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Podocytes serve as part of the renal filtration unit with slit diaphragms. Although the structure of slit diaphragms between two cells is well characterized, how the tricellular contact of podocytes is organized and how it changes in injured podocytes remains unknown. This study focused on a tricellular junction protein, angulin-3, and its localization in healthy podocytes, in developmental stages, and in pathologic conditions, using a newly established monoclonal antibody. Angulin-3 was confined at tricellular junctions of primordial podocytes, then transiently localized at bicellular junctions as foot process interdigitation developed and the intercellular junctions rearranged into slit diaphragm, and eventually distributed in a sparse punctate pattern on the foot processes of adult podocytes. In the rodent podocyte injury models, angulin-3 showed bicellular localization between the foot processes, and the localization turned from punctate to dashed linear pattern along the effaced foot processes with the progression of podocyte injury. Angulin-3 also accumulated between foot processes in a linear pattern in kidney biopsy samples of human nephrotic syndrome. Additionally, the line length of angulin-3 staining signal correlated with risk of relapse under glucocorticoid therapy in patients with minimal change nephrotic syndrome. This study proposes an image program to score the linearity of the accumulation pattern of angulin-3 to evaluate the relapse risk of patients with minimal change nephrotic syndrome.
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Nefrose Lipoide , Podócitos , Adulto , Humanos , Podócitos/metabolismo , Junções Íntimas/patologia , Nefrose Lipoide/metabolismo , Nefrose Lipoide/patologia , Junções Intercelulares/metabolismo , RecidivaRESUMO
BACKGROUND: Real-time prediction of histologic features of small colorectal polyps may prevent resection and/or pathologic evaluation and therefore decrease colonoscopy costs. Previous studies showed that computer-aided diagnosis (CADx) was highly accurate, though it did not outperform expert endoscopists. OBJECTIVE: To assess the diagnostic performance of histologic predictions by general endoscopists before and after assistance from CADx in a real-life setting. DESIGN: Prospective, multicenter, single-group study. (ClinicalTrials.gov: NCT04437615). SETTING: 6 centers across the United States. PARTICIPANTS: 1252 consecutive patients undergoing colonoscopy and 49 general endoscopists with variable experience in real-time prediction of polyp histologic features. INTERVENTION: Real-time use of CADx during routine colonoscopy. MEASUREMENTS: The primary end points were the sensitivity and specificity of CADx-unassisted and CADx-assisted histologic predictions for adenomas measuring 5 mm or less. For clinical purposes, additional estimates according to location and confidence level were provided. RESULTS: The CADx device made a diagnosis for 2695 polyps measuring 5 mm or less (96%) in 1252 patients. There was no difference in sensitivity between the unassisted and assisted groups (90.7% vs. 90.8%; P = 0.52). Specificity was higher in the CADx-assisted group (59.5% vs. 64.7%; P < 0.001). Among all 2695 polyps measuring 5 mm or less, 88.2% and 86.1% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be resected and discarded without pathologic evaluation. Among 743 rectosigmoid polyps measuring 5 mm or less, 49.5% and 47.9% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be left in situ without resection. LIMITATION: Decision making based on CADx might differ outside a clinical trial. CONCLUSION: CADx assistance did not result in increased sensitivity of optical diagnosis. Despite a slight increase, the specificity of CADx-assisted diagnosis remained suboptimal. PRIMARY FUNDING SOURCE: Olympus America Corporation served as the clinical study sponsor.
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Inteligência Artificial , Pólipos do Colo , Colonoscopia , Diagnóstico por Computador , Sensibilidade e Especificidade , Humanos , Pólipos do Colo/patologia , Estudos Prospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adenoma/patologia , Adenoma/diagnóstico , Neoplasias Colorretais/patologia , Competência Clínica , AdultoRESUMO
BACKGROUND: Recently, intestinal bacteria have attracted attention as factors affecting the prognosis of patients with cancer. However, the intestinal microbiome is composed of several hundred types of bacteria, necessitating the development of an analytical method that can allow the use of this information as a highly accurate biomarker. In this study, we investigated whether the preoperative intestinal bacterial profile in patients with esophageal cancer who underwent surgery after preoperative chemotherapy could be used as a biomarker of postoperative recurrence of esophageal cancer. METHODS: We determined the gut microbiome of the patients using 16S rRNA metagenome sequencing, followed by statistical analysis. Simultaneously, we performed a machine learning analysis using a random forest model with hyperparameter tuning and compared the data obtained. RESULTS: Statistical and machine learning analyses revealed two common bacterial genera, Butyricimonas and Actinomyces, which were abundant in cases with recurrent esophageal cancer. Butyricimonas primarily produces butyrate, whereas Actinomyces are oral bacteria whose function in the gut is unknown. CONCLUSION: Our results indicate that Butyricimonas spp. may be a biomarker of postoperative recurrence of esophageal cancer. Although the extent of the involvement of these bacteria in immune regulation remains unknown, future research should investigate their presence in other pathological conditions. Such research could potentially lead to a better understanding of the immunological impact of these bacteria on patients with cancer and their application as biomarkers.
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Neoplasias Esofágicas , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , RNA Ribossômico 16S/genética , Fezes/microbiologia , Recidiva Local de Neoplasia , Bactérias/genética , Neoplasias Esofágicas/cirurgia , BiomarcadoresRESUMO
Reducing recurrence following radical resection of colon cancer without overtreatment or undertreatment remains a challenge. Postoperative adjuvant chemotherapy (Adj) is currently administered based solely on pathologic TNM stage. However, prognosis can vary significantly among patients with the same disease stage. Therefore, novel classification systems in addition to the TNM are necessary to inform decision-making regarding postoperative treatment strategies, especially stage II and III disease, and minimize overtreatment and undertreatment with Adj. We developed a prognostic prediction system for colorectal cancer using a combined convolutional neural network and support vector machine approach to extract features from hematoxylin and eosin staining images. We combined the TNM and our artificial intelligence (AI)-based classification system into a modified TNM-AI classification system with high discriminative power for recurrence-free survival. Furthermore, the cancer cell population recognized by this system as low risk of recurrence exhibited the mutational signature SBS87 as a genetic phenotype. The novel AI-based classification system developed here is expected to play an important role in prognostic prediction and personalized treatment selection in oncology.
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Asthma is a chronic inflammatory airway disease, in which inflammatory cytokines play a pivotal role. The zinc finger binding protein 36 (ZFP36) family includes ZFP36, ZFP36L1, and ZFP36L2 and is among the RNA-binding proteins (RBPs) reported to cause inflammation. The present study aimed to clarify the roles of the ZFP36 family in asthma, particularly highlighting the relationship between the ZFP36 family and Th2 cells, which are key players in type 2 inflammation in asthma. Real-time PCR analysis revealed the preferential expression of ZFP36 family mRNAs in human white blood cells. Gene expression analysis using public datasets from the GEO database (https://www.ncbi.nlm.nih.gov/gds) showed significantly suppressed expression of ZFP36 family mRNAs in patients with asthma compared to that in healthy controls. Using multiple cytokine assays, Th2 cell transfection with ZFP36 family siRNAs enhanced the expression of inflammatory cytokines IL-8, IFN-γ, CCL3/MIP-1α, CCL4/MIP-1ß, and TNF-α and cell surface molecules CCR4 (CD194) and PSGL-1 (CD162). Treatment with IL-2, 4, and 15 significantly suppressed, and corticosteroid significantly enhanced the expressions of ZFP36 family mRNAs by Th2 cells. In conclusion, the ZFP36 family expressed by Th2 cells was suppressed in patients with asthma, leading to the enhanced expression of cytokines and cell surface molecules. Suppressed ZFP36 expression in asthma may be involved in the enhancement of airway inflammation, and the ZFP36 family may be a therapeutic target for inflammatory diseases, including asthma.
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The chiral recognition of a self-assembled structure of enantiopure (M)-type 2,13-diphenyl[7]thiaheterohelicene ((M)-Ph-[7]TH) was investigated on a Ag(111) substrate by scanning tunnelling microscopy (STM) and tip-enhanced Raman spectroscopy (TERS). In contrast to previous research of thiaheterohelicene and its derivatives showing zigzag row formation on the Ag(111) substrate, the hexagonal ordered structure was observed by STM. The obtained TERS spectra of (M)-Ph-[7]TH were consistent with the Raman spectra calculated on the basis of density functional theory (DFT), which suggests that (M)-Ph-[7]TH was adsorbed on the substrate without decomposition. The sample bias voltage dependence of STM images combined with the calculated molecular orbitals of (M)-Ph-[7]TH indicates that a phenyl ring was observed as a protrusion at +3.0 V, whereas the helicene backbone was observed at +0.5 V. From these results, a possible model of the hexagonal structure was proposed. Owing to the phenyl ring, the van der Waals interaction between (M)-Ph-[7]TH and the substrate becomes strong. This leads to the formation of the hexagonal structure with the same symmetry as the substrate.
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INTRODUCTION: The traditional Japanese herbal medicine hochuekkito (TJ-41) has been reported to ameliorate systemic inflammation and malnutrition in patients with chronic obstructive pulmonary disease (COPD). TJ-41 has also been known to have preventive effects against influenza virus infection. However, its role in the acute exacerbation of COPD (AECOPD) remains to be elucidated. Our previous study established a murine model of viral infection-associated AECOPD that was induced by intratracheal administration of porcine pancreatic elastase (PPE) and polyinosinic-polycytidylic acid [poly(I:C)]. Here, we used this model and investigated the effects of TJ-41 in AECOPD. METHODS: Specific pathogen-free C57BL/6J mice were used. A COPD model was induced by treating mice intratracheally with PPE on day 0. To generate the murine model of AECOPD, poly(I:C) was administered intratracheally following PPE treatment on days 22-24. Mice were sacrificed and analyzed on day 25. Mice were fed a diet containing 2% TJ-41 or a control diet. RESULTS: Daily oral intake of TJ-41 significantly decreased the numbers of neutrophils and lymphocytes in the bronchoalveolar lavage fluid (BALF), which was accompanied by decreased transcripts of CXC chemokines involved in neutrophil migration, viz., Cxcl1 and Cxcl2, in whole lung homogenates and reduced Cxcl2 concentration in BALF. CONCLUSION: This study demonstrates the anti-inflammatory effects of TJ-41 in a mouse model of AECOPD, suggesting the effectiveness of TJ-41 for the management of COPD. Clinical investigations evaluating the therapeutic efficacy of TJ-41 in AECOPD would be meaningful.
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Medicamentos de Ervas Chinesas , Doença Pulmonar Obstrutiva Crônica , Humanos , Camundongos , Animais , Suínos , Modelos Animais de Doenças , Japão , Camundongos Endogâmicos C57BL , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/complicações , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêuticoRESUMO
BACKGROUND: Direct surgery is an important option to treat vertebral artery (VA) stenosis. METHOD: A patient with symptomatic stenosis at the origin of the right VA underwent transposition of the right VA to the common carotid artery (CCA). Using the sternocleidomastoid sparing approach, the VA was anastomosed to the posterior wall of the CCA by twisting the CCA to expose its posterior wall to face the operative field. CONCLUSION: This approach, consisting of securing the proximal VA and then following it to its distal end, not only preserves the sternocleidomastoid muscle but also protects the sympathetic chains and thoracic duct.
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Artéria Carótida Primitiva , Artéria Vertebral , Humanos , Artéria Carótida Primitiva/cirurgia , Artéria Vertebral/cirurgia , Artéria Vertebral/diagnóstico por imagem , Insuficiência Vertebrobasilar/cirurgia , Insuficiência Vertebrobasilar/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Músculos do Pescoço/cirurgia , Resultado do TratamentoRESUMO
PURPOSE: This study aimed to assess the efficiency of artificial intelligence (AI) in the detection of visceral pleural invasion (VPI) of lung cancer using high-resolution computed tomography (HRCT) images, which is challenging for experts because of its significance in T-classification and lymph node metastasis prediction. METHODS: This retrospective analysis was conducted on preoperative HRCT images of 472 patients with stage I non-small cell lung cancer (NSCLC), focusing on lesions adjacent to the pleura to predict VPI. YOLOv4.0 was utilized for tumor localization, and EfficientNetv2 was applied for VPI prediction with HRCT images meticulously annotated for AI model training and validation. RESULTS: Of the 472 lung cancer cases (500 CT images) studied, the AI algorithm successfully identified tumors, with YOLOv4.0 accurately localizing tumors in 98% of the test images. In the EfficientNet v2-M analysis, the receiver operating characteristic curve exhibited an area under the curve of 0.78. It demonstrated powerful diagnostic performance with a sensitivity, specificity, and precision of 76.4% in VPI prediction. CONCLUSION: AI is a promising tool for improving the diagnostic accuracy of VPI for NSCLC. Furthermore, incorporating AI into the diagnostic workflow is advocated because of its potential to improve the accuracy of preoperative diagnosis and patient outcomes in NSCLC.
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BACKGROUND: The forearm flexor-pronator muscles act as a dynamic elbow stabilizer against elbow valgus load during baseball pitching. The elasticity of these muscles increases with pitching. However, it is unclear whether increased muscle elasticity is associated with greater elbow valgus torque during pitching. This study aimed to determine the relationship between the elasticity of the forearm flexor-pronator muscles and elbow valgus torque during pitching in young baseball pitchers. METHODS: We recruited 124 young baseball pitchers aged 9 to 12 years. The exclusion criteria included current pain with pitching, history of surgery on the tested extremity, or injuries on the tested extremity within the past 12 months. Before the examination, participants completed a questionnaire about their age, height, weight, dominant arm and practice time per week. The strain ratios of flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), and pronator teres as the index of muscle elasticity were measured using ultrasound strain elastography. Participants pitched three fastballs at a distance of 52 ft 6 in (16 m) with maximum effort while wearing a sensor sleeve that recorded the elbow valgus torque. A multiple linear regression analysis was conducted to examine the association between muscle elasticity and elbow valgus torque, adjusting for age, height, weight, and practice time. RESULTS: The final analysis included 107 pitchers. After adjusting for covariates, increased strain ratio of the FCU was significantly associated with greater elbow valgus torque (coefficients = 0.038, 95% confidence interval [CI], 0.016-0.059, P<.001). Similarly, increased strain ratio of the FDS was significantly associated with greater elbow valgus torque (coefficients = 0.027, 95% CI, 0.013-0.042, P<.001). CONCLUSION: The high elasticities of the FCU and FDS were associated with greater elbow valgus torque during pitching in young baseball pitchers. The high elasticity of these muscles is a protective response and may be necessary for young baseball pitchers with greater elbow valgus torque during pitching. Among young baseball pitchers with greater elbow valgus torque, those who are unable to produce the higher elasticities of these muscles could have greater elbow valgus load during pitching and be at a higher risk for elbow injuries. The measurement of the elasticities of the FCU and FDS may be useful for identifying young baseball pitchers at risk of sustaining elbow injuries.
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Esotropia and exotropia in the entity of comitant strabismus are multifactorial diseases with both genetic and environmental backgrounds. Idiopathic superior oblique muscle palsy, as the predominant entity of non-comitant (paralytic) strabismus, also has a genetic background, as evidenced by varying degrees of muscle hypoplasia. A genome-wide association study (GWAS) was conducted of 711 Japanese patients with esotropia (n= 253), exotropia (n = 356), and idiopathic superior oblique muscle palsy (n = 102). The genotypes of single nucleotide polymorphisms (SNPs) were determined by Infinium Asian Screening Array. Three control cohorts from the Japanese population were used: two cohorts from BioBank Japan (BBJ) and the Nagahama Cohort. BBJ (180K) was genotyped by a different array, Illumina Infinium OmniExpressExome or HumanOmniExpress, while BBJ (ASA) and the Nagahama Cohort were genotyped by the same Asian array. After quality control of SNPs and individuals, common SNPs between the case cohort and the control cohort were chosen in the condition of genotyping by different arrays, while all SNPs genotyped by the same array were used for SNP imputation. The SNPs imputed with R-square values ≥ 0.3 were used to compare the case cohort of each entity or the combined entity with the control cohort. In comparison with BBJ (180K), the esotropia group and the exotropia group showed CDCA7 and HLA-F, respectively, as candidate genes at a significant level of p < 5 × 10-8, while the idiopathic superior oblique muscle palsy group showed DAB1 as a candidate gene which is involved in neuronal migration. DAB1 was also detected as a candidate in comparison with BBJ (ASA) and the Nagahama Cohort at a weak level of significance of p < 1 × 10-6. In comparison with BBJ (180K), RARB (retinoic acid receptor-ß) was detected as a candidate at a significant level of p < 5 × 10-8 in the combined group of esotropia, exotropia, and idiopathic superior oblique muscle palsy. In conclusion, a series of GWASs with three different control cohorts would be an effective method with which to search for candidate genes for multifactorial diseases such as strabismus.
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Esotropia , Exotropia , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Humanos , Estudos de Casos e Controles , Estudos de Coortes , População do Leste Asiático/genética , Esotropia/genética , Exotropia/genética , Predisposição Genética para Doença , Genótipo , JapãoRESUMO
Neuroendocrine carcinoma (NEC) is a highly aggressive subtype of the neuroendocrine tumor with an extremely poor prognosis. We have previously conducted a comprehensive genomic analysis of over 100 cases of NEC of the gastrointestinal system (GIS-NEC) and unraveled its unique and organ-specific genomic drivers. However, the epigenomic features of GIS-NEC remain unexplored. In this study, we have described the epigenomic landscape of GIS-NEC and small cell lung carcinoma (SCLC) by integrating motif enrichment analysis from the assay of transposase-accessible chromatin sequencing (ATAC-seq) and enhancer profiling from a novel cleavage under targets and tagmentation (CUT&Tag) assay for H3K27ac and identified ELF3 as one of the super-enhancer-related transcriptional factors in NEC. By combining CUT&Tag and knockdown RNA sequencing for ELF3, we uncovered the transcriptional network regulated by ELF3 and defined its distinctive gene signature, including AURKA, CDC25B, CLDN4, ITGB6, and YWAHB. Furthermore, a loss-of-function assay revealed that ELF3 depletion led to poor cell viability. Finally, using gene expression of clinical samples, we successfully divided GIS-NEC patients into two subgroups according to the ELF3 signature and demonstrated that tumor-promoting pathways were activated in the ELF3 signature-high group. Our findings highlight the transcriptional regulation of ELF3 as an oncogenic transcription factor and its tumor-promoting properties in NEC.
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Carcinoma Neuroendócrino , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Epigenômica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma Neuroendócrino/genética , Neoplasias Pulmonares/patologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas Proto-Oncogênicas c-ets/genéticaRESUMO
AIM: Developing effective adjuvant therapies is essential for improving the surgical outcomes in patients with hepatocellular carcinoma (HCC). Immunotherapy against HCC has become a promising strategy; however, only approximately 30% of all HCC patients respond to immunotherapy. Previously, we generated the novel therapeutic vaccine comprising multi-human leukocyte antigen-binding heat shock protein 70/glypican-3 peptides with a novel adjuvant combination of hLAG-3Ig and poly-ICLC. We also confirmed the safety of this vaccination therapy, as well as its capacity for the effective induction of immune responses in a previous clinical trial. METHODS: In this phase I study, we administered this vaccine intradermally six times before surgery, and 10 times after surgery to patients with untreated, surgically resectable HCC (stage II to IVa). The primary end-points of this study were the safety and feasibility of this treatment. We also analyzed the resected tumor specimens pathologically using hematoxylin-eosin staining and immunohistochemistry for heat shock protein 70, glypican 3, CD8 and programmed death-1. RESULTS: A total of 20 human leukocyte antigen-matched patients received this vaccination therapy with an acceptable side-effect profile. All patients underwent planned surgery without vaccination-related delay. Immunohistochemical analyses revealed that potent infiltration of CD8+ T cells into tumors with target antigen expression was observed in 12 of 20 (60%) patients. CONCLUSIONS: This novel therapeutic vaccine was safe as perioperative immunotherapy for patients with HCC, and has the potential to strongly induce CD8+ T cells infiltration into tumors.
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PURPOSE: Electromyostimulation (EMS) induces a short-term change in muscle metabolism, and EMS training induces long-term improvements of muscle atrophy and function. However, the effects of EMS training on intramuscular fat in older adults are still poorly known. The purpose of this study was to examine whether the intramuscular fat index and biochemical parameters change with EMS training of the quadriceps femoris muscles in older adults. METHODS: Nineteen non-obese older men and women performed EMS training of the quadriceps femoris for 12 weeks (3 times/week; single session for 30 min). The intramuscular fat content index was estimated by echo intensity of the vastus lateralis and rectus femoris muscles on ultrasonography, and muscle thickness was also measured. Muscle strength was assessed as the maximal voluntary contraction during isometric knee extension. Echo intensity, muscle thickness, and muscle strength were measured before and after EMS training. A rested/fasting blood samples were collected before and after EMS training for measuring plasma glucose, insulin, free fatty acid, triglyceride, and interleukin-6 concentrations. To examine the acute effect of a single-EMS session on biochemical parameters, blood samples were taken before and after the EMS session. RESULTS: EMS training did not significantly change echo intensity in muscles, muscle thickness, muscle strength, or biochemical parameters. Regarding the acute effect on blood lipid concentrations, a single-EMS session increased free fatty acid and glucose concentrations. CONCLUSION: EMS sessions had an acute effect of increasing free fatty acid and glucose concentrations, but EMS training intervention did not improve intramuscular fat content.
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Terapia por Estimulação Elétrica , Ácidos Graxos não Esterificados , Masculino , Humanos , Feminino , Idoso , Força Muscular , Músculo Quadríceps/diagnóstico por imagem , Músculo Quadríceps/fisiologia , Ultrassonografia , Glucose , Músculo Esquelético/fisiologiaRESUMO
PURPOSE: This study compared medial elbow torque in youth baseball pitchers with and without a history of medial elbow injuries to determine the relationship between medial elbow torque during pitching and having a history of medial elbow injuries. METHODS: We recruited 171 youth baseball pitchers aged 9 to 12 years old. The exclusion criteria included current pain with pitching, history of surgery on the tested extremity, or osteochondritis dissecans of the humeral capitellum. The participants were grouped into 3 groups: injury <1-year, injury >1-year, and control, based on ultrasonographic abnormalities of the elbow and the presence of elbow pain. Pitchers pitched 3 fastballs while wearing a sensor sleeve that recorded the medial elbow torque, arm speed, and shoulder rotation. Ball velocity was measured using a radar gun. RESULTS: The final analysis included 164 pitchers. Thirty were assigned to the injury <1-year group, 34 to the injury >1-year group, and 100 to the control group. The medial elbow torque was significantly greater in the injury <1-year group compared with the control group (18.6 ± 3.6 Nm vs 16.2 ± 4.8 Nm, P = .023). A multiple regression analysis revealed that ball velocity (B = 0.282, P < .001) and body weight (B = -0.224, P < .001) were significantly associated with medial elbow torque, but not with the history of medial elbow injuries. CONCLUSIONS: Increased medial elbow torque was associated with greater ball velocity regardless of the history of medial elbow injuries. Youth baseball pitchers with a history of medial elbow injuries within one year had greater medial elbow torque during pitching; however, having a history of medial elbow injuries was not an independent factor in increasing medial elbow torque. Limiting the ball velocity can reduce medial elbow torque and may prevent elbow injuries in youth baseball pitchers. LEVEL OF EVIDENCE: Level II, prospective comparative prognostic investigation with the patients enrolled at different time point.
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Beisebol , Articulação do Cotovelo , Humanos , Adolescente , Criança , Cotovelo , Beisebol/lesões , Torque , Estudos Prospectivos , Fenômenos BiomecânicosRESUMO
Early mobilization and rehabilitation therapy are becoming more critical in acute stroke, traumatic brain injury, and neurological disorder. Better functional prognosis for patients are obtained by performing comprehensive early mobilization and rehabilitation by a multidisciplinary team, generally within 48 hours after the onset. Early and frequent mobilization and rehabilitation therapy are recommended unless systemic management is paramount, such as hemodynamic instability, increased intracranial pressure, or active bleeding. Future considerations to be verified include implementation of rehabilitation in the very early phase(e.g., within 24 hours after the onset), selection of patients(e.g., when to start rehabilitation for each disease type), amount of exercise load in the intensive care unit(ICU), and content of training at the early stage. In addition, there are still few established methods for evaluating motor activity that can be performed in bed. It is also necessary to consider the nature of the rehabilitation team and leadership that were poorly addressed.
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Lesões Encefálicas Traumáticas , Hipertensão Intracraniana , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Unidades de Terapia IntensivaRESUMO
BACKGROUND: Effects of a multicomponent exercise programme have an impact on the physical, cognitive, and psychological domains in elderly community-dwellers. However, some individuals aged 65 years or more have not shown positive effects after the intervention as reported in similar research. The objective of this quasi-experimental study was to clarify the effectiveness of a multicomponent programme based on reality orientation therapy (ROT) on the physical performance, cognitive ability, and psychological state in the elderly. METHOD: Participants were recruited from the general public in 20 areas of Akita Prefecture, Japan, and they took part in each exercise programme for 90 min a day, once every 2 weeks, for 3 months, according to the group classification using cluster randomization into 20 cohorts in Akita. Physical, cognitive, and geriatric depression assessments were performed at baseline and after the 3-month intervention in both the ROT-based intervention group and the control group. RESULT: The final samples for analysis consisted of 31 participants in the control group and 30 participants in the intervention group. The results of the statistical analysis comparing the two groups showed that the 5-repetition sit-to-stand test was performed significantly faster (P < 0.05) and that the results of the word list memory (WM) test and the Symbol Digit Substitution Task also had significantly improved (P < 0.05) after the intervention in both groups. The WM score did not show an interactive effect between the group and time factors, but it had a significant main effect on time in both groups (P < 0.05). CONCLUSION: The results of our quasi-experimental study indicated that the multicomponent programme based on the ROT would be as effective as the original multicomponent programme combined with aerobic exercise and cognitive tasks, as highlighted in the WM.
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Cognição , Exercício Físico , Idoso , Humanos , Terapia por Exercício/métodos , Avaliação Geriátrica , Memória , Desempenho Físico FuncionalRESUMO
Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor with dismal prognosis. Recently, molecular subtypes of SCLC have been defined by the expression status of ASCL1, NEUROD1, YAP1, and POU2F3 transcription regulators. ASCL1 is essential for neuroendocrine differentiation and is expressed in the majority of SCLC. Although previous studies investigated ASCL1 target genes in SCLC cells, ASCL1-mediated regulation of miRNAs and its relationship to molecular subtypes remain poorly explored. Here, we performed genome-wide profiling of chromatin modifications (H3K27me3, H3K4me3, and H3K27ac) by CUT&Tag assay and ASCL1 knockdown followed by RNA sequencing and miRNA array analyses in SCLC cells. ASCL1 could preferentially regulate genes associated with super-enhancers (SEs) defined by enrichment of H3K27ac marking. Moreover, ASCL1 positively regulated several SE-associated miRNAs, such as miR-7, miR-375, miR-200b-3p, and miR-429, leading to repression of their targets, whereas ASCL1 suppressed miR-455-3p, an abundant miRNA in other molecular subtypes. We further elucidated unique patterns of SE-associated miRNAs in different SCLC molecular subtypes, highlighting subtype-specific miRNA networks with functional relevance. Notably, we found apparent de-repression of common target genes of different miRNAs following ASCL1 knockdown, suggesting combinatorial action of multiple miRNAs underlying molecular heterogeneity of SCLC (e.g., co-targeting of YAP1 by miR-9 and miR-375). Our comprehensive analyses provide novel insights into SCLC pathogenesis and a clue to understanding subtype-dependent phenotypic differences.
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Neoplasias Pulmonares , MicroRNAs , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/metabolismo , Neoplasias Pulmonares/patologia , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismoRESUMO
Non-muscle invasive bladder cancer (NMIBC) generally has a good prognosis; however, recurrence after transurethral resection (TUR), the standard primary treatment, is a major problem. Clinical management after TUR has been based on risk classification using clinicopathological factors, but these classifications are not complete. In this study, we attempted to predict early recurrence of NMIBC based on machine learning of quantitative morphological features. In general, structural, cellular, and nuclear atypia are evaluated to determine cancer atypia. However, since it is difficult to accurately quantify structural atypia from TUR specimens, in this study, we used only nuclear atypia and analyzed it using feature extraction followed by classification using Support Vector Machine and Random Forest machine learning algorithms. For the analysis, 125 patients diagnosed with NMIBC were used; data from 95 patients were randomly selected for the training set, and data from 30 patients were randomly selected for the test set. The results showed that the support vector machine-based model predicted recurrence within 2 years after TUR with a probability of 90% and the random forest-based model with probability of 86.7%. In the future, the system can be used to objectively predict NMIBC recurrence after TUR.
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Neoplasias da Bexiga Urinária , Humanos , Aprendizado de Máquina , Invasividade Neoplásica , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
INTRODUCTION: Psychological disorders, such as depression, are markedly prevalent in patients with airway diseases. In this study, we assessed the effect of treatment with dupilumab, an IL-4 receptor α chain antibody, on depressive symptoms in a cohort of patients with asthma with eosinophilic chronic rhinosinusitis (ECRS). METHODS: The study participants, diagnosed with asthma and ECRS, were assessed for symptoms and quality of life (QOL) scores for asthma and ECRS and medications. The Patient Health Questionnaire-9 (PHQ-9) scores were used to evaluate the depressive state. The depressive symptoms were compared with asthma and ECRS symptoms both at the time of initiation and after 4 months of dupilumab treatment. RESULTS: Ultimately, 31 patients were included in the study. Most patients demonstrated a depressive state that was correlated with the nasal symptom score. In the evaluation 4 months after dupilumab treatment, the PHQ-9 score was significantly reduced, and the decrease was remarkable in patients whose nasal symptom score was reduced by 50% or more. Additionally, the PHQ-9 scores in patients with improved nasal and asthma symptoms were significantly reduced. DISCUSSION/CONCLUSION: Dupilumab may improve QOL in patients with bronchial asthma with ECRS by reducing depressive symptoms through the improvement of clinical symptoms.