ABSTRACT
Electric vehicles (EVs) are imposing ever-challenging standards on the lifetime and safety of lithium-ion batteries (LIBs); consequently, real-time nondestructive monitoring of battery cell degradation is highly desired. Unfortunately, high-nickel (Ni) layered oxides, the preferred LIB cathodes for EVs, undergo performance degradation originating from microcrack formation during cycling. Entropymetry is introduced as a real-time analytic tool for monitoring the evolution of microcracks in these cathodes along the state of charge. The entropy change of the layered cathode is associated with the lattice configuration and reflects the structural heterogeneity relevant to the evolution of these microcracks. The structural heterogeneity was correlated with peak broadening in in-situ X-ray diffractometry while varying the experimental conditions that affect crack formation such as the upper cutoff voltage during charging and the Ni-content of the active material. Entropymetry, proposed here as a nondestructive diagnostic tool, can contribute greatly to the safe and reliable operation of LIBs for EVs.
ABSTRACT
The minimally invasive deployment of scaffolds is a key safety factor for the regeneration of cartilage and bone defects. Osteogenesis relies primarily on cell-matrix interactions, whereas chondrogenesis relies on cell-cell aggregation. Bone matrix expansion requires osteoconductive scaffold degradation. However, chondrogenic cell aggregation is promoted on the repellent scaffold surface, and minimal scaffold degradation supports the avascular nature of cartilage regeneration. Here, a material satisfying these requirements for osteochondral regeneration is developed by integrating osteoconductive hydroxyapatite (HAp) with a chondroconductive shape memory polymer (SMP). The shape memory function-derived fixity and recovery of the scaffold enabled minimally invasive deployment and expansion to fill irregular defects. The crystalline phases on the SMP surface inhibited cell aggregation by suppressing water penetration and subsequent protein adsorption. However, HAp conjugation SMP (H-SMP) enhanced surface roughness and consequent cell-matrix interactions by limiting cell aggregation using crystal peaks. After mouse subcutaneous implantation, hydrolytic H-SMP accelerated scaffold degradation compared to that by the minimal degradation observed for SMP alone for two months. H-SMP and SMP are found to promote osteogenesis and chondrogenesis, respectively, in vitro and in vivo, including the regeneration of rat osteochondral defects using the binary scaffold form, suggesting that this material is promising for osteochondral regeneration.
ABSTRACT
BACKGROUND AND PURPOSE: The etiological distribution of oculomotor nerve palsy has varied amongst the studies. This study aimed to define the clinical features and underlying etiologies of isolated oculomotor nerve palsy by recruiting patients from all departments in a referral-based university hospital. METHODS: The medical records of 672 patients who had a confirmed diagnosis of isolated oculomotor nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, South Korea, from 2003 to 2020 were reviewed. A proportion of the etiology of isolated oculomotor nerve palsy was also compared with that of patients pooled from the previous studies that were searched on PubMed in May 2022. RESULTS: The most common etiology was microvascular (n = 168, 26.5%), followed by vascular anomalies (n = 110, 17.4%), neoplastic (n = 86, 13.6%), inflammatory (n = 79, 12.5%), idiopathic (n = 60, 9.5%) and traumatic (n = 53, 8.4%). Neurologists were mainly involved in the management of microvascular and inflammatory oculomotor nerve palsies whilst ophthalmologists mainly participated in the care of idiopathic, neoplastic and traumatic palsies. Neurosurgeons mostly took care of oculomotor nerve palsy due to vascular anomalies. CONCLUSIONS: The proportion of etiologies of isolated oculomotor nerve palsy may differ according to the specialties involved in the management. The results of previous studies on the etiological distribution of isolated oculomotor nerve palsy should be interpreted with this consideration.
Subject(s)
Oculomotor Nerve Diseases , Humans , Oculomotor Nerve Diseases/etiology , Oculomotor Nerve Diseases/epidemiology , Middle Aged , Adult , Male , Female , Aged , Adolescent , Young Adult , Child , Aged, 80 and over , Child, Preschool , Republic of Korea/epidemiologyABSTRACT
BACKGROUND AND PURPOSE: The etiologies of abducens nerve palsy have shown a large variability among studies. This study aimed to establish the clinical features and underlying etiologies of isolated abducens nerve palsy by recruiting patients from all departments in a referral-based university hospital. METHODS: We reviewed the medical records of 807 patients with a confirmed diagnosis of isolated abducens nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, Republic of Korea, from 2003 to 2020. We also compared the proportion of etiology with that of the patients pooled from the previous studies. RESULTS: The most common etiology was microvascular (n = 296, 36.7%), followed by idiopathic (n = 143, 17.7%), neoplastic (n = 115, 14.3%), vascular anomalies (n = 82, 10.2%), inflammatory (n = 76, 9.4%), and traumatic (n = 35, 4.3%). Patients were mostly managed by ophthalmologists (n = 576, 71.4%), followed by neurologists (n = 479, 59.4%), emergency physicians (n = 278, 34.4%), neurosurgeons (n = 191, 23.7%), and others (n = 72, 8.9%). The proportion of etiology significantly differed according to the age and sex of the patients and the specialties involved in the management (p < 0.001). Compared to the pooled data from the previous reports, the current study showed a higher prevalence of microvascular cause but a lower occurrence of traumatic and neoplastic causes. CONCLUSIONS: The results of previous studies on etiologic distribution of isolated abducens nerve palsy should be interpreted with consideration of the demographic features of patients recruited and the specialties involved.
Subject(s)
Abducens Nerve Diseases , Humans , Abducens Nerve Diseases/epidemiology , Abducens Nerve Diseases/etiology , Abducens Nerve Diseases/diagnosis , Causality , Republic of Korea/epidemiology , NeurologistsABSTRACT
Histone modification and DNA methylation are associated with varying epigenetic "landscapes," but detailed mechanistic and functional links between the two remain unclear. Using the ATRX-DNMT3-DNMT3L (ADD) domain of the DNA methyltransferase Dnmt3a as a paradigm, we apply protein engineering to dissect the molecular interactions underlying the recruitment of this enzyme to specific regions of chromatin in mouse embryonic stem cells (ESCs). By rendering the ADD domain insensitive to histone modification, specifically H3K4 methylation or H3T3 phosphorylation, we demonstrate the consequence of dysregulated Dnmt3a binding and activity. Targeting of a Dnmt3a mutant to H3K4me3 promoters decreases gene expression in a subset of developmental genes and alters ESC differentiation, whereas aberrant binding of another mutant to H3T3ph during mitosis promotes chromosome instability. Our studies support the general view that histone modification "reading" and DNA methylation are closely coupled in mammalian cells, and suggest an avenue for the functional assessment of chromatin-associated proteins.
Subject(s)
DNA (Cytosine-5-)-Methyltransferases/genetics , Embryonic Stem Cells/cytology , Histones/genetics , Protein Engineering , Animals , Cell Differentiation , DNA Helicases/genetics , DNA Methylation , DNA Methyltransferase 3A , Mice , Mice, Inbred C57BL , Mitosis/genetics , Nuclear Proteins/genetics , Phosphorylation , Promoter Regions, Genetic , Protein Structure, Tertiary , X-linked Nuclear ProteinABSTRACT
BACKGROUND & AIMS: Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the predominant liver cancers in children, though their respective treatment options and associated outcomes differ dramatically. Risk stratification using a combination of clinical, histological, and molecular parameters can improve treatment selection, but it is particularly challenging for tumors with mixed histological features, including those in the recently created hepatocellular neoplasm not otherwise specified (HCN NOS) provisional category. We aimed to perform the first molecular characterization of clinically annotated cases of HCN NOS. METHODS: We tested whether these histological features are associated with genetic alterations, cancer gene dysregulation, and outcomes. Namely, we compared the molecular features of HCN NOS, including copy number alterations, mutations, and gene expression profiles, with those in other pediatric hepatocellular neoplasms, including HBs and HCCs, as well as HBs demonstrating focal atypia or pleomorphism (HB FPAs), and HBs diagnosed in older children (>8). RESULTS: Molecular profiles of HCN NOS and HB FPAs revealed common underlying biological features that were previously observed in HCCs. Consequently, we designated these tumor types collectively as HBs with HCC features (HBCs). These tumors were associated with high mutation rates (â¼3 somatic mutations/Mb) and were enriched with mutations and alterations in key cancer genes and pathways. In addition, recurrent large-scale chromosomal gains, including gains of chromosomal arms 2q (80%), 6p (70%), and 20p (70%), were observed. Overall, HBCs were associated with poor clinical outcomes. CONCLUSIONS: Our study indicates that histological features seen in HBCs are associated with combined molecular features of HB and HCC, that HBCs are associated with poor outcomes irrespective of patient age, and that transplanted patients are more likely to have good outcomes than those treated with chemotherapy and surgery alone. These findings highlight the importance of molecular testing and early therapeutic intervention for aggressive childhood hepatocellular neoplasms. LAY SUMMARY: We molecularly characterized a class of histologically aggressive childhood liver cancers and showed that these tumors are clinically aggressive and that their observed histological features are associated with underlying recurrent molecular features. We proposed a diagnostic algorithm to identify these cancers using a combination of histological and molecular features, and our analysis suggested that these cancers may benefit from specialized treatment strategies that may differ from treatment guidelines for other childhood liver cancers.
Subject(s)
Carcinoma, Hepatocellular , Hepatoblastoma , Liver Neoplasms , Carcinoma, Hepatocellular/pathology , Child , Chromosome Aberrations , Hepatoblastoma/metabolism , Humans , Liver Neoplasms/pathology , Mutation , Young AdultABSTRACT
BACKGROUND AND PURPOSE: Trochlear palsy is the most common cause of vertical diplopia. The etiologies of trochlear palsy have shown a large discrepancy among studies. This study aimed to establish the clinical features and underlying etiologies of isolated trochlear palsy by recruiting the patients from all departments in a referral-based university hospital. METHODS: We reviewed the medical records of 1258 patients who had a confirmed diagnosis of isolated trochlear palsy at all departments of Seoul National University Bundang Hospital, Seongnam, South Korea, from 2003 to 2020. We also compared the proportion of etiologies with that of the patients pooled from previous studies. RESULTS: The most common etiology was congenital (n = 330, 32.4%), followed by idiopathic (n = 256, 25.1%), microvascular (n = 212, 20.8%), and traumatic (n = 145, 14.2%). These four etiologies explained 92.5% of isolated trochlear palsy. Patients were mostly managed by ophthalmologists (n = 841, 82.5%), followed by neurologists (n = 380, 37.3%), emergency physicians (n = 197, 19.3%), neurosurgeons (n = 75, 7.4%), and others (n = 18, 1.8%). The etiologic distribution of isolated trochlear palsy in the current study did not differ from that of 2664 patients pooled from the previous studies. CONCLUSIONS: The proportion of etiologies of isolated trochlear palsy differs according to the age ranges of the patients and specialties involved in the management. The etiologic distribution of isolated trochlear palsy in the current study was comparable to the pooled result of previous reports.
Subject(s)
Diplopia , Paralysis , Humans , Diplopia/complications , Diplopia/diagnosis , Paralysis/etiology , Republic of KoreaABSTRACT
We introduce a method for simultaneous prediction of microRNA-target interactions and their mediated competitive endogenous RNA (ceRNA) interactions. Using high-throughput validation assays in breast cancer cell lines, we show that our integrative approach significantly improves on microRNA-target prediction accuracy as assessed by both mRNA and protein level measurements. Our biochemical assays support nearly 500 microRNA-target interactions with evidence for regulation in breast cancer tumors. Moreover, these assays constitute the most extensive validation platform for computationally inferred networks of microRNA-target interactions in breast cancer tumors, providing a useful benchmark to ascertain future improvements.
Subject(s)
Computational Biology/methods , Epistasis, Genetic , Gene Regulatory Networks , MicroRNAs/genetics , RNA Interference , RNA, Messenger/genetics , 3' Untranslated Regions , Algorithms , Binding Sites , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Line, Tumor , Cluster Analysis , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/chemistry , RNA, Messenger/chemistryABSTRACT
The predominant view of pluripotency regulation proposes a stable ground state with coordinated expression of key transcription factors (TFs) that prohibit differentiation. Another perspective suggests a more complexly regulated state involving competition between multiple lineage-specifying TFs that define pluripotency. These contrasting views were developed from extensive analyses of TFs in pluripotent cells in vitro. An experimentally validated, genome-wide repertoire of the regulatory interactions that control pluripotency within the in vivo cellular contexts is yet to be developed. To address this limitation, we assembled a TF interactome of adult human male germ cell tumors (GCTs) using the Algorithm for the Accurate Reconstruction of Cellular Pathways (ARACNe) to analyze gene expression profiles of 141 tumors comprising pluripotent and differentiated subsets. The network (GCT(Net)) comprised 1,305 TFs, and its ingenuity pathway analysis identified pluripotency and embryonal development as the top functional pathways. We experimentally validated GCT(Net) by functional (silencing) and biochemical (ChIP-seq) analysis of the core pluripotency regulatory TFs POU5F1, NANOG, and SOX2 in relation to their targets predicted by ARACNe. To define the extent of the in vivo pluripotency network in this system, we ranked all TFs in the GCT(Net) according to sharing of ARACNe-predicted targets with those of POU5F1 and NANOG using an odds-ratio analysis method. To validate this network, we silenced the top 10 TFs in the network in H9 embryonic stem cells. Silencing of each led to downregulation of pluripotency and induction of lineage; 7 of the 10 TFs were identified as pluripotency regulators for the first time.
Subject(s)
Algorithms , Models, Biological , Neoplasm Proteins/metabolism , Neoplasms, Germ Cell and Embryonal/metabolism , Pluripotent Stem Cells/metabolism , Transcription Factors/metabolism , Adult , Cell Line, Tumor , Humans , Male , Neoplasm Proteins/genetics , Neoplasms, Germ Cell and Embryonal/genetics , Neoplasms, Germ Cell and Embryonal/pathology , Pluripotent Stem Cells/pathology , Transcription Factors/geneticsABSTRACT
BACKGROUND AND PURPOSE: Tolosa-Hunt Syndrome (THS) is a rare disorder, and detailed clinical information and treatment outcomes have yet to be fully elucidated. This study aims to investigate the clinical features and factors associated with the treatment outcomes of THS, as defined by the established diagnostic criteria. METHODS: This study retrospectively recruited 91 patients with a diagnosis of THS from 2003 to 2020. We analyzed the clinical features and outcomes, the initial treatment response, recurrences, and the final treatment response. RESULTS: Isolated ocular motor nerve palsy was the most common (82.4%) finding of ophthalmoplegia, involving the oculomotor nerve in more than half of the cases (52.0%). The MRI lesions were mostly observed in the cavernous sinus (94.5%) with an extracavernous extension in about one-third of them. Five patients showed only extracavernous lesions. A total of 25 (27.5%) patients experienced recurrence. Recurrence occurred during steroid tapering as part of the initial treatment in seven, while in 18 patients, it happened after the successful termination of the initial treatment. However, all patients achieved complete remission at the final. Age was associated with a decrease in initial symptom duration (HR = 1.023, CI = 1.004-1.044) as well as an increase in recurrence-free duration (HR = 0.944, CI = 0.911-0.978). High-dose corticosteroid treatment was associated with a decrease in initial symptom duration (HR = 1.642, CI = 1.001-2.695) and total treatment duration (HR = 2.203 CI = 1.302-3.730). CONCLUSIONS: THS can recur frequently especially in younger but have a favorable prognosis. High-dose corticosteroids can be an effective initial treatment and reduce the total treatment duration.
Subject(s)
Cavernous Sinus , Ophthalmoplegia , Tolosa-Hunt Syndrome , Humans , Tolosa-Hunt Syndrome/diagnosis , Tolosa-Hunt Syndrome/drug therapy , Tolosa-Hunt Syndrome/complications , Retrospective Studies , Cavernous Sinus/pathology , Magnetic Resonance Imaging , Adrenal Cortex Hormones/therapeutic use , Paralysis , RecurrenceABSTRACT
OBJECTIVES: This study sought to evaluate the efficacy of cancellous bovine bone mineral granules and 10% porcine collagen (deproteinized bovine bone mineral with collagen [DBBM-C]; (OCS-B Collagen® [Straumann XenoFlex], NIBEC, Korea) in a mouldable block form, with or without socket seal, using autogenous free gingival graft (FGG). METHODS: Fifty-four patients were included and randomly assigned to one of three groups: (1) spontaneous healing (control group), (2) alveolar ridge preservation (ARP) using DBBM-C (DBBM-C group), and (3) ARP employing DBBM-C sealed with FGG (DBBM-C/FGG group). Bone biopsy and implant fixture placement were performed 180 days after ARP. Cone-beam computed tomography, histological analysis, implant stability, and three-dimensional volumetric analysis were conducted. RESULTS: Of the 54 patients, 4 dropped out owing to loss of follow-up and osseointegration failure. The changes in alveolar bone during follow-up were not significantly different. Between 84- and 180-day postextraction, the volume of the DBBM-C and DBBM-C/FGG groups was maintained at 3 mm below the alveolar ridge crest (0.72 ± 0.80 mm, 6.05 ± 6.69%), whereas the volume in the control group decreased (-0.37 ± 1.31 mm, -2.10% ± 8.37%) (P = .026). The DBBM-C/FGG group exhibited less horizontal ridge resorption at 1 mm below the alveolar crest (-9.19 ± 5.09 mm, -73.67% ± 32.53%) between preextraction and 84 days postextraction (P = .049). In all groups, the implant stability quotient remained above 70. CONCLUSIONS: Within the limitations of this study, both ARP using DBBM-C with and without socket sealing effectively preserved the width dimension of the alveolar ridge, with no significant difference in alveolar bone resorption. However, socket sealing appeared to enhance the stability of the bone graft and bone quality. CLINICAL RELEVANCE: The use of DBBM-C for ARP seems to aid in volume maintenance as compared with spontaneous healing. Gingival sealing with an FGG can help maintain the width of the alveolar ridge. This clinical trial was not registered prior to participant recruitment and randomization. This study was registered at WHO ICTRP (https://trialsearch.who.int/Trial2.aspx?TrialID=KCT0008266).
ABSTRACT
Obesity is primarily exacerbated by excessive lipid accumulation during adipogenesis, with triacylglycerol (TG) as a major lipid marker. However, as the association between numerous lipid markers and various health conditions has recently been revealed, investigating the lipid metabolism in detail has become necessary. This study investigates the lipid metabolic effects of Hydrangea serrata (Thunb.) Ser. hot water leaf extract (WHS) on adipogenesis using LC-MS-based lipidomics analysis of undifferentiated, differentiated, and WHS-treated differentiated 3T3-L1 cells. WHS treatment effectively suppressed the elevation of glycerolipids, including TG and DG, and prevented a molecular shift in fatty acyl composition towards long-chain unsaturated fatty acids. This shift also impacted glycerophospholipid metabolism. Additionally, WHS stabilized significant lipid markers such as the PC/PE and LPC/PE ratios, SM, and Cer, which are associated with obesity and related comorbidities. This study suggests that WHS could reduce obesity-related risk factors by regulating lipid markers during adipogenesis. This study is the first to assess the underlying lipidomic mechanisms of the adipogenesis-inhibitory effect of WHS, highlighting its potential in developing natural products for treating obesity and related conditions. Our study provides a new strategy for the development of natural products for the treatment of obesity and related diseases.
Subject(s)
3T3-L1 Cells , Adipogenesis , Hydrangea , Lipid Metabolism , Lipidomics , Plant Extracts , Plant Leaves , Adipogenesis/drug effects , Plant Extracts/pharmacology , Plant Leaves/chemistry , Animals , Mice , Hydrangea/chemistry , Lipid Metabolism/drug effects , Water/chemistry , Adipocytes/drug effects , Adipocytes/metabolism , Triglycerides/metabolism , Obesity/prevention & controlABSTRACT
Genetically modified organisms (GMOs) have been continuously developed for their convenience and productivity. In the past three years, three new GM canola events (MON94100, LBFLFK, and NS-B50027-4) have been developed. To efficiently control these GM canola events, the detection methods were needed. Therefore, the multiplex PCR method combined with capillary electrophoresis was developed for three GM canola events. Ten GM canola, eighteen GM soybean, thirty-two GM maize, and ten non-GM crops were used to evaluate the specificity of the method. The detection limit of the multiplex PCR assay was determined to be 0.005 ng in the DNA mixture and 0.1% in the spiked sample. The aim of this study was to establish multiplex PCR coupled with capillary electrophoresis for the newly produced three GM canola events. The developed method is expected to contribute to monitor the commercially available GM canola events. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01377-z.
ABSTRACT
Obesity requires treatment to mitigate the potential development of further metabolic disorders, including diabetes, hyperlipidemia, tumor growth, and non-alcoholic fatty liver disease. We investigated the anti-obesity effect of a 30% ethanol extract of Eisenia bicyclis (Kjellman) Setchell (EEB) on 3T3-L1 preadipocytes and high-fat diet (HFD)-induced obese C57BL/6 mice. Adipogenesis transcription factors including peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein-alpha (C/EBPα), and sterol regulatory element-binding protein-1 (SREBP-1) were ameliorated through the AMP-activated protein kinase (AMPK) pathway by EEB treatment in differentiated 3T3-L1 cells. EEB attenuated mitotic clonal expansion by upregulating cyclin-dependent kinase inhibitors (CDKIs) while downregulating cyclins and CDKs. In HFD-fed mice, EEB significantly decreased the total body weight, fat tissue weight, and fat in the tissue. The protein expression of PPARγ, C/EBPα, and SREBP-1 was increased in the subcutaneous fat and liver tissues, while EEB decreased the expression levels of these transcription factors. EEB also inhibited lipogenesis by downregulating acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) expression in the subcutaneous fat and liver tissues. Moreover, the phosphorylation of AMPK and ACC was downregulated in the HFD-induced mouse group, whereas the administration of EEB improved AMPK and ACC phosphorylation; thus, EEB treatment may be related to the AMPK pathway. Histological analysis showed that EEB reduced the adipocyte size and fat accumulation in subcutaneous fat and liver tissues, respectively. EEB promotes thermogenesis in brown adipose tissue and improves insulin and leptin levels and blood lipid profiles. Our results suggest that EEB could be used as a potential agent to prevent obesity.
Subject(s)
3T3-L1 Cells , AMP-Activated Protein Kinases , Anti-Obesity Agents , Diet, High-Fat , Mice, Inbred C57BL , Obesity , Plant Extracts , Signal Transduction , Animals , Mice , Diet, High-Fat/adverse effects , Plant Extracts/pharmacology , AMP-Activated Protein Kinases/metabolism , AMP-Activated Protein Kinases/genetics , Male , Anti-Obesity Agents/pharmacology , Obesity/drug therapy , Obesity/metabolism , Signal Transduction/drug effects , Sterol Regulatory Element Binding Protein 1/metabolism , Sterol Regulatory Element Binding Protein 1/genetics , Adipogenesis/drug effects , PPAR gamma/metabolism , PPAR gamma/genetics , CCAAT-Enhancer-Binding Protein-alpha/metabolism , CCAAT-Enhancer-Binding Protein-alpha/genetics , Adipocytes/drug effects , Adipocytes/metabolism , Edible Seaweeds , KelpABSTRACT
Hepatocellular carcinoma frequently recurs after surgery, necessitating personalized clinical approaches based on tumor avatar models. However, location-dependent oxygen concentrations resulting from the dual hepatic vascular supply drive the inherent heterogeneity of the tumor microenvironment, which presents challenges in developing an avatar model. In this study, tissue samples from 12 patients with hepatocellular carcinoma are cultured directly on a chip and separated based on preference of oxygen concentration. Establishing a dual gradient system with drug perfusion perpendicular to the oxygen gradient enables the simultaneous separation of cells and evaluation of drug responsiveness. The results are further cross-validated by implanting the chips into mice at various oxygen levels using a patient-derived xenograft model. Hepatocellular carcinoma cells exposed to hypoxia exhibit invasive and recurrent characteristics that mirror clinical outcomes. This chip provides valuable insights into treatment prognosis by identifying the dominant hepatocellular carcinoma type in each patient, potentially guiding personalized therapeutic interventions.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Oxygen , Tumor Microenvironment , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Humans , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Animals , Mice , Oxygen/metabolism , Cell Line, Tumor , Male , Female , Xenograft Model Antitumor Assays , Middle Aged , Lab-On-A-Chip DevicesABSTRACT
Vibratory stimulation of the sternocleidomastoid muscles or the skull may enhance vestibular asymmetry and evoke nystagmus. We report prominent downbeating vibration-induced nystagmus (VIN) in a patient with paraneoplastic cerebellar degeneration due to cervical cancer with positive serum anti-Ri antibody. A 47-year-old woman developed spontaneous upbeat nystagmus present with and without visual fixation. Nystagmus decreased during lateral and upward gaze. Downbeat nystagmus emerged during convergence and after horizontal head shaking for approximately 15 seconds and during vibratory stimulation of the mastoids and forehead. Additional findings included positional downbeat nystagmus, impaired smooth pursuit, hypermetric horizontal saccades, and truncal ataxia. During video-head impulse tests, the gains of the vestibulo-ocular reflex (VOR) were normal for both horizontal semicircular canals but increased for both anterior canals and decreased for both posterior canals. Horizontal head impulses produced cross-coupled downward corrective saccades. Given the asymmetric vertical VOR, downbeat VIN observed in our patient may be ascribed to enhanced upward bias of the VOR due to vestibulocerebellar dysfunction during the vibratory stimuli. Vibration-induced downbeat nystagmus should be added to the list of central vestibular signs and is likely due to cerebellar dysfunction.
Subject(s)
Nystagmus, Pathologic , Paraneoplastic Cerebellar Degeneration , Female , Humans , Middle Aged , Vibration , Saccades , Reflex, Vestibulo-Ocular/physiology , Paraneoplastic Cerebellar Degeneration/complicationsABSTRACT
Biomedical relation extraction (BioRE) is the task of automatically extracting and classifying relations between two biomedical entities in biomedical literature. Recent advances in BioRE research have largely been powered by supervised learning and large language models (LLMs). However, training of LLMs for BioRE with supervised learning requires human-annotated data, and the annotation process often accompanies challenging and expensive work. As a result, the quantity and coverage of annotated data are limiting factors for BioRE systems. In this paper, we present our system for the BioCreative VII challenge-DrugProt track, a BioRE system that leverages a language model structure and weak supervision. Our system is trained on weakly labelled data and then fine-tuned using human-labelled data. To create the weakly labelled dataset, we combined two approaches. First, we trained a model on the original dataset to predict labels on external literature, which will become a model-labelled dataset. Then, we refined the model-labelled dataset using an external knowledge base. Based on our experiment, our approach using refined weak supervision showed significant performance gain over the model trained using standard human-labelled datasets. Our final model showed outstanding performance at the BioCreative VII challenge, achieving 3rd place (this paper focuses on our participating system in the BioCreative VII challenge). Database URL: http://wonjin.info/biore-yoon-et-al-2022.
Subject(s)
Biomedical Research , Language , Humans , Databases, FactualABSTRACT
BACKGROUND: Rugby showed a high incidence of exertional heatstroke. Different physiques and running performances between the forward and back players (FW and BK) may result in different heatstroke risks. This study aimed to compare the hydration status, running performance, and perceived heatstroke symptoms (PHS) between cool and hot environment training (HT and CT) in university rugby union FW and BK. METHODS: Thirteen university rugby players (seven forwards and six backs) participated in this study. During both conditions, players were allowed to drink water and sports drink, and the amount of fluid intake was recorded. Body mass was measured pre- and post-training, and weight loss was calculated. Sweat loss was calculated based on body mass and fluid intake. During training, running performance was measured using GPS. The presence of PHS was assessed using a questionnaire administered after training. RESULTS: Fluid intake and sweat loss were higher in the HT as opposed to the CT, and FW showed higher fluid intake and dehydration than BK. However, there were no significant differences in weight loss observed during data collection. Running distance per minute and maximum speed were higher in BK than in FW, but there was no significant difference between conditions. Although a significant weight loss was not observed between conditions, the number of PHS was higher in the HT. CONCLUSIONS: Although BK had a higher running distance and maximum speed than FW during training, a higher cycle of fluid intake and sweat loss was observed in the FW than that in the BK.
Subject(s)
Athletic Performance , Heat Stroke , Running , Humans , Rugby , Drinking , Sweating , Weight LossABSTRACT
BACKGROUND AND OBJECTIVES: The etiologic distribution and clinical features of diplopia may differ according to the specialties involved in the management. This study aimed to establish the clinical features and underlying etiologies of diplopia by recruiting patients from all departments. METHODS: We reviewed the medical records of 4127 patients with diplopia as the chief complaint, who had been recruited from all departments at Seoul National University Bundang Hospital, Seongnam, Republic of Korea, from 2003 to 2020. RESULTS: Diplopia was binocular in 3557 (94.2%) and monocular in 219 (5.8%) patients. The common causes of binocular diplopia included microvascular (n = 516, 14.5%), strokes (n = 412, 11.6%), neoplastic (n = 304, 8.5%), myasthenia gravis (n = 253, 7.1%), traumatic (n = 240, 6.7%), and decompensated phoria (n = 232, 6.5%), and comprised more than a half of the causes. Patients with binocular diplopia were usually managed by neurologists (2549/3557, 71.7%), followed by ophthalmologists (2247/3557, 63.2%), emergency physicians (1528/3557, 43.0%), neurosurgeons (361/3557, 10.1%), and others (271/3557, 7.6%). The etiologies of binocular diplopia differed markedly according to the patients' age and the specialties involved in the management (p < 0.001). CONCLUSIONS: Given the differences in the etiologic distribution of diplopia according to the patients' age and the specialties involved in the management, the results of previous reports on the characteristics and etiology of diplopia, primarily performed in a single specialty department, should be interpreted with a possible selection bias.