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1.
Sleep Med ; 124: 371-377, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39383798

RESUMO

BACKGROUND: This study aimed to investigate the association of the grit scale, a personality trait characterized by perseverance and passion, with both the presence and the severity of insomnia in the Korean adult population. METHODS: A nationwide population-based cross-sectional survey was conducted through face-to-face interviews using structured questionnaires between September and December 2018 in Korea. Grit was assessed by using the 8-item Short Grit Scale. Participants were categorized into insomnia and non-insomnia groups based on a threshold of 10 on the Insomnia Severity Index (ISI). The association between girt and insomnia was analyzed using multiple linear regression and multivariable logistic regression, controlling for sociodemographic factors, lifestyles, and comorbidities. RESULTS: A total of 2453 participants (49.9 % male; aged 19-92 years) were enrolled in the study. Individual grit scores ranged from 1.75 to 5.00 points (mean [SD], 3.27 [0.42]), and insomnia was present in 16.5 % of the population. The insomnia group exhibited lower grit score compared to the non-insomnia group (3.11 [0.40] vs. 3.30 [0.42], p < 0.001, Cohen's d = 0.46). Grit was negatively associated with ISI scores (ß = -0.15, 95 % CI = -0.19, -0.11, p < 0.001) and with having insomnia (OR 0.40, 95 % CI = 0.30, 0.55, p < 0.001), after controlling for covariates. CONCLUSIONS: Individuals with higher grit were less likely to have insomnia. Clinicians should consider personality traits, such as grit, in the evaluation and the management of insomnia.

2.
Theranostics ; 14(12): 4713-4729, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239520

RESUMO

Background: Mesenchymal stem/stromal cells (MSCs) maintain tissue homeostasis in response to microenvironmental perturbations. Toll-like receptors (TLRs) are key sensors for exogenous and endogenous signals produced during injury. In this study, we aimed to investigate whether TLRs affect the homeostatic functions of MSCs after injury. Methods: We examined the expression of TLR2, TLR3 and TLR4 in MSCs, and analyzed the functional significance of TLR2 activation using single-cell RNA sequencing. Additionally, we investigated the effects and mechanisms of TLR2 and its downstream activation in MSCs on the MSCs themselves, on monocytes/macrophages, and in a mouse model of sterile injury-induced inflammatory corneal angiogenesis. Results: MSCs expressed TLR2, which was upregulated by monocytes/macrophages. Activation of TLR2 in MSCs promoted their immunoregulatory and angiostatic functions in monocytes/macrophages and in mice with inflammatory corneal angiogenesis, whereas TLR2 inhibition attenuated these functions. Single-cell RNA sequencing revealed AKR1C1, a gene encoding aldo-keto reductase family 1 member C1, as the most significantly inducible gene in MSCs upon TLR2 stimulation, though its stimulation did not affect cell compositions. AKR1C1 protected MSCs against ferroptosis, increased secretion of anti-inflammatory cytokines, and enhanced their ability to drive monocytes/macrophages towards immunoregulatory phenotypes, leading to the amelioration of inflammatory corneal neovascularization in mice. Conclusion: Our findings suggest that activation of TLR2-AKR1C1 signaling in MSCs serves as an important pathway for the survival and homeostatic activities of MSCs during injury.


Assuntos
Macrófagos , Células-Tronco Mesenquimais , Receptor 2 Toll-Like , Animais , Células-Tronco Mesenquimais/metabolismo , Camundongos , Receptor 2 Toll-Like/metabolismo , Receptor 2 Toll-Like/genética , Macrófagos/metabolismo , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Humanos , Neovascularização da Córnea/metabolismo , Neovascularização da Córnea/patologia , Neovascularização da Córnea/genética , Monócitos/metabolismo , Masculino , Receptor 4 Toll-Like/metabolismo , Modelos Animais de Doenças , Transdução de Sinais
3.
Sensors (Basel) ; 24(17)2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39275622

RESUMO

Colonoscopy has a limited field of view because it relies solely on a small camera attached to the end of the scope and a screen displayed on a monitor. Consequently, the quality and safety of diagnosis and treatment depend on the experience and skills of the gastroenterologist. When a novice attempts to insert the colonoscope during the procedure, excessive pressure can sometimes be applied to the colon wall. This pressure can cause a medical accident known as colonic perforation, which the physician should prevent. We propose an assisting device that senses the pressure applied to the colon wall, analyzes the risk of perforation, and warns the physician in real time. Flexible pressure sensors are attached to the surface of the colonoscope shaft. These sensors measure pressure signals during a colonoscopy procedure. A simple signal processor is used to collect and process the pressure signals. In the experiment, a colonoscope equipped with the proposed device was inserted into a simulated colon made from a colon extracted from a pig. The processed data were visually communicated to the gastroenterologist via displays and light-emitting diodes (LEDs). The device helps the physician continuously monitor and prevent excessive pressure on the colon wall. In this experiment, the device appropriately generated and delivered warnings to help the physicians prevent colonic perforation. In the future, the device is to be improved, and more experiments will be performed in live swine models or humans to confirm its efficacy and safety.


Assuntos
Colo , Colonoscopia , Perfuração Intestinal , Pressão , Colonoscopia/instrumentação , Colonoscopia/métodos , Suínos , Colo/diagnóstico por imagem , Humanos , Animais , Perfuração Intestinal/prevenção & controle , Colonoscópios , Desenho de Equipamento
4.
Biosens Bioelectron ; 267: 116681, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39277921

RESUMO

Conjunctival goblet cells (CGCs) are specialized epithelial cells playing key roles for ocular surface homeostasis, and their examination is important for diagnosing ocular surface diseases. Despite recent advancements in high-contrast CGC imaging for non-invasive examination, significant challenges remain for human applications. High-speed large-area imaging over the curved ocular surface is needed to assess statistically meaningful CGCs in the extensive human conjunctiva. To address this challenge, we developed a novel surface detection method and an integrated microscopy system for human use. With both a long detection range of 2 mm and a high update rate of 50 Hz, the surface detection method enabled real-time surface tracking during large-area imaging. The integrated microscopy could complete 5 × 2 patch imaging in approximately 10 s. CGC density analysis showed significantly reduced uncertainties with large-area imaging. This is the first demonstration of non-contact large-area cellular examination in humans, and this new development holds promise for non-invasive CGC examination and accurate diagnosis of ocular surface diseases.

5.
Oncology ; : 1-16, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39278213

RESUMO

Introduction This study aims to assess the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in two groups of patients: those who receive lipiodol (referred to as the lipiodol group) and those who do not receive lipiodol (referred to as the control group). Methods From January 2016 through December 2023, 85 patients with advanced hepatocellular carcinoma were enrolled in this retrospective study. In total, 40 patients received HAIC with lipiodol, while 45 patients were given HAIC without lipiodol. The modified response evaluation criteria for solid tumors were used to evaluate the tumor response, which was assessed through an imaging study. The two groups were compared regarding their overall survival, progression-free survival, and safety. Results: The outcomes between the lipiodol group and control group demonstrated no significant difference: the objective response rates (P = 0.066) were 32.5% and 15.6%; the disease control rates (P = 0.556) were 67.5% and 73.3%; the median overall survival times (P = 0.339) were 224 days and 398 days; the median progression-free survival (P = 0.334) times were 191 days and 286 days in the lipiodol group and the control group, respectively. Adverse events also showed no significant difference between the two groups: elevation of total bilirubin (P = 0.834) rates were 40.0% and 37.8%; elevation of alanine aminotransferase (P = 0.191) percentages were 35.0% and 22.2%; and elevation of aspartate aminotransferase values (P = 0.058) were 65.0% and 44.4% in the lipiodol group and the control group, respectively. Conclusions: HAIC without lipiodol was non-inferior to HAIC with lipiodol in the clinical outcome.

6.
Vaccines (Basel) ; 12(9)2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39340070

RESUMO

(1) Background: Shift work can affect physical health and the immune system by altering the body's circadian rhythms. This study investigated the factors associated with the hepatitis B virus (HBV) vaccination response in manufacturing workers, classified by whether they engaged in shift work or not. (2) Methods: This retrospective observational study was conducted among adults employed at two manufacturing companies. Those with negative initial hepatitis B surface antibody (HBsAb) levels before vaccination and who subsequently received a three-dose series of HBV vaccine were enrolled. Hepatitis B surface antibodies were examined for 3 years after the first dose. The endpoint of this study was the failure of a seroprotective anti-HB response after vaccination (HBsAb < 10 mIU/mL). Binary logistic regression models were used to analyze factors associated with response failures. (3) Results: Of the 1103 eligible subjects, 337 (30.6%) were shift workers. The failure rate was numerically higher in the shift workers (9.2%) than in the non-shift workers (7.9%), without statistical significance (p = 0.405). However, after adjustment with the binary logistic regression models, the shift workers had a statistically significantly higher rate of response failures than the non-shift workers (odds ratio 2.87; 95% confidence interval 1.64-5.05, p < 0.001), as did males, older workers, those with a low initial anti-HB titer, those with a vitamin D deficiency, and current smokers. (4) Conclusions: Our findings suggest a possible association between shift work and the serologic responses to HBV vaccination. Novel strategies for vaccination should be considered for shift workers.

7.
Medicine (Baltimore) ; 103(39): e39848, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39331932

RESUMO

RATIONALE: Neuroendocrine carcinoma originating from extrahepatic bile duct is very rare, and only a few cases have been reported. Because of its scarcity of incidence, not much is known about the disease but for its aggressiveness and poor prognosis. PATIENT CONCERNS: In this report, we present 2 cases of large cell neuroendocrine carcinoma (LCNEC) originating from extrahepatic bile duct. Case 1: a 60-year-old woman presented with jaundice but no abdominal pain. Case 2: a 67-year-old man also presented with jaundice, along with abdominal discomfort and appetite loss. DIAGNOSES: Case 1: LCNEC with a focal adenocarcinoma component (pT2aN1M0, pStage IIIB). Case 2: LCNEC with a focal adenocarcinoma component (pT1N1M0, pStage IIB). INTERVENTIONS: Case 1: the patient underwent left hepatectomy and caudatectomy with hepaticojejunostomy, followed by 6 cycles of adjuvant chemotherapy (etoposide and cisplatin). Case 2: the patient underwent laparoscopic pylorus-preserving pancreatoduodenectomy, followed by 6 cycles of adjuvant chemotherapy (etoposide and cisplatin). OUTCOMES: Case 1: liver metastasis was detected 6 months postoperatively, and despite multiple chemotherapy regimens, the patient died 24 months post-surgery. Case 2: liver metastasis was detected 23 months postoperatively. The patient is still alive 36 months post-surgery after receiving multiple chemotherapy regimens and radiotherapy. LESSONS: Given the rarity of LCNEC, it is essential to continue collecting and reporting additional case studies to build a more comprehensive understanding of the disease. Although the prognosis for LCNEC is generally poor, the use of a multidisciplinary approach and further research will be critical in developing more effective treatment strategies in the future.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Neuroendócrino , Humanos , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/terapia , Feminino , Quimioterapia Adjuvante/métodos , Pessoa de Meia-Idade , Idoso , Masculino , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Carcinoma de Células Grandes/cirurgia , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/terapia , Evolução Fatal , Hepatectomia/métodos , Pancreaticoduodenectomia/métodos , Ductos Biliares Extra-Hepáticos/patologia , Ductos Biliares Extra-Hepáticos/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
8.
Eur J Med Genet ; 72: 104972, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39293509

RESUMO

Heterozygous variants of MATN3 is one of the common causes of multiple epiphyseal dysplasia (MED). Here we report three individuals from two unrelated families who harbor compound heterozygous variants in MATN3 (p.Arg121Trp and p.Val220Ala). Contrary to the MED phenotype, these individuals exhibit spondyloepimetaphyseal dysplasia (SEMD) resembling the phenotypes caused by homozygous MATN3 variants. Clinical manifestations included short stature, aggravating genu varum, joint laxity, and spinal abnormalities. Radiographic findings were distinct from typical MED. These compound heterozygous variants in the von Willebrand factor A domain of MATN3 expand the phenotypic spectrum associated with MATN3, and suggest that extreme MATN3 dysfunction resulting from dual variants can lead to a specific pattern of SEMD.

9.
Curr Issues Mol Biol ; 46(9): 10606-10617, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39329980

RESUMO

Citrus unshiu Marc. cv. Miyagawa-wase is one of the most widely cultivated citrus varieties on Jeju Island in Republic of Korea. Mutation breeding is a useful tool for inducing genetic diversity by causing genomic mutations in a short period of time. We previously conducted mutation breeding using gamma irradiation to develop new varieties of C. unshiu. Here, we describe one of these varieties, Yein-early, which has a redder peel, greater hardness, and higher sugar content compared with the wild type (WT). Yein-early leaves also showed a unique phenotype compared with the WT, characterized by longer longitudinal length, shorter transverse length, stronger curling, and longer petiole length. Genome resequencing of Yein-early and the WT uncovered significant single-nucleotide polymorphisms (SNPs) and insertions/deletions (InDels). These variations were crucial in identifying molecular markers unique to Yein-early. In addition, we developed an allele-specific PCR marker specifically targeting a homozygous SNP in Yein-early that distinguishes it from the WT and other citrus varieties. This study contributes to the understanding of pigment synthesis in fruits and provides a valuable tool for selection of the novel Yein-early variety in citrus breeding programs.

10.
Cornea ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39288434

RESUMO

PURPOSE: The aim of this study was to investigate the efficacy of RCI001 (RCI) in a mouse model of primary Sjögren syndrome. METHODS: Eight 12-week-old NOD.B10-H2b mice were used in this study. All experimental animals were randomly divided into phosphate-buffered saline (PBS) and RCI groups in NOD.B10-H2b mice. The eyes of mice were topically treated with PBS or RCI twice a day for a week. Ocular surface staining (OSS) and tear secretion were compared between before and after treatment. The transcript levels of inflammatory cytokines and nicotinamide adenine dinucleotide phosphate oxidase (NOX) in the conjunctiva and cornea (CC) and lacrimal gland were assayed. In addition, immunofluorescence staining of the conjunctiva was assessed. RESULTS: The RCI group showed significant clinical improvement in OSS and tear secretion after 1 week of treatment compared with the baseline (both P < 0.001) and showed better improvement in OSS and tear secretion than the PBS group after 1 week of treatment (both P < 0.05). The levels of IL-1ß and IL-17 in CC and IL-6 in the lacrimal gland were also significantly reduced in the RCI group compared with the PBS group (each P < 0.05). Transcript levels of NOX2 and NOX4 were also significantly reduced in CC of the RCI group compared with those of the PBS group (P < 0.05). The RCI group also resulted in lower conjunctival expression of oxidative stress markers (4-hydroxy-2-nonenal, hexanoyl-lysine, and NOX4) than the PBS group. CONCLUSIONS: Topical RCI001 demonstrated excellent therapeutic efficacy in a mouse model of primary Sjögren syndrome by inhibiting inflammation and oxidative stress.

11.
Artigo em Inglês | MEDLINE | ID: mdl-39322187

RESUMO

Background: Adrenocortical carcinomas (ACCs) are rare tumors with aggressive but varied prognosis. Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score, based on clinical and pathological factors, was found to best stratify the prognosis of European ACC patients. This study assessed the prognostic performance of modified S-GRAS (mS-GRAS) scores including modified grade (mG) by integrating mitotic counts into the Ki67 index (original grade), in Korean ACC patients. Methods: Patients who underwent surgery for ACC between January 1996 and December 2022 at three medical centers in Korea were retrospectively analyzed. mS-GRAS scores were calculated based on tumor stage, mG (Ki67 index or mitotic counts), resection status, age, and symptoms. Patients were divided into four groups (0-1, 2-3, 4-5, and 6-9 points) based on total mS-GRAS score. The associations of each variable and mS-GRAS score with recurrence and survival were evaluated using Cox regression analysis, Harrell's concordance index (C-index), and the Kaplan-Meier method. Results: Data on mS-GRAS components were available for 114 of the 153 patients who underwent surgery for ACC. These 114 patients had recurrence and death rates of 61.4% and 48.2%, respectively. mS-GRAS score was a significantly better predictor of recurrence (C-index=0.829) and death (C-index=0.747) than each component (P<0.05), except for resection status. mS-GRAS scores correlated with shorter progression-free survival (P=8.34E-24) and overall survival (P=2.72E-13). Conclusion: mS-GRAS scores showed better prognostic performance than tumor stage and grade in Asian patients who underwent surgery for ACC.

12.
Sci Rep ; 14(1): 22110, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333226

RESUMO

This study aims to develop a theoretical model for predicting the permeability of concrete in underground structures using compressive elastic waves. This research is motivated by the necessity of monitoring the permeability of concrete used in critical underground infrastructure, such as tunnels and radioactive waste disposal sites, to ensure their long-term safety. Increased permeability owing to crack generation can lead to groundwater inflow, undermining the structural integrity of these facilities. Traditional methods for permeability monitoring face challenges at depths of 500 m-1 km owing to high temperatures, high pressures, and limited space conditions. To address these issues, Biot's model, which correlates the P-wave characteristics with the properties of porous media, was applied in this study. The P-wave velocity and attenuation were studied according to the permeability of concrete based on Biot's model. Subsequently, concrete specimens were prepared to measure the permeability, P-wave velocity, and attenuation. The permeability results from the experiment were compared with those obtained from the model for validation. The findings indicate that the modified Biot's model can effectively monitor permeability through elastic wave characteristics, offering a non-destructive and reliable method for assessing the condition of concrete structures in underground environments. This approach is expected to enhance the safety of underground infrastructure through accurate permeability monitoring.

13.
Orthop J Sports Med ; 12(7): 23259671241256445, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39100212

RESUMO

Background: A recent study has reported that the radiographic measurement of posterior tibial slope (PTS) is larger in male pediatric patients with tibial spine fractures (TSF) than in controls. However, they found no difference in PTS between female patients and controls. Purpose: (1) To identify whether PTS is larger in female pediatric patients with TSF than in female controls and (2) to validate the relationship between PTS and pediatric TSF in male patients. Study Design: Cross-sectional study; Level of evidence, 3. Methods: After an a priori power analysis, 84 pediatric patients with TSF (50 female patients and 34 male patients) and 84 age- and sex-matched controls were enrolled in this study. Demographic information, including sex, age, and race, was recorded. Skeletal maturity was determined based on the stage of epiphyseal union on knee radiographs. PTS was defined as the angle between a line perpendicular to the longitudinal axis of the tibia and the posterior inclination of the medial tibial plateau on standard knee lateral radiographs. Results: The mean age when the TSF occurred was 11.2 ± 2.7 years for female patients and 12.9 ± 2.5 years for male patients. There was no significant difference in skeletal maturity between female patients and female controls or between male patients and male controls. The mean PTS was not significantly different between female patients (8.8°± 2.8°) and female controls (8.3°± 3.1°) (P = .366) or between male patients (9.0°± 2.8°) and male controls (9.3°± 2.6°) (P = .675). Those with a PTS >1 SD (2.9°) above the mean (8.8°) had no greater odds (1.0 [95% CI, 0.4-2.5]; P≥ .999) of having a TSF than others. Conclusion: PTS was not found to be a risk factor for pediatric TSF in female or male patients in this study.

14.
Curr Med Imaging ; 20: e15734056277516, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39087635

RESUMO

OBJECTIVE: The study aimed to evaluate whether the measurement of Femoral Neck Shaft Angle (FNSA) can be helpful in differentiating femoral head Stress Fracture (SF) from Avascular Necrosis (AVN). METHODS: From September 2019 to April 2022, sixty-four patients [median age 32.0 years, interquartile range (IQR) 23.0-39.0 years] who underwent both hip radiograph and Magnetic Resonance Imaging (MRI) and diagnosed as femoral head SF or AVN were included in our retrospective study. Patients were divided into as having either femoral head SF (n = 34) or AVN (n = 30). The FNSA was measured in anteroposterior hip radiography. Continuous values were compared using the Mann-Whitney U test. The assessment of the predictive value of FNSA for femoral head SF was performed by Receiver Operating Characteristic (ROC) analysis. RESULTS: The FNSA was significantly higher in patients with SF (median 133.5°, IQR 128.0-136.7°) than those with AVN (median 127.5°, IQR 124.0-132.0°) (p = 0.001). In addition, the FNSA was significantly higher in SF femurs (median 134.8°, IQR 129.2-137.4°) than in contralateral normal femurs (median 127.1°, IQR 124.3-132.5°) in patients with unilateral femoral head SF (n = 30) (p < 0.001). In ROC analysis, the sensitivity, specificity, and Area Under the Curve (AUC) for predicting the femoral head SF were 77.3%, 63.3%, and 0.785 (95% confidence interval: 0.666-0.905), respectively, at a cutoff of 130.2°. CONCLUSION: Increased FNSA was associated with femoral head SF; thus, measurement of FNSA could be helpful for differentiating femoral head SF from AVN.


Assuntos
Necrose da Cabeça do Fêmur , Colo do Fêmur , Fraturas de Estresse , Imageamento por Ressonância Magnética , Humanos , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Masculino , Feminino , Adulto , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Diagnóstico Diferencial , Fraturas de Estresse/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Adulto Jovem , Curva ROC , Fraturas do Colo Femoral/diagnóstico por imagem , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/lesões , Radiografia/métodos , Pessoa de Meia-Idade
15.
Endocrinol Metab (Seoul) ; 39(4): 622-631, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39086276

RESUMO

BACKGRUOUND: Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently prescribed for patients with type 2 diabetes; however, their cost can pose a significant barrier for those with impaired kidney function. This study aimed to estimate the economic benefits of substituting non-renal dose-adjusted (NRDA) DPP4 inhibitors with renal dose-adjusted (RDA) DPP4 inhibitors in patients with both impaired kidney function and type 2 diabetes. METHODS: This retrospective cohort study was conducted from January 1, 2012 to December 31, 2018, using data obtained from common data models of five medical centers in Korea. Model 1 applied the prescription pattern of participants with preserved kidney function to those with impaired kidney function. In contrast, model 2 replaced all NRDA DPP4 inhibitors with RDA DPP4 inhibitors, adjusting the doses of RDA DPP4 inhibitors based on individual kidney function. The primary outcome was the cost difference between the two models. RESULTS: In total, 67,964,996 prescription records were analyzed. NRDA DPP4 inhibitors were more frequently prescribed to patients with impaired kidney function than in those with preserved kidney function (25.7%, 51.3%, 64.3%, and 71.6% in patients with estimated glomerular filtration rates [eGFRs] of ≥60, <60, <45, and <30 mL/min/1.73 m2, respectively). When model 1 was applied, the cost savings per year were 7.6% for eGFR <60 mL/min/1.73 m2 and 30.4% for eGFR <30 mL/min/1.73 m2. According to model 2, 15.4% to 51.2% per year could be saved depending on kidney impairment severity. CONCLUSION: Adjusting the doses of RDA DPP4 inhibitors based on individual kidney function could alleviate the economic burden associated with medical expenses.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Insuficiência Renal Crônica , Humanos , Inibidores da Dipeptidil Peptidase IV/economia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/economia , Diabetes Mellitus Tipo 2/complicações , Estudos Retrospectivos , Masculino , Insuficiência Renal Crônica/economia , Feminino , Pessoa de Meia-Idade , Idoso , Análise Custo-Benefício , República da Coreia , Taxa de Filtração Glomerular
16.
Biosens Bioelectron ; 263: 116630, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39102773

RESUMO

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is facilitated by its trimeric surface spike protein, which binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. This critical interaction facilitates viral entry and is a primary target for therapeutic intervention against COVID-19. However, it is difficult to fully optimize viral infection using existing protein-protein interaction methods. Herein, we introduce a nano-luciferase binary technology (NanoBiT)-based pseudoviral sensor designed to stimulate the dynamics of viral infection in both living cells and animals. Infection progression can be dynamically visualized via a rapid increase in luminescence within 3 h using an in vivo imaging system (IVIS). Inhibition of viral infection by baicalein and baicalin was evaluated using a NanoBiT-based pseudoviral sensor. These results indicate that the inhibitory efficacy of baicalein was strengthened by targeting the spike protein, whereas baicalin targeted the hACE2 protein. Additionally, under optimized conditions, baicalein and baicalin provided a synergistic combination to inhibit pseudoviral infection. Live bioluminescence imaging was used to evaluate the in vivo effects of baicalein and baicalin treatment on LgBiT-hACE2 mice infected with the BA.2-SmBiT spike pseudovirus. This innovative bioluminescent system functions as a sensitive and early-stage quantitative viral transduction in vitro and in vivo. This platform provides novel opportunities for studying the molecular biology of animal models.


Assuntos
Enzima de Conversão de Angiotensina 2 , Técnicas Biossensoriais , COVID-19 , Flavanonas , Flavonoides , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Animais , Técnicas Biossensoriais/métodos , Humanos , SARS-CoV-2/efeitos dos fármacos , Flavonoides/farmacologia , Flavonoides/química , Flavanonas/farmacologia , Flavanonas/química , Camundongos , COVID-19/virologia , Antivirais/farmacologia , Antivirais/química , Tratamento Farmacológico da COVID-19 , Células HEK293
18.
Clin Cancer Res ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39150517

RESUMO

PURPOSE: Anti-PD-1/L1 has been demonstrated for its efficacy when combined with cytotoxic chemotherapy in randomized phase 3 trials for advanced biliary tract cancer (BTC). However, no biomarker predictive of benefit has been established for anti-PD-1/L1 in BTC. Here, we evaluated tumor-infiltrating lymphocytes (TILs) using artificial intelligence-powered immune phenotype (AI-IP) analysis in advanced BTC treated with anti-PD-1. PATIENTS AND METHODS: Pre-treatment H&E-stained whole-slide images from 339 advanced BTC patients who received anti-PD-1 as second-line treatment or beyond, were utilized for AI-IP analysis and correlative analysis between AI-IP and efficacy outcomes with anti-PD-1. Next, data and images of BTC cohort from The Cancer Genome Atlas (TCGA) were additionally analyzed to evaluate the transcriptomic and mutational characteristics of various AI-IPs in BTC. RESULTS: Overall, AI-IPs were classified as inflamed (high intratumoral TIL [iTIL]) in 40 patients (11.8%), immune-excluded (low iTIL and high stromal TIL) in 167 (49.3%), and immune-deserted (low TIL overall) in 132 (38.9%). The inflamed IP group showed a significantly higher overall response rate compared to the non-inflamed IP groups (27.5% vs. 7.7%, P<0.001). Median overall survival and progression-free survival were significantly longer in the inflamed IP group than in the non-inflamed IP group (OS: 12.6 vs. 5.1 months, P=0.002; PFS: 4.5 vs. 1.9 months, P<0.001). In the analysis using TCGA cohort, the inflamed IP showed increased cytolytic activity scores and an interferon-gamma signature compared to the non-inflamed IP. CONCLUSIONS: AI-powered IP based on spatial TIL analysis was effective in predicting the efficacy outcomes in patients with BTC treated with anti-PD-1.

19.
Pleura Peritoneum ; 9(2): 55-61, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38948325

RESUMO

Objectives: The clinical significance of bacteremia in patients with complicated pleural infection is still uncertain. We aimed to examine the incidence and clinical significance of bacteremia in patients with complicated pleural infection. Methods: This retrospective study comprised of consecutive patients who received pleural drainage due to complicated parapneumonic effusion or empyema. The clinical, laboratory, and radiologic data and clinical outcome were compared between patients with and without bacteremia. Additionally, the factors associated with overall mortality were evaluated in these patients. Results: Of 341 patients included in the analysis, 25 (7 %) had a positive blood culture. Blood culture testing added 2 % identification of causative pathogen compared to pleural fluid culture alone. By multivariable analysis, radiologic features of cavitary lesion, a RAPID score≥5, and a positive microbial culture in pleural fluid were independently associated with bacteremia. Despite these clinical distinctions, there was ultimately no significant difference in in-hospital mortality between patients with and without bacteremia (3 vs. 4 %, p=1.0). The only factor significantly associated with overall mortality among patients with complicated pleural infections was a higher RAPID score [HR=1.96 (95 % CI=1.35-2.84)]. Conclusions: The rate of bacteremia in patients with complicated pleural infection was 7 %. Blood culture testing demonstrated limited diagnostic yield and had minimal impact on clinical outcomes compared to pleural fluid culture. Therefore, it seems that blood culture testing is more advantageous for specific patients with suspected pleural infection who have cavitary lesions or a RAPID score≥5.

20.
PLoS One ; 19(7): e0306627, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39058758

RESUMO

Photon-counting detector (PCD)-based computed tomography (CT) offers several advantages over conventional energy-integrating detector-based CT. Among them, the ability to discriminate energy exhibits significant potential for clinical applications because it provides material-specific information. That is, material decomposition (MD) can be achieved through energy discrimination. In this study, deep learning-based material decomposition was performed using live animal data. We propose MD-Unet, which is a deep learning strategy for material decomposition based on an Unet architecture trained with data from three energy bins. To mitigate the data insufficiency, we developed a pretrained model incorporating various simulation data forms and augmentation strategies. Incorporating these approaches into model training results in enhanced precision in material decomposition, thereby enabling the identification of distinct materials at individual pixel locations. The trained network was applied to the acquired animal data to evaluate material decomposition results. Compared with conventional methods, the newly generated MD-Unet demonstrated more accurate material decomposition imaging. Moreover, the network demonstrated an improved material decomposition ability and significantly reduced noise. In addition, they can potentially offer an enhancement level similar to that of a typical contrast agent. This implies that it can acquire images of the same quality with fewer contrast agents administered to patients, thereby demonstrating its significant clinical value.


Assuntos
Cálcio , Aprendizado Profundo , Iodo , Fótons , Tomografia Computadorizada por Raios X , Iodo/química , Tomografia Computadorizada por Raios X/métodos , Animais , Cálcio/análise , Processamento de Imagem Assistida por Computador/métodos , Meios de Contraste/química
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