells, and that the GFP-GL1 fusion protein is predominantly localized in the nucleus of N-position cells. Furthermore, we provide evidence that GL1 expression is positively regulated by WER, GLABRA3, ENHANCER OF GLABRA3, and TRANSPARENT TESTA GLABRA1, while negatively regulated by CPC, TRIPTYCHON, and GLABRA2 (GL2). Notably, GL2, which is positively regulated by GL1, moderately represses GL1 expression, and both GL1 and GL2 are positively regulated by WER in N-position cells. These findings suggest that a negative feedback regulation of GL1 expression via GL2 contributes to the fine-tuning of non-hair cell fate determination in Arabidopsis root epidermis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Venoactive drugs (VADs) based on Vitis vinifera extract are widely used in Korea. However, studies on the clinical effects and head-to-head comparisons with other groups of VADs are limited. This trial aimed to evaluate whether Vitis vinifera seed extract was noninferior to the micronized purified flavonoid fraction (MPFF) in relieving venous symptoms and improving quality of life in patients with chronic venous disease., Methods: In this double-blind prospective randomized trial, patients from 13 hospitals, who were diagnosed with venous incompetence by duplex ultrasound and classified as clinical class 1, 2, or 3 in the Clinical, Etiological, Anatomical, and Pathophysiological classifications were enrolled. The primary outcome was the change in the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) score at 8 weeks from baseline. Secondary outcomes included changes in the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score at 4 and 8 weeks from baseline. Moreover, the change in leg circumferences was measured at 8 weeks and compared to baseline., Results: In total, 303 patients were enrolled and randomly assigned to receive either Vitis vinifera seed extract (n = 154) or MPFF (n = 149). The CIVIQ-20 scores at 8 weeks were significantly reduced compared to those at baseline in both groups. No significant intergroup difference in the change of CIVIQ-20 at 8 weeks from baseline was observed (-8.31 ± 14.63 vs. -10.35 ± 14.38, P = 0.29, 95% confidence interval -1.65 to 5.72). The lower limit of the 95% confidence interval was within the predefined noninferiority margin of 6.9. Furthermore, the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score scores significantly decreased at 4 and 8 weeks after randomization compared with baseline in both groups. No significant differences were observed in the reduction of each score between groups. The calf circumference measured at 8 weeks was significantly reduced compared to that at baseline in patients receiving Vitis vinifera seed extract., Conclusions: Vitis vinifera seed extract was noninferior to MPFF in relieving venous symptoms and improving the quality of life in patients with chronic venous disease., (Copyright © 2024. Published by Elsevier Inc.)

Objective: This study aimed to explore the perceptions and experiences of individuals that currently smoke and healthcare professionals on using real-time video counseling in the Smoking Cessation and Counselling Program in General Out-patient Clinics in Hong Kong., Design: This was a qualitative study using face-to-face semi-structured interviews based on the extended technology acceptance model. All interviews were audiotaped and transcribed verbatim. Two investigators coded the transcripts independently. Thematic analysis was adopted., Participants: Individuals that currently smoke and healthcare professionals who had experience using real-time video counseling in the Smoking Cessation and Counselling Program in General Out-patient Clinics in Hong Kong were recruited. Purposive sampling was adopted. 18 participants were interviewed to reach data saturation., Main Outcome Measures: Themes that emerged from thematic analysis of data were the main outcome measures. The emerged themes were refined and verified via inductive and then deductive processes until data saturation was reached., Results: Two core themes, which were in coherence with the extended technology acceptance model, namely (i) perceived ease of use and (ii) perceived usefulness, were identified. Under perceived ease of use, we identified 2 subthemes: (i) convenience and (ii) measures to facilitate the use of real-time video counseling. Three subthemes were identified under perceived usefulness: (i) empathy and rapport, (ii) measures for pandemics, and (iii) service outcome., Conclusion: Our study provided a culture-specific perspective of users towards real-time video counseling. It identified users' opinions on the easiness and usefulness of the service. Those could provide clues for future improvement and development of using real-time video counseling in healthcare services., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

This study investigated whether differences in survival rates and clinical outcomes exist in patients undergoing TKA by insurance type: National Health Insurance (NHI) vs. Medical Aid Program (MAP). This study conducted a retrospective analysis of 762 TKAs (NHI, n = 505; MAP, n = 257) with a mean follow-up of 8.4 ± 1.8 years. Patient-reported outcomes (PROMs) were evaluated using the American Knee Society's (AKS) score at the final follow-up. The survival rate of each group was analyzed using Kaplan-Meier survival analysis. Any postoperative complications and readmissions within 90 days of discharge were recorded and compared between the groups. There were no between-group differences in pre- to postoperative improvement in AKS scores. The estimated 10-year survival rates were 98.5% in the NHI group and 96.9% in the MAP group, respectively, with no significant differences ( p = 0.48). However, the length of hospital stay (LOS) was significantly longer in the MAP group than in the NHI group (13.4 days vs. 13.1 days, p = 0.03), and the transfer rate to other departments was significantly higher in the MAP group than in the NHI group (3.9% vs. 1.4%, p = 0.04). Readmission rates for orthopedic complications for 90 days were 3.0% in the NHI group and 3.5% in the MAP group, respectively ( p = 0.67). Patients' insurance type showed similar survival rates and clinical outcomes to those of primary TKA at a mean follow-up of 8.4 years, but the LOS and rate of transfer to other departments during hospitalization were influenced by insurance type.

Background: The rapid increase of minimally invasive surgery and the shortened training period for surgical residents has resulted in limited opportunities to acquire proficiency in open surgical techniques, such as vascular anastomosis. However, vascular anastomosis remains an essential skill in every surgery for bleeding control. This study aimed to validate the effectiveness of surgical education model for vascular anastomosis and assess the impact on the comprehension, skill, and confidence of surgical residents in performing vascular anastomosis., Methods: A total of 21 surgical residents with first to third years of experience at Seoul National University Hospital participated in a 4-week vascular anastomosis training program. The program included an educational lecture and the performance of an end-to-side anastomosis on a procedural model, with evaluations being conducted using the Objective Structured Assessment of Technical Skills (OSATS) and the End-Product Rating Score (EPRS) in pretraining and posttraining surveys., Results: Significant improvement was observed in the OSATS score (from 9.22 ± 2.4 in week 1 to 12.87 ± 3.1 in week 4; P < 0.001) and the EPRS score (from 12.47 ± 4.1 in week 1 to 17.57 ± 2.2 in week 4; P < 0.001). Additionally, the surgical performance time significantly decreased from 20.99 ± 4.6 min to 16.33 ± 4.2 min (P = 0.019) CONCLUSIONS: Simulator training of in vitro vascular anastomosis, when accompanied by expert-led instruction, can effectively enhance the surgical proficiency, confidence, and overall surgical outcomes of residents, as inferred from the observed improvements in OSATS and EPRS scores. The results suggest that integration of this training model into surgical curricula could be a promising strategy for enhancing vascular surgical training., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: This study aimed to assess metabolic changes to monitor the progression from normal liver to hepatitis B virus (HBV)-related hepatitis and liver fibrosis using hyperpolarized 13 C magnetic resonance imaging (MRI)., Procedures: Hepatitis was induced in mice (n = 16) via hydrodynamic injection of HBV 1.2 plasmid (25 μg). Among them, liver fibrosis was induced in the mice (n = 8) through weight-adapted administration of thioacetamide with ethanol. Normal control mice (n = 8) were injected with a phosphate buffer solution. Subsequently, a hyperpolarized 13 C MRI was performed on the mouse liver in vivo. The level of hepatitis B surface antigen (HBsAg) in blood serum was measured. Statistical analysis involved comparing the differential metabolite ratios, blood biochemistry values, and body weight among the three groups using the Kruskal-Wallis one-way analysis of variance., Results: HBsAg was absent in the normal and fibrosis groups, while it was detected in the hepatitis group. The ratios of [1- 13 C] lactate/pyruvate, [1- 13 C] alanine/pyruvate, [1- 13 C] lactate/total carbon, and [1- 13 C] alanine/total carbon were significantly lower in the normal control group than in the hepatitis and fibrosis groups (p < 0.05). Moreover, these ratios were significantly higher in the fibrosis group than in the hepatitis group (p < 0.05). However, no significant differences were observed in either [1- 13 C] pyruvate-hydrate/pyruvate or [1- 13 C] pyruvate-hydrate/total carbon among the three groups., Conclusions: The levels of [1- 13 C] lactate and [1- 13 C] alanine in vivo may serve as valuable indicators for differentiating between HBV-related hepatitis, liver fibrosis, and normal liver., (© 2024. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Background: High-dose dual therapy (HDDT) using proton-pump inhibitors (PPI) and amoxicillin attracted attention for its simplicity and lower adverse event profile. Besides, vonoprazan is not available worldwide. This real-world study aims to compare the efficacy of esomeprazole-based and rabeprazole-based HDDT regimens and to identify clinical factors influencing outcomes., Methods: A retrospective study enrolled 346 Helicobacter pylori-infected naïve patients from January 2016 to August 2023. Patients were assigned to either a 14-day esomeprazole-based HDDT (EA-14; esomeprazole 40 mg t.i.d. and amoxicillin 750 mg q.i.d. for 14 days, n = 173) or a 14-day rabeprazole-based HDDT (RA-14; rabeprazole 20 mg and amoxicillin 750 mg q.i.d. for 14 days, n = 173)., Results: Five patients from the EA-14 group and 10 from the RA-14 group were lost to follow-up, resulting in 168 and 163 patients for the per-protocol (PP) analysis, respectively. Eradication rates for the EA-14 and RA-14 groups were 90.2% and 80.9% (P = 0.014) in intention-to-treat (ITT) analysis; and 92.9% and 85.9% (P = 0.039) in PP analysis. Adverse event rates were similar between the two groups (11.9% vs 11.7%, P = 0.944). In multiple logistic regression analysis, age≧60 was associated with eradication failure (P = 0.046) and a trend of significance for smoking (P = 0.060) in the EA-14 group but not in the RA-14 group. A trend of significance was also observed for eradication regimens (EA-14 vs RA-14) (P = 0.071). The antibiotic resistance rates were amoxicillin (2.3%), clarithromycin (14.7%), metronidazole (40.3%), and dual resistance to clarithromycin and metronidazole (7.0%)., Conclusions: Esomeprazole-based HDDT achieved over 90% eradication rates but rabeprazole-based HDDT, which failed., Competing Interests: Declaration of competing interest All authors declared there was no conflict of interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Kidney transplantation is a widely used treatment for end-stage kidney disease. Nevertheless, the incidence of acute kidney injury (AKI) in deceased donors poses a potential hazard because it significantly increases the risk of delayed graft function and potentially exerts an influence on the kidney allograft outcome. It is crucial to develop a diagnostic model capable of assessing the existence and severity of AKI in renal grafts. However, no suitable kidney injury markers have been developed thus far., Methods: We evaluated the efficacy of the molecular probe NPO-B, which selectively responds to cysteine, as a new diagnostic tool for kidney injury. We used an in vitro model using ischemia/reperfusion injury human kidney-2 cells and an in vivo ischemia/reperfusion injury mouse model. Additionally, cysteine was investigated using urine samples from deceased donors and living donors to assess the applicability of detection techniques to humans., Results: This study confirmed that the NPO-B probe effectively identified and visualized the severity of kidney injury by detecting cysteine in both in vitro and in vivo models. We observed that the fluorescence intensity of urine samples measured using NPO-B from the deceased donors who are at a high risk of renal injury was significantly stronger than that of the living donors., Conclusions: If implemented in clinical practice, this new diagnostic tool using NPO-B can potentially enhance the success rate of kidney transplantation by accurately determining the extent of AKI in renal grafts., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Anthracnose, a destructive fungal disease, poses a significant threat to chili pepper (Capsicum annuum L.) production worldwide (de Silva et al. 2019). In South Korea, anthracnose outbreaks have traditionally been attributed to several Colletotrichum species such as C. gloeosporioides and C. acutatum. About 10% of the yield (chili production) is lost annually in South Korea due to chili anthracnose (Oo et al. 2020). During field surveys conducted in August 2017, symptomatic lesions resembling anthracnose were observed on chili pepper in two farmer's fields (Gochang and Cheongyang) in South Korea. Affected fruits exhibited characteristic symptoms, including circular sunken lesions with dark margins and abundant orange spore masses on the surface. About 20% of chili pepper fruit were affected in each field with an area of about 0.2 ha. Five putative Colletotrichum spp. isolates were obtained from six affected fruits (three from each field) following the procedure described by Cai et el. (2009). Three isolates (C01049, C01111, and C01115), representing each location, were selected to identify at the species level. Colonies on potato dextrose agar (incubated at 25°C in the dark for 7 days) were cottony with entire margins, white aerial mycelium and dark gray in the center. Conidia were hyaline, aseptate, cylindrical with bothnds round, and 17.8 - 30.5 × 6.0 -10.0 µm (mean 23.8 ×7.9 μm, n = 30). Appressoria were dark brown, irregular but mostly ovoid with smooth walls. These morphological features align with those of Colletotrichum spp. within the Colletotrichum gigasporum species (Liu et al. 2014). The identity of the pathogen was further confirmed through multi-locus phylogenetic analysis. The target genes including ITS, ACT, CHS-1, GAPDH, TUB2, and GS were amplified and sequenced using the primer sets ITS1/ITS4, ACT 512F/ ACT-783R, CHS-79F/ CHS-345R, GDF/GDR, T1/Bt2b, and GSF1/GSR1, respectively (Weir et al. 2012; Liu et al. 2014). The resulting sequences were deposited in GenBank (accession no: ITS: MT605261, MT605262, LC823714; ACT: MT612991, MT612992, LC823718; CHS-1: MT612993, MT612994, LC823717; GAPDH: LC811375, LC811376, LC823716; TUB2: MT612997, MT612998, LC823715; GS: LC811377, LC811378, LC823719). The constructed Bayesian and maximum likelihood tree based on combined sequences of ITS, ACT, CHS-1, GAPDH, TUB2, and GS confirmed the identification of the isolates (C01049, C01111, C01115) as C. gigasporum. Pathogenicity tests were conducted by inoculating healthy chili fruit with 70 µL of a conidial suspension (1×106 conidia /mL) of pure cultures of the isolates. The conidial suspension was applied on 10 wounded or 10 non-wounded fruit. The same number of fruit were treated with sterile distilled water as controls. Within 5 days of inoculation, symptoms consistent with anthracnose developed on the inoculated wounded fruit, whereas non-wounded and control fruit remained asymptomatic. This experiment was repeated twice. Colletotrichum gigasporum was re-isolated from diseased tissue of inoculated fruit. Colletotrichum gigasporum has been identified as the cause of anthracnose on Dalbergia odorifera, Carica papaya in China, and Brassica oleracea in India (Wan et al., 2018; Saini et al. 2022; He et al. 2023). To the best of our knowledge, this report marks the first documented instance of C. gigasporum causing anthracnose of chili pepper in South Korea. These results indicate that various species of Colletotrichum can be the fungi causing chili pepper anthracnose. The findings of this study emphasize the need for effective disease management strategies to mitigate impact of C. gigasporum on chili pepper cultivation in the region.

The implications of the early phases of human telencephalic development, involving neural stem cells (NSCs), in the etiology of cortical disorders remain elusive. Here, we explored the expression dynamics of cortical and neuropsychiatric disorder-associated genes in datasets generated from human NSCs across telencephalic fate transitions in vitro and in vivo. We identified risk genes expressed in brain organizers and sequential gene regulatory networks across corticogenesis revealing disease-specific critical phases, when NSCs are more vulnerable to gene dysfunctions, and converging signaling across multiple diseases. Moreover, we simulated the impact of risk transcription factor (TF) depletions on different neural cell types spanning the developing human neocortex and observed a spatiotemporal-dependent effect for each perturbation. Finally, single-cell transcriptomics of newly generated autism-affected patient-derived NSCs in vitro revealed recurrent alterations of TFs orchestrating brain patterning and NSC lineage commitment. This work opens new perspectives to explore human brain dysfunctions at the early phases of development., Competing Interests: COMPETING INTERESTS The authors declare no conflict of interest.

Background. The aim of the study was to synthesize liposomal nanoparticles loaded with temozolomide and ferucarbotran (LTF) and to evaluate the theranostic effect of LTF in the glioma model. Methods. We synthesized an LTF that could pass through the Blood Brain Barrier (BBB) and localize in brain tumor tissue with the help of magnet guidance. We examined the chemical characteristics. Cellular uptake and cytotoxicity studies were conducted in vitro. A biodistribution and tumor inhibition study was conduted using an in vivo glioma model. Results. The particle size and surface charge of LTF show 108 nm and -38 mV, respectively. Additionally, the presence of ferucarbotran significantly increased the contrast agent effect of glioma compared to the control group in MR imaging. Magnet-guided LTF significantly reduced the tumor size compared to control and other groups. Furthermore, compared to the control group, our results demonstrate a significant inhibition in brain tumor size and an increase in lifespan. Conclusions. These findings suggest that the LTF with magnetic guidance represents a novel approach to address current obstacles, such as BBB penetration of nanoparticles and drug resistance. Magnet-guided LTF is able to enhance therapeutic efficacy in mouse brain glioma.

The depleting supply of natural sources of rare earth elements (REE) is a concern to many nations as demand for advanced technology is becoming vital for national security. In this communication, the recovery of dysprosium(III) from aqueous systems was exemplified by a modified phosphorylated chitosan (PCs/MB) prepared by the C-Mannich reaction of phosphorylated chitosan, glutaraldehyde, and 4-hydroxycoumarin in ethanolic solution. Batch adsorption studies achieved a maximum adsorption capacity (q max ) of 34 mg/g at 25 °C and pH = 5.4 for 2 h. Fourier Transform-Infrared Spectroscopy, elemental mapping, and quantitative analyses revealed ion-exchange mechanism with C6-phosphate and a synergistic complexation with the amino group between two hexose units of the chitosan chain confirming the correlation provided by the pseudo-second order kinetics (R 2  = 0.9996), extrapolated mean free energy of adsorption (E ads ) of 12.9 kJ/mol from the corrected Dubinin-Radushkevich isotherm, and the extrapolated enthalpy of adsorption (ΔH 0 ads ) of -42.4 kJ/mol from the linearized Van't Hoff plot. Competitive adsorption with iron(II), cerium(III), and neodymium(III) demonstrated preferential removal of dysprosium(III) and complete exclusion of iron(II), which illustrates potential application in the separation of REE from electronic wastes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Unlike western countries, which have reported distinct decreases in incidence of ruptured abdominal aortic aneurysm (rAAA) over the last few decades, epidemiologic studies in Korea have not shown significant changes in incidence or mortality of rAAA. The purpose of this study was to analyze the changes in rAAA treatment outcomes and various associated risk factors over the past 2 decades., Methods: A 20-year retrospective multicenter review for rAAA cases from the period of January 2000 to December 2020 was undertaken. Preoperative, intraoperative and postoperative clinical data were extracted for patients diagnosed with rAAA. For analysis, outcomes from the early era, defined as patients treated between January 1, 2000, and December 31, 2010, were compared with outcomes from the late era, defined as patients treated between January 1, 2011, and December 31, 2020., Results: The total in-hospital mortality was 34.1% in the early era compared to 44.8% in the late era. Patients in the late era were older than those in the early era (75.2 ± 10.3 years vs. 70.3 ± 8.9 years; P = 0.009). Treatment with rAAA endovascular aneurysm repair increased from 2.3% in early to 13.8% in late era (P = 0.031). In the early era, more patients were operated by experienced surgeons than the late era (78.1% vs. 45.9%; P = 0.002). The emergency room to operating room time did not show improvement over the 20 years., Conclusions: The results indicate that mortality rate of rAAA in Korea has not changed over the last 2 decades. The study suggests the need for national preventive strategies, improved systemic coordination, and potential centralization of vascular services to enhance survival rates for rAAA., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Statins may reduce the risk of recurrent gallstone disease by decreasing bile cholesterol saturation and pathogenicity. However, limited studies have investigated this issue. This study aimed to assess whether statin doses and serum cholesterol levels were associated with a decreased risk of recurrent biliary stone diseases after the first event index, with a follow-up time of 15 years., Methods: Based on the Chang Gung Research Database (CGRD) between January 1, 2001, and December 31, 2020, we enrolled 68,384 patients with the International Classification of Diseases, Ninth and Tenth Revision codes of choledocholithiasis. After exclusions, 32,696 patients were divided into non-statin (<28 cDDD, cumulative defined daily doses) (n = 27,929) and statin (≥28 cDDD) (n = 4767) user groups for analysis. Serum cholesterol trajectories were estimated using group-based trajectory modeling (n = 8410)., Results: The statin users had higher Charlson Comorbidity Index (CCI) scores than the non-statin users. Time-dependent Cox regression analysis showed that statin use >365 cDDD was associated with a significantly lower risk of recurrent biliary stones (adjusted hazard ratio [aHR] = 0.28, 95% CI, 0.24-0.34; p < 00.0001), acute pancreatitis (aHR = 0.24, 95% CI, 0.17-0.32, p < 00.0001), and cholangitis (aHR = 0.28, 95% CI, 0.25-0.32, p < 00.0001). Cholecystectomy was also a protective factor for recurrent biliary stones (aHR = 0.41, 95% CI, 0.37-0.46; p < 00.0001). The higher trajectory serum cholesterol group (Group 3) had a lower risk trend for recurrent biliary stones (aHR = 0.79, p = 0.0700) and a lower risk of cholangitis (aHR = 0.79, p = 0.0071)., Conclusion: This study supports the potential benefits of statin use and the role of cholecystectomy in reducing the risk of recurrent biliary stone diseases., Competing Interests: Declaration of Competing Interest The authors declared that they have no conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objectives: Genetic factors are a major cause of osteoporosis. The present study evaluated the association of the apolipoprotein E (ApoE) genotype with bone mineral density (BMD) and its response to menopausal hormone therapy (MHT) in postmenopausal Korean women., Methods: This retrospective cohort study included 172 postmenopausal women with no endocrine diseases, medications, or lifestyles that would affect bone metabolism and who were continuously treated with MHT for at least 2 years. BMDs were measured at baseline and periodically., Results: Linear regression analysis demonstrated similar baseline BMDs at the lumbar spine, but significantly lower at the femur neck and total hip in the ApoE ε4 carrier than in the noncarrier group, after controlling for age, body mass index, and history of MHT usage. Overall, the Wilcoxon signed rank test demonstrated that MHT increased the BMD percentage change at all three regions, and the Generalized Estimating Equation (GEE) demonstrated significant time trends at the lumbar spine and femur neck. ApoE ε4 noncarriers exhibited a significant time trend in BMD changes at the femur neck, whereas ε4 carriers exhibited a time trend at the lumbar spine. However, BMD changes at each time point were comparable at all regions between the groups. Notably, GEE adjusted for baseline characteristics and BMD revealed a significant interaction effect of time and ApoE ε4 allele in BMD changes at the femur neck., Conclusions: Postmenopausal Korean women carrying the ApoE ε4 allele demonstrated a lower hip BMD compared with ε4 noncarriers. Furthermore, the ε4 allele may modulate hip BMD responses to MHT., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © by The Korean Society of Menopause.)

Background & Aims: Metabolomic and lipidomic analyses provide an opportunity for novel biological insights. Cholangiocarcinoma (CCA) remains a highly lethal cancer with limited response to systemic, targeted, and immunotherapeutic approaches. Using a global metabolomics and lipidomics platform, this study aimed to discover and characterize metabolomic variations and associated pathway derangements in patients with CCA., Methods: Leveraging a biospecimen collection, including samples from patients with digestive diseases and normal controls, global serum metabolomic and lipidomic profiling was performed on 213 patients with CCA and 98 healthy controls. The CCA cohort of patients included representation of intrahepatic, perihilar, and distal CCA tumours. Metabolome-wide association studies utilizing multivariable linear regression were used to perform case-control comparisons, followed by pathway enrichment analysis, CCA subtype analysis, and disease stage analysis. The impact of biliary obstruction was evaluated by repeating analyses in subsets of patients only with normal bilirubin levels., Results: Of the 420 metabolites that discriminated patients with CCA from controls, decreased abundance of cysteine-glutathione disulfide was most closely associated with CCA. Additional conjugated bile acid species were found in increased abundance even in the absence of clinically relevant biliary obstruction denoted by elevated serum bilirubin levels. Pathway enrichment analysis also revealed alterations in caffeine metabolism and mitochondrial redox-associated pathways in the serum of patients with CCA., Conclusions: The presented metabolomic and lipidomic profiling demonstrated multiple alterations in the serum of patients with CCA. These exploratory data highlight novel metabolic pathways in CCA and support future work in therapeutic targeting of these pathways and the development of a precision biomarker panel for diagnosis., Impact and Implications: Cholangiocarcinoma (CCA) is a highly lethal hepatobiliary cancer with limited treatment response, highlighting the need for a better understanding of the disease biology. Using a global metabolomics and lipidomics platform, we characterized distinct changes in the serum of 213 patients with CCA compared with healthy controls. The results of this study elucidate novel metabolic pathways in CCA. These findings benefit stakeholders in both the clinical and research realms by providing a foundation for improved disease diagnostics and identifying novel targets for therapeutic design., Competing Interests: The authors have no relevant conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2024 The Author(s).)

Alzheimer's disease (AD) is a progressive disease leading to cognitive decline, and to prevent it, researchers seek to diagnose mild cognitive impairment (MCI) early. Particularly, non-amnestic MCI (naMCI) is often mistaken for normal aging as the representative symptom of AD, memory decline, is absent. Subjective cognitive decline (SCD), an intermediate step between normal aging and MCI, is crucial for prediction or early detection of MCI, which determines the presence of AD spectrum pathology. We developed a computer-based cognitive task to classify the presence or absence of AD pathology and stage within the AD spectrum, and attempted to perform multi-stage classification through electroencephalography (EEG) during resting and memory encoding state. The resting and memory-encoding states of 58 patients (20 with SCD, 10 with naMCI, 18 with aMCI, and 10 with AD) were measured and classified into four groups. We extracted features that could reflect the phase, spectral, and temporal characteristics of the resting and memory-encoding states. For the classification, we compared nine machine learning models and three deep learning models using Leave-one-subject-out strategy. Significant correlations were found between the existing neurophysiological test scores and performance of our computer-based cognitive task for all cognitive domains. In all models used, the memory-encoding states realized a higher classification performance than resting states. The best model for the 4-class classification was cKNN. The highest accuracy using resting state data was 67.24%, while it was 93.10% using memory encoding state data. This study involving participants with SCD, naMCI, aMCI, and AD focused on early Alzheimer's diagnosis. The research used EEG data during resting and memory encoding states to classify these groups, demonstrating the significance of cognitive process-related brain waves for diagnosis. The computer-based cognitive task introduced in the study offers a time-efficient alternative to traditional neuropsychological tests, showing a strong correlation with their results and serving as a valuable tool to assess cognitive impairment with reduced bias., (© 2024. The Author(s).)

Implant failures have been associated with a diversity of etiologic processes, predominately arising from bone loss (peri-implantitis) due to inadequate maintenance of oral hygiene or excess luting agents. The aim of this article is to report a novel case of the apparent failure of a dental implant to undergo osseointegration in the presence of submerged pencil graphite. Practitioners are advised to carefully evaluate the clinical and radiographic site of a proposed implant for occult foreign substances. Embedded pencil graphite in the jawbone may promote a foreign body reaction and should be considered in the list of possible contributing factors to dental implant complications., Competing Interests: No conflicts of interest reported.

⨯ Graptoveria 'Silver Star' (a cross between Graptopetalum filiferum and Echeveria agavoides ) from the Crassulaceae family, are an evergreen succulent with lotus constellation-shaped flowers, making it consumer favorite ornamental plant in Korea. In 2019, Korea's ornamental production was estimated at KRW 517.4 billion (EUR 382 million), from 4,244 ha of farming area according to the Ministry of Agriculture, Food and Rural Affairs of Korea. In July 2023, ⨯ Graptoveria 'Silver Star' plants with chlorotic leaves, root and collar rot were observed in a greenhouse in Yongin (37°14'27.9"N, 127°10'39.19"E), Korea. To isolate the causal agent, small pieces (1 mm 2 ) of symptomatic tissues were surface-sterilized using 1% NaOCl for 1 min, then put onto a water agar (WA) plate and incubated in the dark at 25℃ for five days. Two isolates (FD00202, FD00203) were obtained from diseased leaves, stem and roots by isolating single sporangium. To investigate the morphological characteristics of the isolates, the mycelium from potato dextrose agar (PDA) were transferred to V8 agar (V8A) followed by incubation at 25°C in the dark for 7 days. The isolates produced dense cottony mycelium, with slightly petaloid and light rossette pattern, with coralloid edges measuring 70 to 83 mm diameter. Sporangium were spheroid (30.0-48.0 µm long, 25.0-35.0 µm wide) with globose chlamydospores (17.0-50.0 µm long, 18.0-38.0 µm wide). Oogonia were not observed. Morphological and cultural characteristics of these isolates were phenotypically similar to that of Phytophthora nicotianae (Faedda et al. 2013; Abad et al. 2023). For molecular identification, genomic DNA was extracted from 5 days old cultures using the Maxwell ® RSC PureFood GMO and Authentication Kit (Promega). Two gene regions, the rDNA-ITS, COX I were amplified and sequenced using primers ITS1/ITS4 and FM83/FM84, respectively (White et al. 1990; Martin and Tooley 2003). The resulting sequences were deposited in GenBank with accession no. LC783858 to LC783861. A BLASTn search of the DNA sequences from ITS, COX I showed 99.81 and 98.94% identity to P. nicotianae isolate IMI 398853, respectively. Maximum likelihood phylogenetic analyses were performed for the combined data set with ITS, COX I using MEGA7 under the Tamura-Nei model (Kumar et al. 2016). The isolates formed a monophyletic group with P. nicotianae isolate IMI 398853, CPHST BL162, and CPHST BL 44. Based on morphological characteristics and molecular analysis, the isolates were identified as P. nicotianae . T confirm their pathogenicity, inoculum was prepared in accordance with Ann (2000). Artificially wounded healthy plant roots were dipped in zoospore suspension (3.0 × 10 6 zoospore/ml) for 24 hours, with mock-treated plants (control) dipped in sterile distilled water (Ann. 2000). Thereafter, the plants were transplanted into new medium and kept under high humidity. Symptoms were observed after 10 days of incubation. The plants inoculated with P. nicotianae showed similar symptoms of chlorotic leaves with root and collar rot, while control remained symptomless. The pathogen was re-isolated from all inoculated plants and confirmed as P. nicotianae by morphological and molecular analysis. but not from controls, fulfilling Koch's postulates. Phytophthora nicotianae was previously report on Echeveria derenbergii and Kalanchoe blossfeldiana causing brown spot on stems and roots in California and Korea, respectively (French 1989; Oh and Son 2008). To best of our knowledge, this is the first report of P. nicotianae causing root and collar rot on ⨯ Graptoveria 'Silver Star' plants in the Korea.

Luteoviruses (family Tombusviridae ) and poleroviruses (family Solemoviridae ) are economically important pathogens of cereals such as wheat ( Triticum aestivum ), barley ( Hordeum vulgare ) and oat ( Avena sativa ). In Australia, the luteoviruses barley yellow dwarf virus PAV (BYDV PAV) and barley yellow dwarf virus MAV (BYDV MAV), along with the poleroviruses cereal yellow dwarf virus RPV (CYDV RPV) and maize yellow dwarf virus RMV (MYDV RMV), were distinguished from each other and reported in the 1980s (Sward and Lister 1988; Waterhouse and Helms 1985). The poleroviruses barley virus G (BVG) and cereal yellow dwarf virus RPS (CYDV RPS) were reported in Australia more recently (Nancarrow et al. 2019; Nancarrow et al. 2023), while the luteovirus barley yellow dwarf virus PAS (BYDV PAS) has not previously been reported in Australia. During 2010, an oat plant exhibiting yellow/ red leaf discoloration and stunted growth was collected from a roadside in Horsham, Victoria, Australia. The plant tested positive for BYDV PAV and negative for BYDV MAV, CYDV RPV and MYDV RMV by tissue blot immunoassay (TBIA) as described by Trębicki et al (2017). The virus isolate has since been continuously maintained in a glasshouse in live wheat plants using aphids ( Rhopalosiphum padi ). In 2021, total RNA extracted from a wheat plant infected with this isolate (Nancarrow et al. 2023) tested positive for BYDV PAV by RT-PCR using the primers BYDV-1/BYDV-2 (Rastgou et al. 2005), but negative for BYDV PAV, CYDV RPV and MYDV RMV using other published primers (Deb and Anderson 2008). A high-throughput sequencing (HTS) library was prepared from the total RNA with the NEBNext Ultra II RNA Library Prep Kit for Illumina (NEB) without ribosomal RNA depletion and sequenced on a NovaSeq 6000 (Illumina). Raw reads were trimmed and filtered using fastp v0.20.0 (Chen et al. 2018) while de novo assembly of all of the resulting 5,049,052 reads was done using SPAdes v3.15.3 (Nurk et al. 2017). BLASTn analysis of the resulting 4,067 contigs (128- 12,457 bp in length) revealed only one large virus-like contig (5,649 bp) which was most similar to BYDV PAS isolates on NCBI GenBank, sharing 87% nucleotide (nt) identity with BYDV PAS isolate OH2 (MN128939), 86% nt identity with the BYDV PAS reference sequence (NC&#95;002160) and 82% nt identity with the BYDV PAV reference sequence (NC&#95;004750). Additionally, 4,008 HTS reads were mapped to the assembled genome sequence with Bowtie2 v2.4.5. (Langmead and Salzberg 2012) with 100% genome coverage and an average coverage depth of 101X. Primers were designed to the assembled genome sequence to generate overlapping amplicons across the genome, and the resulting amplicons were Sanger sequenced. This confirmed the genome sequence of BYDV PAS isolate PT from Australia (5649 bp, GC content 47.9%), which was deposited in GenBank (LC782749). Ten additional plant samples collected from western Victoria, Australia, all tested positive for BYDV PAS by RT-PCR using the primers PASF and PASR (Laney et al. 2018). The additional samples consisted of one oat sample collected in 2005, one barley sample collected in 2007, three wheat samples collected in 2016 and one barley, one brome grass ( Bromus sp.) and three wheat samples collected in 2020. BYDV PAS is also efficiently transmitted by R. padi but is often more prevalent and severe than BYDV PAV; it can also overcome some sources of virus resistance that are effective against BYDV PAV (Chay et al. 1996, Robertson and French 2007). To our knowledge, this is the first report of BYDV PAS in Australia. Further work is needed to determine the extent of its distribution, incidence, impacts and epidemiology in Australia, along with its relationship to other BYDV PAS isolates.

Background: Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia-dysplasia-carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer., Case Presentation: A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia-dysplasia-carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor., Conclusions: Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia-dysplasia-carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca., (© 2024. The Author(s).)

Advanced molecular and cellular technologies provide promising tools for wildlife and biodiversity conservation. Induced pluripotent stem cell (iPSC) technology offers an easily accessible and infinite source of pluripotent stem cells, and have been derived from many threatened wildlife species. This paper describes the first successful integration-free reprogramming of adult somatic cells to iPSCs, and their differentiation, from three endangered Southeast Asian primates: the Celebes Crested Macaque (Macaca nigra), the Lar Gibbon (Hylobates lar), and the Siamang (Symphalangus syndactylus). iPSCs were also generated from the Proboscis Monkey (Nasalis larvatus). Differences in mechanisms could elicit new discoveries regarding primate evolution and development. iPSCs from endangered species provides a safety net in conservation efforts and allows for sustainable sampling for research and conservation, all while providing a platform for the development of further in vitro models of disease., (© 2024. The Author(s).)

Friend Leukemia Virus Integration 1 (FLI-1) is a member of E26 transformation-specific family of transcription factors that participates in hematopoietic and vascular endothelial cell development. Immunohistochemical detection of FLI-1 has been widely used to diagnose vascular tumors or, more evidently, Ewing's sarcoma. However, the expression pattern of FLI-1 in hematolymphoid neoplasms remains unclear. Therefore, in this study, we aimed to investigate the expression of FLI-1 in these tumors, focusing on high-grade lesions, which presents a diagnostic challenge by mimicking Ewing's sarcoma. We evaluated the expression FLI-1 in various types of lymphoid and plasmacytic tumors, including 27 plasmablastic lymphomas, 229 diffuse large B-cell lymphomas, 22 precursor T- or B-lymphoblastic lymphomas, 24 angioimmunoblastic-type nodal T-follicular helper cell lymphomas, 52 peripheral T-cell lymphomas, NOS, 18 Burkitt lymphomas, 18 non-gastric lymphomas of mucosa-associated lymphoid tissue, 38 chronic lymphocytic leukemia/small lymphocytic lymphomas, 15 mantle cell lymphomas, 23 gastric MALT lymphomas, 50 plasma cell myelomas, and 38 follicular lymphomas. We calculated the H-scores of FLI-1 immunostaining, ranging from 0 to 200, and used the scores to analyze the clinicopathological significance of FLI-1 statistically. FLI-1 was expressed to varying degrees in all types of hematological tumors. FLI-1 expression was detected in 84.1% of patients (466/554). FLI-1 was highly expressed in precursor T- or B-lymphoblastic lymphomas. Follicular lymphomas exhibited low FLI-1 expression. In plasmablastic lymphoma, 85.2% of the patients were focally positive for FLI-1. FLI-1 expression did not correlate with clinicopathological variables, such as demographic data or disease stage, in patients with plasmablastic lymphoma and diffuse large B-cell lymphoma. However, FLI-1 overexpression was associated with poorer overall survival in patients with plasmablastic lymphoma. This study demonstrates that FLI-1 is expressed in various hematolymphoid neoplasms. FLI-1 expression can lead to diagnostic confusion, especially in small blue round cell tumors, such as lymphoblastic lymphoma, plasmablastic lymphoma, and plasma cell myeloma, when distinguishing tumors positive for CD99 and CD56 without CD3, CD20, or CD45. Our findings also suggested the possibility of FLI-1 as a potential prognostic biomarker for plasmablastic lymphoma., (© 2024. The Author(s).)

The impacts of precipitation change on forest carbon (C) storage will have global consequences, as forests play a major role in sequestering anthropogenic CO 2 . Although forest soils are one of the largest terrestrial C pools, there is great uncertainty around the response of forest soil organic carbon (SOC) to precipitation change, which limits our ability to predict future forest C storage. To address this, we conducted a meta-analysis to determine the effect of drought and irrigation experiments on SOC pools, plant C inputs and the soil environment based on 161 studies across 139 forest sites worldwide. Overall, forest SOC content was not affected by precipitation change, but both drought and irrigation altered plant C inputs and soil properties associated with SOC formation and storage. Drought may enhance SOC stability by altering soil aggregate fractions, but the effect of irrigation on SOC fractions remains unexplored. The apparent insensitivity of SOC to precipitation change can be explained by the short duration of most experiments and by biome-specific responses of C inputs and pools to drought or irrigation. Importantly, we demonstrate that SOC content is more likely to decline under irrigation at drier temperate sites, but that dry forests are currently underrepresented across experimental studies. Thus, our meta-analysis advances research into the impacts of precipitation change in forests by revealing important differences among forest biomes, which are likely linked to plant adaptation to extant conditions. We further demonstrate important knowledge gaps around how precipitation change will affect SOC stability, as too few studies currently consider distinct soil C pools. To accurately predict future SOC storage in forests, there is an urgent need for coordinated studies of different soil C pools and fractions across existing sites, as well as new experiments in underrepresented forest types., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The heterogeneity of depressive and anxiety disorders complicates clinical management as it may account for differences in trajectory and treatment response. Self-schemas, which can be determined by Self-Referential Judgements (SRJs), are heterogeneous yet stable. SRJs have been used to characterize personality in the general population and shown to be prognostic in depressive and anxiety disorders., Methods: In this study, we used SRJs from a Self-Referential Encoding Task (SRET) to identify clusters from a clinical sample of 119 patients recruited from the Institute of Mental Health presenting with depressive or anxiety symptoms and a non-clinical sample of 115 healthy adults. The generated clusters were examined in terms of most endorsed words, cross-sample correspondence, association with depressive symptoms and the Depressive Experiences Questionnaire and diagnostic category., Results: We identify a 5-cluster solution in each sample and a 7-cluster solution in the combined sample. When perturbed, metrics such as optimum cluster number, criterion value, likelihood, DBI and CHI remained stable and cluster centers appeared stable when using BIC or ICL as criteria. Top endorsed words in clusters were meaningful across theoretical frameworks from personality, psychodynamic concepts of relatedness and self-definition, and valence in self-referential processing. The clinical clusters were labeled "Neurotic" (C1), "Extraverted" (C2), "Anxious to please" (C3), "Self-critical" (C4), "Conscientious" (C5). The non-clinical clusters were labeled "Self-confident" (N1), "Low endorsement" (N2), "Non-neurotic" (N3), "Neurotic" (N4), "High endorsement" (N5). The combined clusters were labeled "Self-confident" (NC1), "Externalising" (NC2), "Neurotic" (NC3), "Secure" (NC4), "Low endorsement" (NC5), "High endorsement" (NC6), "Self-critical" (NC7). Cluster differences were observed in endorsement of positive and negative words, latency biases, recall biases, depressive symptoms, frequency of depressive disorders and self-criticism., Discussion: Overall, clusters endorsing more negative words tended to endorse fewer positive words, showed more negative biases in reaction time and negative recall bias, reported more severe depressive symptoms and a higher frequency of depressive disorders and more self-criticism in the clinical population. SRJ-based clustering represents a novel transdiagnostic framework for subgrouping patients with depressive and anxiety symptoms that may support the future translation of the science of self-referential processing, personality and psychodynamic concepts of self-definition to clinical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tan, Wang, Tan, Ong, Ooi, Lee, Rane, Tey, Chua, Goh, Lam, Chakraborty, Yew, Ong, Kee, Lim, Hashim, Lu, Meany, Tolomeo, Lee, Tan and Keppo.)

Our study retrospectively investigated differential patterns of the functional connectivity (FC) of core brain regions synchronous with morphometric changes associated with sexual dysfunction in menopausal women, and their correlations with sexual hormones. Twenty-three premenopausal women (mean age: 41.52 ± 7.38 years) and 21 menopausal women (mean age: 55.52 ± 2.80 years) underwent sex hormone level measurements with high-resolution T1 and functional magnetic resonance imaging (MRI) during rest, neutral, and sexual arousal conditions. Analysis of covariance adjusted for age was used to compare the FC and gray matter (GM) volume between the two groups. Menopausal women showed lower GM volumes in the superior frontal gyrus (SFG), superior temporal pole, parahippocampal gyrus (PHG), hippocampus (Hip), amygdala (Amg), and cerebellum (Cb) compared to premenopausal women ( p < 0.05). In addition, compared to premenopausal women, menopausal women showed decreased FC of seed regions involved in the SFG, frontal eye fields, and Amg, as well as target regions involved in the PHG, Hip, inferior frontal gyrus, Cb, and vermis ( p < 0.005). Furthermore, the FC between the right Amg and right Cb and between the left Amg and right Cb during sexual arousal in both groups was positively correlated with total estrogen and estradiol levels, respectively ( p < 0.01). The GM volume values in the right Amg and right Cb were positively correlated with total estrogen and estradiol levels ( p < 0.05). Our study demonstrated an association between menopause-related differential FC and GM volume variations and fluctuating sex hormones. Our findings highlight that overlapping brain regions with functional alterations and morphometric changes are closely linked with menopausal symptom-related decreases in sexual arousal and hormone levels.

Narrow-head ragwort ( Ligularia stenocephala (Maxim.) Matsum. & Koidz.) has been used for medicinal purposes and a leafy vegetable in South Korea (Choi et al., 2007; Debnath et al., 2017). In May 2022, brown spots and blight were observed on the leaves in a farmer's field in Namwon (35°26'58.9"N, 127°28'55.9"E), Korea. About 80% of the plants in a 3000 m2 cultivation area were infected. To isolate the causal agent, small pieces (1 mm 2 ) surface-sterilized (1% NaOCl for 1 min) symptomatic leaf tissues were put onto a water agar (WA) plate and incubated in the dark at 25℃. After five days of incubation, two isolates (FD00021, FD00022) were obtained from diseased leaves using a single spore isolation technique. Morphological characteristics were examined after seven days of incubation at 25℃ in the dark. Colonies were 51.6 to 65.3 mm in diameter, gray-green in the center, and ivory at the edge. Conidiophores were straight or curved and 10 - 34 × 4 - 5 μm. Conidia were solitary or two to four in a chain, long ellipsoid to obclavate, one to thirteen transverse septa, 52 - 169 ×14 - 34 μm, blunt-tapered beak variable in size 4 - 56 × 3 - 10 μm (n=75). The morphological and cultural characteristics of the isolates were consistent with that of Alternaria cinerariae (Nishikawa and Nakashima, 2015; Simmons, 2007). For molecular identification, genomic DNA was extracted from 5-day-old cultures using the Maxwell ® RSC PureFood GMO and Authentication Kit (Promega). Five gene regions, including rDNA ITS, GPD, Alt a, RPB2, and EF1-α were amplified and sequenced using ITS1/ITS4, gpd1/gpd2, Alt-a1-for/ Alt-a1-rev, RPB2-5F2/RPB2-7cR, and EF1-728F/EF1-986R primer sets respectively (Wang et al., 2022; Garibaldi et al., 2022). The resulting sequences were deposited in GenBank with accession no. OP785152, OP785153 and OP832000 to OP832007). The concatenated genes (rDNA ITS, GPD, Alt a, RPB2, and EF1-α) sequence identity of the FD00021 and FD00022 against the reference strain A. cinerariae CBS 116495 is 99.92% (2572/2574) and 99.84% (2570/2574), respectively. Maximum Likelihood tree was inferred based on the concatenated sequences of the five gene regions using the Kimura 2-parameter model with 1,000 bootstrap replications. The phylogenetic tree showed that the present strains and A. cinerariae CBS 116495 fell into the same clade with high bootstrap support (100%). Based on morphological characteristics and molecular analysis, the isolates were identified as A. cinerariae. To confirm their pathogenicity, drops (70 μl) of conidial suspension (1×10 4 spores/ml) were applied on intact healthy leaves (3 leaves/plant) of plants (3 plants/isolate) that had been cultivated for one month after transplantation as seedlings. Controls were treated with sterile distilled water. The treated plants were covered with plastic boxes to maintain humidity around 90% and were maintained in an incubator at 25℃ in a 12-hour light-dark cycle. Symptoms appeared only on inoculated leaves after four days of inoculation, while controls remained asymptomatic. The A. cinerariae isolates were re-isolated from infected tissue of the inoculated leaves, thus fulfilling Koch's postulates. Alternaria cinerariae is an important plant pathogen that can cause leaf spot and blight on a variety of host plants including Cineraria spp. and Tussilago farfara (He et al. 2020). This is the first report on leaf spot on Narrow-head ragwort caused by A. cinerariae in the world. Leaf spot disease caused by Alternaria cinerariae is a significant threat to narrow-head ragwort agriculture in South Korea. Therefore, its control strategies are necessary for increasing productivity.

Hybrid therapy is a recommended first-line anti- H. pylori treatment option in the American College of Gastroenterology guidelines, the Bangkok Consensus Report on H. pylori management, and the Taiwan H. pylori Consensus Report. However, the cure rates of eradication therapy in some countries are suboptimal, and the factors affecting the treatment efficacy of hybrid therapy remain unclear. The aim of this study is to identify the independent risk factors predicting eradication failure of hybrid therapy in the first-line treatment of H. pylori infection. A retrospective cohort study was conducted on 589 H. pylori -infected patients who received 14-day hybrid therapy between September 2008 and December 2021 in ten hospitals in Taiwan. The patients received a hybrid therapy containing a dual regimen with a proton pump inhibitor (PPI) plus amoxicillin for an initial 7 days and a quadruple regimen with a PPI plus amoxicillin, metronidazole and clarithromycin for a final 7 days. Post-treatment H. pylori status was assessed at least 4 weeks after completion of treatment. The relationships between eradication rate and 13 host and bacterial factors were investigated via univariate and multivariate analyses. In total, 589 patients infected with H. pylori infection were included in the study. The eradication rates of hybrid therapy were determined as 93.0% (95% confidence interval (CI): 90.9-95.1%), 94.4% (95% CI: 93.8-97.2%) and 95.5%% (95% CI: 93.8-97.2%) by intention-to-treat, modified intention-to-treat and per-protocol analyses, respectively. Univariate analysis showed that the eradication rate of clarithromycin-resistant strains was lower than that of clarithromcyin-susceptible strains (83.3% (45/54) vs. 97.6%% (280/287); p < 0.001). Subjects with poor drug adherence had a lower cure rate than those with good adherence (73.3% (11/15) vs. 95.5% (534/559); p = 0.005). Other factors such as smoking, alcohol drinking, coffee consumption, tea consumption and type of PPI were not significantly associated with cure rate. Multivariate analysis revealed that clarithromcyin resistance of H. pylori and poor drug adherence were independent risk factors related to eradication failure of hybrid therapy with odds ratios of 4.8 (95% CI: 1.5 to 16.1; p = 0.009) and 8.2 (95% CI: 1.5 to 43.5; p = 0.013), respectively. A 14-day hybrid therapy has a high eradication rate for H. pylori infection in Taiwan, while clarithromycin resistance of H. pylori and poor drug adherence are independent risk factors predicting eradication failure of hybrid therapy.

To investigate the incidence and impact of superior cerebellar artery (SCA) occlusion remaining after thrombectomy for acute basilar artery occlusion (BAO). We retrospectively analyzed data from 116 patients who underwent thrombectomy for BAO. The patency of SCA was assessed on final angiograms. Clinical and radiologic data of the patients were retrieved from a prospectively collected database and analyzed. All patients underwent pretreatment and follow-up DWI to detect new infarctions in SCA territory. Ten patients (8.6%) had SCA occlusions on final angiograms. Of these, two patients had bilateral occlusions. A new infarction with a diameter ranged from 4 to 11 mm in corresponding SCA territory occurred in 5 of 10 patients. No patients with SCA occlusions experienced symptomatic cerebellar hemorrhage or malignant cerebellar infarction. Nine of 12 SCA occlusions showed spontaneous recanalization on follow-up CT angiography. Four of 10 patients showed 90-day favorable outcome (mRS 0-3) and 90-day mortality occurred in one patient. SCA occlusions remaining after thrombectomy for acute BAO had a benign clinical course. Most of these lesions recanalized spontaneously. Our study suggests that attempts to recanalize remnant SCA occlusion may be unnecessary after basilar artery thrombectomy., (© 2023. The Author(s).)