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1.
Chembiochem ; : e202400468, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075031

RESUMEN

DNA condensates, formed by liquid-liquid phase separation (LLPS), emerge as promising soft matter assemblies for creating artificial cells. The advantages of DNA condensates are their molecular permeability through the surface due to their membrane-less structure and their fluidic property. However, they face challenges in the design of their surface, e.g., unintended fusion and less regulation of permeable molecules. Addressing them, we report surface modification of DNA condensates with DNA origami nanoparticles, employing a Pickering-emulsion strategy. We successfully constructed core-shell structures with DNA origami coatings on DNA condensates and further enhanced the condensate stability toward fusion via connecting DNA origamis by responding to DNA input strands. The 'armoring' prevented the fusion of DNA condensates, enabling the formation of multicellular-like structures of DNA condensates. Moreover, the permeability was altered through the state change from coating to armoring the DNA condensates. The armored DNA condensates have significant potential for constructing artificial cells, offering increased surface stability and selective permeability for small molecules while maintaining compartmentalized space and multicellular organization.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39002122

RESUMEN

OBJECTIVE: The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics, and efficacy (as an exploratory endpoint) of TCK-276, a novel CDK4/6 inhibitor, after multiple oral doses for 7 days in patients with active RA. METHODS: This multicentre, randomized, placebo-controlled, dose-ascending, double-blind, phase 1b, multiple-dose study included 32 patients with active RA in 4 cohorts of 8 patients (6 active and 2 matching placebo), each receiving an oral dose of TCK-276 or matching placebo for 7 days (once daily). The doses of TCK-276 were 10, 25, 75, and 175 mg/day. Safety and pharmacokinetic endpoints, and exploratory disease activity parameters for RA were assessed. RESULTS: There were no deaths, serious adverse events, notable clinically meaningful laboratory findings (including hematological changes), clinically meaningful vital sign changes, or clinically meaningful electrocardiogram or cardiac telemetry changes. TCK-276 was rapidly absorbed and the half-life time ranged approximately from 6 to 12 hours. No obvious accumulation was observed, and the increase in TCK-276 exposure was dose proportional. At day 7, DAS28-CRP responses (EULAR good or moderate responses) were observed in 40%, 80%, and 66.7% at 25, 75, and 175 mg/day TCK-276, respectively, versus 12.5% in placebo; ACR20 responses were 33.3%, 60%, and 50% respectively, versus none in placebo. CONCLUSION: TCK-276 (≤175 mg) was well tolerated with no clinically meaningful safety signals in patients with active RA. Together with the preliminary efficacy (≥25 mg/day), these data warrant further study of TCK-276 for the treatment of active RA. TRIAL REGISTRATION: ClinicalTrails.gov, NCT05437419.

3.
Neuropathology ; 44(4): 298-303, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38291581

RESUMEN

Although the initial symptoms of corticobasal degeneration (CBD) are varied, psychiatric symptoms are uncommon. Here, we report the autopsy findings of a patient with early CBD who presented with hallucinations. A 68-year-old man developed memory loss and visions of bears and insects. Because of slow vertical eye movement, postural instability, and levodopa-unresponsive parkinsonism, the patient initially was clinically diagnosed with progressive supranuclear palsy. He died of a urinary tract infection 11 months after the onset of the disease. Histopathological examination revealed neuronal loss and gliosis, which were severe in the substantia nigra and moderate in the globus pallidus and subthalamic nucleus. Astrocytic plaques were scattered throughout the amygdala and premotor cortex. The superficial cortical layers lacked ballooned neurons and spongiosis, and tau deposition was greater in glia than in neurons. The amygdala contained a moderate number of argyrophilic grains and pretangles. Western blot analysis showed a 37-kDa band among the low-molecular-weight tau fragments. Because the CBD pathology was mild, we attributed the patient's visual hallucinations to the marked argyrophilic grain pathology. CBD can occur with psychiatric symptoms, including visual hallucinations, and argyrophilic grain pathology may be associated with psychiatric symptoms.


Asunto(s)
Degeneración Corticobasal , Alucinaciones , Humanos , Masculino , Alucinaciones/patología , Alucinaciones/etiología , Anciano , Degeneración Corticobasal/patología , Degeneración Corticobasal/complicaciones
4.
J Orthop Sci ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39147648

RESUMEN

BACKGROUND: To evaluate the relationship between the pattern and severity of metatarsophalangeal (MTP) joint dislocation in the lesser toes and severity of joint destruction in rheumatoid forefoot deformities. METHODS: Participants comprised of 13 patients (16 feet) who underwent resection arthroplasty of the metatarsal head of the lesser toes for rheumatoid arthritis of the MTP joints. Correlations between preoperative radiographic findings and histological grades second to fifth metatarsal heads taken intraoperatively were analyzed. RESULTS: In 62 metatarsal heads, complete dislocation of the MTP joint in the lesser toes significantly resulted in severe joint destruction compared to mild or moderate dislocation (P < 0.05). The proportion of severe cartilage damage in MTP joints with complete dislocation was 100 % in the 5th MTP joint, 83.3 % in the 4th MTP joint, and 58.3 % in the 2nd and 3rd MTP joints. Moreover, complete dislocation of the MTP joints in the lateral column showed the most severe joint destruction compared to that in the medial column (P = 0.03). CONCLUSION: Complete dislocation of the MTP joint in the lateral column is related to joint destruction in rheumatoid forefoot deformities.

5.
BMJ Open Sport Exerc Med ; 10(1): e001720, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38511169

RESUMEN

Objectives: We aimed to assess the injury rate and characteristics in Japanese male professional ice hockey players. Methods: This study involved an inclusive cohort of male ice hockey players from a Japanese professional team competing in the 2010-2011 through the 2019-2020 seasons. An injury was defined as the 'time-loss and medical attention' definition of the International Ice Hockey Federation. All injuries that occurred during games and practice sessions were recorded daily on injury charts by the team athletic trainers and/or physician. Game-related injury rates were analysed using both the athlete-at-risk (AAR) and time on ice (TOI) methods. Results: Sixty players were included in the study. A total of 479 injuries were recorded, with 307 (64%) occurring during 451 games and 172 (36%) occurring during the practice sessions. The game-related injury rates obtained using the AAR and TOI methods were not statistically different (p>0.05): 115.3 (95% CI 107.1 to 123.1) and 116.8 (95% CI 109.9 to 124.7) per 1000 player-game hours, respectively. Most injuries involved the upper extremities (39.9% game-related, 32.6% practice-related), followed by the lower extremities (23.5% game-related, 32.5% practice-related). The most frequent mechanism of game-related injury was body checking (45.4%). Conclusion: We observed a higher injury rate in a Japanese male professional team compared with rates reported in other leagues. The reported injury characteristics should help to improve injury prevention strategies that should target shoulder dislocations caused by body checking, and finger or wrist fractures resulting from contact with a hockey stick or puck impact.

6.
PNAS Nexus ; 3(1): pgad437, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38156289

RESUMEN

This study describes the observation of the transformation of monomeric amyloid ß1-42 (Aß42) into oligomers in a lipid membrane utilizing a lipid bilayer system for electrophysiological measurement. The relevance of oligomers and protofibrils in Alzheimer's disease (AD) is underscored given their significant neurotoxicity. By closely monitoring the shift of Aß42 from its monomeric state to forming oligomeric channels in phospholipid membranes, we noted that this transformation transpired within a 2-h frame. We manipulated the lipid membrane's constitution with components such as glycerophospholipid, porcine brain total lipid extract, sphingomyelin (SM), and cholesterol (Chol.) to effectively imitate nerve cell membranes. Interesting findings showcased Chol.'s ability to foster stable oligomeric channel formation in the lipid membrane, with SM and GM1 lipids potentially enhancing channel formation as well. Additionally, the study identified the potential of a catechin derivative, epigallocatechin gallate (EGCG), in obstructing oligomerization. With EGCG present in the outer solution of the Aß42-infused membrane, a noteworthy reduction in channel current was observed, suggesting the successful inhibition of oligomerization. This conclusion held true in both, prior and subsequent, stages of oligomerization. Our findings shed light on the toxicity of oligomers, promising invaluable information for future advancements in AD treatment strategies.

7.
J Neurosci Methods ; 409: 110224, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39038715

RESUMEN

BACKGROUND: Chronic compressive myelopathy (CCM) is a major cause of spinal cord disorders in the elderly, in which the spinal cord is compressed by bony or soft tissue structures. Although computed tomography myelography (CTM) has been clinically used for the diagnosis of CCM, a method of CTM in rodents remains to be developed. NEW METHOD: A 50 µl Hamilton syringe attached to a disposable needle was percutaneously inserted into the subarachnoid space (cisterna magna) between the occipital bone and C1 lamina in an anesthetized adult mouse, followed by the injection of contrast medium and CT imaging. RESULTS: CTM clearly visualized the shape of the spinal cord of intact mice and tiptoe-walking Yoshimura (Twy) mice without any health issues. COMPARISON WITH EXISTING METHOD(S): Unlike histology, the current method functions in live mice, directly depicts the compressed spinal cord, and provides clinically related image information. Furthermore, the intrathecal administration of contrast medium through the percutaneous route makes CTM less invasive and takes less time than a conventional intrathecal injection method. CONCLUSIONS: The CTM method used in the present study enables clear visualization of the shape of the dural sac and spinal cord and is useful when conducting experiments on CCM and other spinal diseases in rodents.


Asunto(s)
Medios de Contraste , Inyecciones Espinales , Mielografía , Compresión de la Médula Espinal , Tomografía Computarizada por Rayos X , Animales , Mielografía/métodos , Inyecciones Espinales/métodos , Medios de Contraste/administración & dosificación , Compresión de la Médula Espinal/diagnóstico por imagen , Ratones , Tomografía Computarizada por Rayos X/métodos , Masculino , Médula Cervical/diagnóstico por imagen , Modelos Animales de Enfermedad , Vértebras Cervicales/diagnóstico por imagen
8.
Knee ; 49: 36-44, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38843674

RESUMEN

BACKGROUND: This study investigates the association between additional distal femoral resection and improved flexion contracture in total knee arthroplasty (TKA) with a robot-assisted system. Flexion contracture is a common issue in patients with knee osteoarthritis, which causes postoperative complications and functional limitations. This study aims to evaluate the effectiveness of additional bone resection in flexion contracture correction and knee extension angle improvement after the actual surgical steps. METHODS: The study included 11 patients who underwent posterior-stabilized (PS)-type TKA with a robot-assisted system. The surgical technique consisted of precise bone resection and range of motion evaluation using a navigation system. A precut technique was used to facilitate posterior access and remove osteophytes that cause the contracture. The amount of additional distal femoral resection was determined based on the thickness of the insert trial required for achieving full extension. RESULTS: The flexion contracture correction angle and the amount of additional distal femoral resection demonstrated a linear relationship. An average of 2.0° with the standard error (SE) of 0.6° improvement in flexion contracture was observed per 1.0 mm of additional bone resection. The postoperative evaluation demonstrated a significant improvement in knee extension angle, thereby reducing the contracture degree. CONCLUSION: This study was the first to perform the additional distal femoral resection on the living knee, which closely replicates the actual surgical steps. The current study revealed that an additional 1.0 mm of distal femoral resection in PS-type TKA improves knee extension angle by 2.0° (SE 0.6°) within an additional resection range of 1.0 mm to 3.3 mm.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Fémur , Osteoartritis de la Rodilla , Rango del Movimiento Articular , Procedimientos Quirúrgicos Robotizados , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Artroplastia de Reemplazo de Rodilla/instrumentación , Femenino , Procedimientos Quirúrgicos Robotizados/métodos , Osteoartritis de la Rodilla/cirugía , Masculino , Fémur/cirugía , Anciano , Persona de Mediana Edad , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/fisiopatología , Contractura/cirugía , Resultado del Tratamiento
9.
Am J Sports Med ; 52(9): 2278-2286, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38898822

RESUMEN

BACKGROUND: High tibial osteotomy (HTO) aims to realign the varus knee to alleviate stress in the medial compartment. However, detailed information on the impact of HTO on stress distribution across the tibiofemoral joint surface still needs to be completely elucidated. PURPOSE/HYPOTHESIS: The present study aimed to analyze the subchondral bone density distribution to validate the alignment threshold causing paradoxical changes. We hypothesized that there would be a paradoxical stress change in the medial compartment beyond a specific threshold for lower limb realignment after HTO. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A retrospective clinical study of 32 knees from 30 patients who underwent medial opening-wedge HTO between 2015 and 2019 was conducted at Hokkaido University Hospital. The subchondral bone density across the tibiofemoral joint was analyzed using computed tomography-osteoabsorptiometry before and after HTO. The high-density area (HDA) within the medial and lateral compartments and their subregions, which were quartered in the coronal plane, was specifically examined. RESULTS: The hip-knee-ankle angle, medial proximal tibial angle (MPTA), joint line obliquity (JLO), and joint line convergence angle significantly changed after HTO (P < .01). The HDA of the medial compartment to the total HDA ratio decreased from 83% to 77%. Paradoxically, the HDA in the most central subregion of the medial compartment increased from 24% to 30%. There were significant differences between MPTA and JLO in patients with and without paradoxical changes in the HDA. MPTA and JLO cutoff values causing paradoxical changes in the HDA were 94° and 4°, respectively. CONCLUSION: There was a paradoxical stress increase in the M4 region at the medial compartment associated with the MPTA and JLO beyond specific thresholds. Therefore, surgical planning should be cautiously performed to prevent overcorrection, which can lead to adverse stress distribution changes.


Asunto(s)
Densidad Ósea , Articulación de la Rodilla , Osteotomía , Tibia , Humanos , Osteotomía/métodos , Tibia/cirugía , Tibia/diagnóstico por imagen , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Anciano , Osteoartritis de la Rodilla/cirugía
10.
Anticancer Res ; 44(4): 1591-1601, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38537990

RESUMEN

BACKGROUND/AIM: The purpose of this study was to investigate whether primary tumor resection in patients with bone metastatic breast cancer has an impact on survival using the Surveillance, Epidemiology, and End Results database, considering subtype classification. PATIENTS AND METHODS: We included all female patients with bone metastatic breast cancer at initial presentation between 2010 and 2016 with known hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) statuses. Cases showing unknown cause of death or unknown HR/HER2 status were excluded. Survival analysis was performed using Cox proportional hazards modeling to calculate hazard ratios (HZR). RESULTS: Of the 13,450 patients included in this study, 2,073 patients were HR+/HER2+, 8,597 patients were HR+/HER2-, 797 patients were HR-/HER2+, and 1,182 patients were HR-/HER2- (triple-negative). Five-year overall survival (OS) rate was 34.5% in HR+/HER2+, 26.0% in HR+/HER2-, 29.2% in HR-/HER2+ and 8.0% in triple-negative. Triple-negative patients showed the worsen OS [HR+/HER2+: HZR=2.1, 95% confidence interval (CI)=1.9-2.3; HR+/HER2-: HZR= 2.4, 95%CI=2.2-2.6; HR-/HER2+: HZR=1.5, 95%CI=1.3-1.6]. After excluding patients who died within six months, primary tumor resection prolonged survival in each subtype classification except HR-/HER2+. CONCLUSION: Patients with triple-negative bone metastatic breast cancer showed unfavorable survival. Primary tumor resection prolonged survival in each subtype except for HR-/HER2+.


Asunto(s)
Neoplasias Óseas , Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Pronóstico , Receptor ErbB-2/metabolismo , Análisis de Supervivencia , Modelos de Riesgos Proporcionales , Neoplasias Óseas/metabolismo
11.
Orthop J Sports Med ; 12(4): 23259671241236807, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38571484

RESUMEN

Background: The ideal position of the femoral bone tunnel in the anterior cruciate ligament (ACL) is controversial. The functional importance of the ACL fiber varies depending on where it is attached to the femur. Functionally important fibers can cause high mechanical stress on the bone, and the Wolff law predicts that bone mineral density will increase at high mechanical stress sites. Purpose/Hypothesis: The purpose of this study was to use computed tomography imaging to determine the distribution pattern of bone density in the lateral intercondylar wall. It was hypothesized that the high-density area (HDA) of the lateral intercondylar wall would reflect the functional insertion of the ACL as reported in previous anatomic studies. Study Design: Descriptive epidemiology study. Methods: Data from 39 knees without ACL injuries were retrospectively collected. The HDA of the lateral intercondylar wall was defined as the region containing the top 10% of the radiodensity values. The shape of the HDA was approximated as an ellipse, and the quadrant method was used to determine the center of the ellipse. The association between the ratio of the minor axis to the major axis of the ellipse and background characteristics was investigated. Results: According to the quadrant method, the center of the HDA ellipse was 33.6% in the deep-shallow direction and 23.4% in the high-low direction. The center of the ellipse was comparable to the anatomic center of the ACL footprint, as previously reported. The ratio of the minor axis to the major axis of the ellipse was 0.58 (95% CI, 0.54-0.62). There was a significant negative correlation between the ratio of the minor axis to the major axis of the HDA ellipse and the posterior tibial slope (r = -0.38, P = .02). Conclusion: The center of the HDA ellipse was found to be similar to the anatomic center of the ACL footprint. Considering the mechanical stress responses in bone, the HDA of the lateral intercondylar wall has the potential to represent the ACL insertion, especially functional insertion.

12.
ACS Omega ; 9(15): 17415-17422, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38645345

RESUMEN

Utilizing a binding mode-based physicochemical screening method using d-Ala-d-Ala silica gel, two new macrolactams, named banglactams A (1) and B (2), were discovered from the culture broth of Nonomuraea bangladeshensis K18-0086. In the course of our investigation, we found that d-Ala-d-Ala silica gel precisely differentiated the chemical structures of banglactams and separated them. However, we were not able to obtain enough of 1 to elucidate the structure due to its instability and insolubility. To overcome this challenge, we chemically modified 1 to improve solubility, enabling us to obtain a sufficient material supply for the indirect determination of the structure. Antibacterial activity evaluation of banglactams revealed that 1 binding to d-Ala-d-Ala silica gel exhibited antibacterial activity against Staphylococcus aureus; however, this was not the case with 2. This research indicates the utility of our original binding mode-based PC screening method, and the combination strategy of PC and chemical modifications led us to discover novel antibacterial compounds.

13.
Sci Rep ; 14(1): 8334, 2024 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594295

RESUMEN

Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) is widely used for the detection, diagnosis, and clinical decision-making in oncological diseases. However, in daily medical practice, it is often difficult to make clinical decisions because of physiological FDG uptake or cancers with poor FDG uptake. False negative clinical diagnoses of malignant lesions are critical issues that require attention. In this study, Vision Transformer (ViT) was used to automatically classify 18F-FDG PET/CT slices as benign or malignant. This retrospective study included 18F-FDG PET/CT data of 207 (143 malignant and 64 benign) patients from a medical institute to train and test our models. The ViT model achieved an area under the receiver operating characteristic curve (AUC) of 0.90 [95% CI 0.89, 0.91], which was superior to the baseline Convolutional Neural Network (CNN) models (EfficientNet, 0.87 [95% CI 0.86, 0.88], P < 0.001; DenseNet, 0.87 [95% CI 0.86, 0.88], P < 0.001). Even when FDG uptake was low, ViT produced an AUC of 0.81 [95% CI 0.77, 0.85], which was higher than that of the CNN (DenseNet, 0.65 [95% CI 0.59, 0.70], P < 0.001). We demonstrated the clinical value of ViT by showing its sensitive analysis of easy-to-miss cases of oncological diseases.


Asunto(s)
Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos , Estudios Retrospectivos , Tomografía de Emisión de Positrones/métodos
14.
Sci Rep ; 14(1): 17560, 2024 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080409

RESUMEN

Periodontitis is a prevalent oral inflammatory disease that leads to alveolar bone loss and may exert an adverse impact on systemic health. Periodontal disease may be associated with hepatocellular carcinoma (HCC); however, the mechanism of such an association is unknown. In this study, Stelic Animal model (STAM) mice, a model of nonalcoholic steatohepatitis (NASH)-HCC, were induced to develop periodontitis and subjected to histopathological and immunological analyses. HCC progression was greater in STAM mice with experimental periodontitis compared with that in STAM mice without experimental periodontitis. Tumor necrosis factor-α (TNFα), matrix metalloproteinase-9 (MMP9), collagen 1, and angiopoietin-like protein 2 (ANGPTL2) gene expression was significantly increased in the liver of the periodontitis group. ANGPTL2 was previously reported to be involved in the pathogenesis of periodontitis, and HCC and ANGPTL2 protein tended to be more abundant in the pocket epithelium of STAM mice with experimental periodontitis than in control STAM mice. ANGPTL2 levels in the serum of STAM mice with experimental periodontitis tended to be higher than in control STAM mice. Our results indicate that ANGPTL2 is produced in chronically inflamed periodontal tissue and then travels to the liver via the bloodstream where it accumulates to promote the progression of hepatocellular carcinoma.


Asunto(s)
Carcinoma Hepatocelular , Modelos Animales de Enfermedad , Neoplasias Hepáticas , Periodontitis , Animales , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Periodontitis/patología , Periodontitis/complicaciones , Periodontitis/metabolismo , Ratones , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Proteínas Similares a la Angiopoyetina/metabolismo , Proteínas Similares a la Angiopoyetina/genética , Proteína 2 Similar a la Angiopoyetina , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Hígado/patología , Hígado/metabolismo
15.
Comput Biol Med ; 172: 108197, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38452472

RESUMEN

BACKGROUND: Health-related patient-reported outcomes (HR-PROs) are crucial for assessing the quality of life among individuals experiencing low back pain. However, manual data entry from paper forms, while convenient for patients, imposes a considerable tallying burden on collectors. In this study, we developed a deep learning (DL) model capable of automatically reading these paper forms. METHODS: We employed the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, a globally recognized assessment tool for low back pain. The questionnaire comprised 25 low back pain-related multiple-choice questions and three pain-related visual analog scales (VASs). We collected 1305 forms from an academic medical center as the training set, and 483 forms from a community medical center as the test set. The performance of our DL model for multiple-choice questions was evaluated using accuracy as a categorical classification task. The performance for VASs was evaluated using the correlation coefficient and absolute error as regression tasks. RESULT: In external validation, the mean accuracy of the categorical questions was 0.997. When outputs for categorical questions with low probability (threshold: 0.9996) were excluded, the accuracy reached 1.000 for the remaining 65 % of questions. Regarding the VASs, the average of the correlation coefficients was 0.989, with the mean absolute error being 0.25. CONCLUSION: Our DL model demonstrated remarkable accuracy and correlation coefficients when automatic reading paper-based HR-PROs during external validation.


Asunto(s)
Aprendizaje Profundo , Dolor de la Región Lumbar , Ortopedia , Humanos , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/terapia , Calidad de Vida , Japón , Dolor de Espalda , Encuestas y Cuestionarios
16.
JAC Antimicrob Resist ; 6(4): dlae135, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39165366

RESUMEN

Objectives: Despite the global health risk of carbapenem-resistant Enterobacterales (CRE), especially carbapenemase-producing Enterobacterales (CPE), Japan reports a significantly low frequency of CRE with a predominance of IMP-type carbapenemases. This study aimed to investigate the prevalence and characteristics of CRE isolated from hospitals in the city of Nara, Japan. Methods: We obtained 171 CRE isolates from 16 791 Enterobacterales isolated at 23 hospitals in Nara between January 2018 and December 2021. Isolates of CPE were characterized through antimicrobial susceptibility testing, the carbapenem inactivation method, PCR and DNA sequencing. Genotypic diversity of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae was determined via MLST and PFGE. Results: The prevalence of CRE between 2018 and 2021 was 1.02%, gradually decreasing from 1.13% to 0.74%. Ninety-nine isolates were identified as CPE, representing six species. Ninety-seven CPE isolates harboured bla IMP-6, while the remaining two carried either bla IMP-1 or bla IMP-19. Genotype analysis identified ST131 as the dominant genotype for E. coli, but none for K. pneumoniae. PFGE results suggested clonal spread of CPE in Hospital A, where CRE was isolated in high numbers (n = 44). Conclusions: In this study, CRE prevalence was marginally higher than previously reported in Japan, but still low in frequency. A predominance of Enterobacterales harbouring bla IMP-6 was confirmed in Nara. The spread of CPE at Hospital A suggested the possibility of a nosocomial outbreak due to bla IMP-6 transmission via plasmids or clonal spread. Continued monitoring is crucial for effective management of CRE prevalence in the region.

17.
Sci Rep ; 14(1): 17399, 2024 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-39075117

RESUMEN

Cell-free DNA (cfDNA) is released from injured cells and aggravates inflammation. Patients with coronavirus disease (COVID-19) often develop pneumonia and respiratory failure, and require oxygen therapy (OT), including mechanical ventilation (MV). It remains unclear whether cfDNA predicts the risk of receiving OT or MV in COVID-19 patients. Therefore, we hypothesized that circulating cfDNA levels could reflect the severity of respiratory failure and determine a therapeutic approach for oxygenation in patients with COVID-19. We analyzed cfDNA levels in serum samples from 95 hospitalized patients with COVID-19 at Showa University Hospital (Tokyo, Japan). cfDNA levels were assessed by measuring the copy numbers of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) using quantitative real-time PCR (qPCR). Both cf-nDNA and cf-mtDNA levels were negatively correlated with adjusted SpO2 for FiO2 (SpO2/FiO2 ratio). Elevated cf-nDNA and cf-mtDNA levels were associated with the requirement for OT or MV during patient admission. Multivariate logistic regression analysis revealed that cf-nDNA and cf-mtDNA levels were independent risk factors for OT and MV. These results suggest that both serum cf-nDNA and cf-mtDNA could serve as useful early biomarkers to indicate the necessity of OT or MV in patients with COVID-19.


Asunto(s)
COVID-19 , Ácidos Nucleicos Libres de Células , ADN Mitocondrial , Insuficiencia Respiratoria , Humanos , COVID-19/sangre , COVID-19/complicaciones , COVID-19/virología , Ácidos Nucleicos Libres de Células/sangre , Masculino , Femenino , Anciano , Persona de Mediana Edad , Insuficiencia Respiratoria/sangre , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/virología , ADN Mitocondrial/sangre , SARS-CoV-2/aislamiento & purificación , Biomarcadores/sangre , Respiración Artificial , Anciano de 80 o más Años , Terapia por Inhalación de Oxígeno
18.
Jpn J Radiol ; 42(7): 697-708, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38551771

RESUMEN

PURPOSE: To propose a five-point scale for radiology report importance called Report Importance Category (RIC) and to compare the performance of natural language processing (NLP) algorithms in assessing RIC using head computed tomography (CT) reports written in Japanese. MATERIALS AND METHODS: 3728 Japanese head CT reports performed at Osaka University Hospital in 2020 were included. RIC (category 0: no findings, category 1: minor findings, category 2: routine follow-up, category 3: careful follow-up, and category 4: examination or therapy) was established based not only on patient severity but also on the novelty of the information. The manual assessment of RIC for the reports was performed under the consensus of two out of four neuroradiologists. The performance of four NLP models for classifying RIC was compared using fivefold cross-validation: logistic regression, bidirectional long-short-term memory (BiLSTM), general bidirectional encoder representations of transformers (general BERT), and domain-specific BERT (BERT for medical domain). RESULTS: The proportion of each RIC in the whole data set was 15.0%, 26.7%, 44.2%, 7.7%, and 6.4%, respectively. Domain-specific BERT showed the highest accuracy (0.8434 ± 0.0063) in assessing RIC and significantly higher AUC in categories 1 (0.9813 ± 0.0011), 2 (0.9492 ± 0.0045), 3 (0.9637 ± 0.0050), and 4 (0.9548 ± 0.0074) than the other models (p < .05). Analysis using layer-integrated gradients showed that the domain-specific BERT model could detect important words, such as disease names in reports. CONCLUSIONS: Domain-specific BERT has superiority over the other models in assessing our newly proposed criteria called RIC of head CT radiology reports. The accumulation of similar and further studies of has a potential to contribute to medical safety by preventing missed important findings by clinicians.


Asunto(s)
Procesamiento de Lenguaje Natural , Tomografía Computarizada por Rayos X , Humanos , Tomografía Computarizada por Rayos X/métodos , Japón , Algoritmos , Cabeza/diagnóstico por imagen , Sistemas de Información Radiológica , Femenino , Masculino , Pueblos del Este de Asia
19.
Jpn J Radiol ; 42(6): 590-598, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38413550

RESUMEN

PURPOSE: To predict solid and micropapillary components in lung invasive adenocarcinoma using radiomic analyses based on high-spatial-resolution CT (HSR-CT). MATERIALS AND METHODS: For this retrospective study, 64 patients with lung invasive adenocarcinoma were enrolled. All patients were scanned by HSR-CT with 1024 matrix. A pathologist evaluated subtypes (lepidic, acinar, solid, micropapillary, or others). Total 61 radiomic features in the CT images were calculated using our modified texture analysis software, then filtered and minimized by least absolute shrinkage and selection operator (LASSO) regression to select optimal radiomic features for predicting solid and micropapillary components in lung invasive adenocarcinoma. Final data were obtained by repeating tenfold cross-validation 10 times. Two independent radiologists visually predicted solid or micropapillary components on each image of the 64 nodules with and without using the radiomics results. The quantitative values were analyzed with logistic regression models. The receiver operating characteristic curves were generated to predict of solid and micropapillary components. P values < 0.05 were considered significant. RESULTS: Two features (Coefficient Variation and Entropy) were independent indicators associated with solid and micropapillary components (odds ratio, 30.5 and 11.4; 95% confidence interval, 5.1-180.5 and 1.9-66.6; and P = 0.0002 and 0.0071, respectively). The area under the curve for predicting solid and micropapillary components was 0.902 (95% confidence interval, 0.802 to 0.962). The radiomics results significantly improved the accuracy and specificity of the prediction of the two radiologists. CONCLUSION: Two texture features (Coefficient Variation and Entropy) were significant indicators to predict solid and micropapillary components in lung invasive adenocarcinoma.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Estudios Retrospectivos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Anciano , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/patología , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Invasividad Neoplásica/diagnóstico por imagen , Valor Predictivo de las Pruebas , Anciano de 80 o más Años , Adulto , Pulmón/diagnóstico por imagen , Pulmón/patología , Radiómica
20.
Open Forum Infect Dis ; 10(12): ofad634, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38156045

RESUMEN

Background: The objective of this study was to evaluate the impact of the FilmArray meningitis/encephalitis panel (FAME) on length of stay (LOS) and duration of antimicrobial treatment in children and adults in a Japanese community hospital. Methods: This retrospective cohort study was conducted in Japan between January 2016 and December 2022. We included hospitalized patients with cerebrospinal fluid (CSF) samples and those aged <2 months or who had 5 or more white blood cells/µL in the CSF. To compare the days of therapy (DOT) and LOS between the pre-FAME and FAME periods, multivariate Poisson regression analyses were conducted without an offset term. Results: The number of cases undergoing pathogen-specific polymerase chain reaction increased from 3.7% in the pre-FAME period to 57.5% in the FAME period (P < .001). The pathogen identification rate also increased during the FAME period, from 0.4% to 18.7% (P < .001). While the antibacterial DOT was not statistically different between the 2 periods (adjusted rate ratio [aRR], 1.06 [95% confidence interval {CI}, 1.00-1.13]; P = .063]), the antiviral DOT was significantly shorter in the FAME period (aRR, 0.80 [95% CI, .71-.89]; P < .001). Conclusions: This study revealed a significant reduction in antiviral use during the FAME period, whereas LOS and antibacterial use did not decrease. Given the possibility of factors (eg, the COVID-19 pandemic) affecting the epidemiology of meningitis and encephalitis, the indications and impact of the FAME test should be evaluated with continuous monitoring of the epidemiology of meningitis and encephalitis and its clinical impact.

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