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1.
Proc Mach Learn Res ; 227: 1406-1422, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38993526

RESUMEN

Multiplex immunofluorescence (MxIF) is an advanced molecular imaging technique that can simultaneously provide biologists with multiple (i.e., more than 20) molecular markers on a single histological tissue section. Unfortunately, due to imaging restrictions, the more routinely used hematoxylin and eosin (H&E) stain is typically unavailable with MxIF on the same tissue section. As biological H&E staining is not feasible, previous efforts have been made to obtain H&E whole slide image (WSI) from MxIF via deep learning empowered virtual staining. However, the tiling effect is a long-lasting problem in high-resolution WSI-wise synthesis. The MxIF to H&E synthesis is no exception. Limited by computational resources, the cross-stain image synthesis is typically performed at the patch-level. Thus, discontinuous intensities might be visually identified along with the patch boundaries assembling all individual patches back to a WSI. In this work, we propose a deep learning based unpaired high-resolution image synthesis method to obtain virtual H&E WSIs from MxIF WSIs (each with 27 markers/stains) with reduced tiling effects. Briefly, we first extend the CycleGAN framework by adding simultaneous nuclei and mucin segmentation supervision as spatial constraints. Then, we introduce a random walk sliding window shifting strategy during the optimized inference stage, to alleviate the tiling effects. The validation results show that our spatially constrained synthesis method achieves a 56% performance gain for the downstream cell segmentation task. The proposed inference method reduces the tiling effects by using 50% fewer computation resources without compromising performance. The proposed random sliding window inference method is a plug-and-play module, which can be generalized for other high-resolution WSI image synthesis applications. The source code with our proposed model are available at https://github.com/MASILab/RandomWalkSlidingWindow.git.

2.
Microbiol Resour Announc ; : e0045924, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967471

RESUMEN

Here, we present the draft genome of Bacillus proteolyticus IMGN4, the gram-positive, soil-dwelling bacterium discovered in mountain Maemi, Republic of Korea in May 2019. The assembly resulted in 7 contigs, comprising a total of 6,063,502 base pairs and have 6,115 coding sequences.

3.
Medicine (Baltimore) ; 103(28): e38941, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38996151

RESUMEN

Recently, interest in sarcopenia has been increasing in patients with various neurological diseases. Thus, we investigated the presence of sarcopenia in patients with episodic migraine (EM) based on temporal muscle thickness (TMT). This was a retrospectively observational study following STROBE guidelines. We enrolled patients with EM and healthy controls. Both groups underwent brain magnetic resonance imaging, including three-dimensional T1-weighted imaging. We calculated the TMT using T1-weighted imaging, which is a marker for sarcopenia. We compared TMT between patients with EM and healthy controls, and analyzed it according to presence of migraine aura. We retrospectively enrolled 82 patients with EM and 53 healthy controls. TMT was not different between patients with EM and healthy controls (10.804 ±â€…2.045 mm in patients with EM vs 10.721 ±â€…1.547 mm in healthy controls, P = .801). Furthermore, TMT was not different according to presence of migraine aura in patients with EM (10.994 ±â€…2.016 mm in patients with migraine aura vs 10.716 ±â€…2.071 mm in those without, P = .569). There were no correlations between TMT and clinical characteristics in patients with EM, including age, age of onset, duration of migraine, headache intensity, and headache frequency. This study found no statistical difference in TMT between patients with EM and healthy controls or between patients with EM with and without aura. These findings suggest that there is no evidence of sarcopenia in patients with EM.


Asunto(s)
Imagen por Resonancia Magnética , Trastornos Migrañosos , Sarcopenia , Humanos , Estudios Retrospectivos , Sarcopenia/epidemiología , Sarcopenia/diagnóstico por imagen , Sarcopenia/etiología , Masculino , Femenino , Adulto , Trastornos Migrañosos/diagnóstico por imagen , Persona de Mediana Edad , Músculo Temporal/diagnóstico por imagen , Estudios de Casos y Controles , Migraña con Aura
4.
Neurospine ; 21(2): 565-574, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38955529

RESUMEN

OBJECTIVE: To evaluate C2 muscle preservation effect and the radiological and clinical outcomes after C2 recapping laminoplasty. METHODS: Fourteen consecutive patients who underwent C2 recapping laminoplasty around C1-2 level were enrolled. To evaluate muscle preservation effect, the authors conducted a morphological measurement of extensor muscles between the operated and nonoperated side. Two surgeons measured the cross-sectional area (CSA) of obliquus capitis inferior (OCI) and semispinalis cervicis (SSC) muscle before and after surgery to determine atrophy rates (ARs). Additionally, we examined range of motion (ROM), sagittal vertical axis (SVA), neck visual analogue scale (VAS), Neck Disability Index (NDI), and Japanese Orthopaedic Association (JOA) score to assess potential changes in alignment and consequent clinical outcomes following posterior cervical surgery. RESULTS: We measured the CSA of OCI and SSC before surgery, and at 6 and 12 months postoperatively. Based on these measurements, the AR of the nonoperated SSC was 0.1% ± 8.5%, the AR of the operated OCI was 2.0% ± 7.2%, and the AR of the nonoperated OCI was -0.7% ± 5.1% at the 12 months after surgery. However, the AR of the operated side's SSC was 11.2% ± 12.5%, which is a relatively higher value than other measurements. Despite the atrophic change of SSC on the operated side, there were no prominent changes observed in SVA, C0-2 ROM, and C2-7 ROM between preoperative and 12 months postoperative measurements, which were 11.8 ± 10.9 mm, 16.3° ± 5.9°, and 48.7° ± 7.7° preoperatively, and 14.1 ± 11.6 mm, 16.1° ± 7.2°, and 44.0° ± 10.3° at 12 months postoperative, respectively. Improvement was also noted in VAS, NDI, and JOA scores after surgery with JOA recovery rate of 77.3% ± 29.6%. CONCLUSION: C2 recapping laminoplasty could be a useful tool for addressing pathologies around the upper cervical spine, potentially mitigating muscle atrophy and reducing postoperative neck pain, while maintaining sagittal alignment and ROM.

5.
Cancer Imaging ; 24(1): 84, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965621

RESUMEN

BACKGROUND: This study aimed to quantitatively reveal contributing factors to airway navigation failure during radial probe endobronchial ultrasound (R-EBUS) by using geometric analysis in a three-dimensional (3D) space and to investigate the clinical feasibility of prediction models for airway navigation failure. METHODS: We retrospectively reviewed patients who underwent R-EBUS between January 2017 and December 2018. Geometric quantification was analyzed using in-house software built with open-source python libraries including the Vascular Modeling Toolkit ( http://www.vmtk.org ), simple insight toolkit ( https://sitk.org ), and sci-kit image ( https://scikit-image.org ). We used a machine learning-based approach to explore the utility of these significant factors. RESULTS: Of the 491 patients who were eligible for analysis (mean age, 65 years +/- 11 [standard deviation]; 274 men), the target lesion was reached in 434 and was not reached in 57. Twenty-seven patients in the failure group were matched with 27 patients in the success group based on propensity scores. Bifurcation angle at the target branch, the least diameter of the last section, and the curvature of the last section are the most significant and stable factors for airway navigation failure. The support vector machine can predict airway navigation failure with an average area under the curve of 0.803. CONCLUSIONS: Geometric analysis in 3D space revealed that a large bifurcation angle and a narrow and tortuous structure of the closest bronchus from the lesion are associated with airway navigation failure during R-EBUS. The models developed using quantitative computer tomography scan imaging show the potential to predict airway navigation failure.


Asunto(s)
Imagenología Tridimensional , Neoplasias Pulmonares , Humanos , Masculino , Femenino , Anciano , Estudios Retrospectivos , Imagenología Tridimensional/métodos , Persona de Mediana Edad , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Broncoscopía/métodos , Endosonografía/métodos , Aprendizaje Automático
6.
Gastric Cancer ; 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970748

RESUMEN

BACKGROUND: Changes in gastric microbiome are associated with gastric carcinogenesis. Studies on the association between gastric mucosa-associated gastric microbiome (MAM) and metachronous gastric cancer are limited. This study aimed to identify gastric MAM as a predictive factor for metachronous recurrence following endoscopic resection of gastric neoplasms. METHOD: Microbiome analyses were conducted for 81 patients in a prospective cohort to investigate surrogate markers to predict metachronous recurrence. Gastric MAM in non-cancerous corporal biopsy specimens was evaluated using Illumina MiSeq platform targeting 16S ribosomal DNA. RESULTS: Over a median follow-up duration of 53.8 months, 16 metachronous gastric neoplasms developed. Baseline gastric MAM varied with Helicobacter pylori infection status, but was unaffected by initial pathologic diagnosis, presence of atrophic gastritis, intestinal metaplasia, or synchronous lesions. The group with metachronous recurrence did not exhibit distinct phylogenetic diversity compared with the group devoid of recurrence but showed significant difference in ß-diversity. The study population could be classified into two distinct gastrotypes based on baseline gastric MAM: gastrotype 1, Helicobacter-abundant; gastrotype 2: Akkermansia-abundant. Patients in gastrotype 2 showed higher risk of metachronous recurrence than gastrotype (Cox proportional hazard analysis, adjusted hazard ratio [95% confidence interval]: 5.10 [1.09-23.79]). CONCLUSIONS: Gastric cancer patients can be classified into two distinct gastrotype groups by their MAM profiles, which were associated with different risk of metachronous recurrence.

7.
J Thorac Oncol ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38992468

RESUMEN

PURPOSE: The use of tumor-informed circulating tumor DNA (ctDNA) testing in early-stage patients before surgery is limited mainly due to restricted tissue access and extended turnaround times. This study aimed to evaluate the clinical value of a tumor-naïve, methylation-based cell-free DNA assay in a large cohort of patients with resected non-small cell lung cancer (NSCLC). METHOD: We analyzed pre-surgical plasma samples from 895 patients with EGFR and ALK-wild-type, clinical stage I or II NSCLC. The ctDNA status was evaluated for its prognostic significance in relation to tumor volume, metabolic activity, histology, histological subtypes, and clinical-to-pathological TNM upstaging. RESULTS: Pre-surgical ctDNA detection was observed in 55 out of 414 (13%) patients with clinical stage I lung adenocarcinoma (LUAD) and was associated with poor recurrence-free survival (RFS) (2-year RFS 69% versus 91%; log-rank P<0.001), approaching that of clinical stage II LUAD. Pre-surgical ctDNA detection was not prognostic in patients with clinical stage II LUAD or non-LUAD. Within LUAD, tumor volume and positron emission tomography avidity interacted to predict pre-surgical ctDNA detection. Moreover, pre-surgical ctDNA detection was predictive of the post-surgical discovery of IASLC G3 tumors (P<0.001) and pathological TNM upstaging (P<0.001). Notably, pre-surgical ctDNA detection strongly correlated with higher PD-L1 expression in tumors (positive rates 28% vs. 55%, P<0.001), identifying a subgroup likely to benefit from anti-PD-(L)-1 therapies. CONCLUSION: These findings support the integration of ctDNA testing into routine diagnostic workflows in early-stage NSCLC without the need of tumor tissue profiling. Furthermore, it is clinically useful in identifying high-risk patients who might benefit from innovative treatments, including neoadjuvant immune checkpoint inhibitors.

8.
JHEP Rep ; 6(7): 101099, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38974366

RESUMEN

Background & Aims: Combined 18F-fluorodeoxyglucose (FDG) and 11C-acetate (dual-tracer) positron-emission tomography/computed tomography (PET/CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels. Methods: We retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020. For staging, we recorded new lesion detection rates, changes in the Barcelona Clinic Liver Cancer (BCLC) classification, and treatment allocation due to dual-tracer PET/CT. To characterize indeterminate lesions and unexplained elevation of serum AFP levels, the sensitivity and specificity of dual-tracer PET/CT in diagnosing HCC were evaluated. A multidisciplinary external review and a cost-benefit analysis of patients for metastatic screening were also performed. Results: Dual-tracer PET/CT identified new lesions in 14.3% of 273 staging patients, resulting in BCLC upstaging in 11.7% and treatment modifications in 7.7%. It upstaged 8.1% of 260 patients undergoing metastatic screening, with estimated savings of US$495 per patient. It had a sensitivity and specificity of 80.7% (95% CI 71.2-88.6%) and 94.8% (95% CI 90.4-98.6%), respectively, for diagnosing HCC in 201 indeterminate lesions. It detected HCC in 45.1% of 51 patients with unexplained elevations in serum AFP concentrations. External review revealed substantial agreement between local and external image interpretation and patient assessment (n = 273, κ = 0.822; 95% CI 0.803-0.864). Conclusions: Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP. Impact and implications: Compared to CT or MRI, dual-tracer positron-emission tomography/computed tomography (PET/CT) led to upstaging in 12% of patients with hepatocellular carcinoma (HCC) undergoing staging, resulting in treatment modification in 8% of cases and a cost saving of US$495 per patient. It also accurately detected HCC in high-risk cases where CT or MRI were equivocal or normal. Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.

9.
Integr Med Res ; 13(2): 101041, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38948488

RESUMEN

Background: Investigating the effects of electroacupuncture (EA) treatment on cardiovascular function and aortic lipid profiles in spontaneously hypertensive rats (SHR) constitutes the foundational focus of this study. The overarching goal is to comprehensively elucidate the alterations brought about by EA treatment and to assess its potential as an alternative therapy for hypertension. Methods: Consecutive EA treatments were administered to SHR, and the effects on systolic blood pressure, cardiac function, and hypertension-related neuronal signals were assessed. Aortic lipid profiles in vehicle-treated SHR and EA-treated SHR groups were analyzed using mass spectrometry-based lipid profiling. Additionally, the expression of Cers2 and GNPAT, enzymes involved in the synthesis of specific aortic lipids, was examined. Results: The study demonstrated that consecutive EA treatments restored systolic blood pressure, improved cardiovascular function, and normalized hypertension-related neuronal signals in SHR. Analysis of the aortic lipid profiles revealed distinct differences between the vehicle-treated SHR group and the EA-treated SHR group. Specifically, EA treatment significantly altered the levels of aortic sphingomyelin and phospholipids, including very long-chain fatty acyl-ceramides and ether phosphatidylcholines. These changes in aortic lipid profiles correlated significantly with systolic blood pressure and cardiac function indicators. Furthermore, EA treatment significantly altered the expression of Cers2 and GNPAT. Conclusions: The findings suggest that EA may influence cardiovascular functions and aortic lipid profiles in SHR.

10.
Med Phys ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38978162

RESUMEN

BACKGROUND: Intensity modulation with dynamic multi-leaf collimator (MLC) and monitor unit (MU) changes across control points (CPs) characterizes volumetric modulated arc therapy (VMAT). The increased uncertainty in plan deliverability required patient-specific quality assurance (PSQA), which remained inefficient upon Quality Assurance (QA) failure. To prevent waste before QA, plan complexity metrics (PCMs) and machine learning models with the metrics were generated, which were lack of providing CP-specific information upon QA failures. PURPOSE: By generating 3D images from digital imaging and comminications in medicine in radiation therapy (DICOM RT) plan, we proposed a predictive model that can estimate the deliverability of VMAT plans and visualize CP-specific regions associated with plan deliverability. METHODS: The patient cohort consisted of 259 and 190 cases for left- and right-breast VMAT treatments, which were split into 235 and 166 cases for training and 24 cases from each treatment for testing the networks. Three-channel 3D images generated from DICOM RT plans were fed into a DenseNet-based deep learning network. To reflect VMAT plan complexity as an image, the first two channels described MLC and MU variations between two consecutive CPs, while the last channel assigned the beam field size. The network output was defined as binary classified PSQA results, indicating deliverability. The predictive performance was assessed by accuracy, sensitivity, specificity, F1-score, and area under the curve (AUC). The gradient-weighted class activation map (Grad-CAM) highlighted the regions of CPs in VMAT plans associated with deliverability, compared against PCMs by Spearman correlation. RESULTS: The DenseNet-based predictive model yielded AUCs of 92.2% and 93.8%, F1-scores of 97.0% and 93.8% and accuracies of 95.8% and 91.7% for the left- and right-breast VMAT cases. Additionally, the specificity of 87.5% for both cases indicated that the predictive model accurately detected QA failing cases. The activation maps significantly differentiated QA failing-labeled from passing-labeled classes for the non-deliverable cases. The PCM with the highest correlation to the Grad-CAM varied from patient cases, implying that plan deliverability would be considered patient-specific. CONCLUSION: This work demonstrated that the deep learning-based network based on visualization of dynamic VMAT plan information successfully predicted plan deliverability, which also provided control-point specific planning parameter information associated with plan deliverability in a patient-specific manner.

11.
Ecotoxicol Environ Saf ; 281: 116598, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38896897

RESUMEN

Bisphenol AF (BPAF) is found in high concentrations in aquatic environments due to the increased use of thermal paper and food packaging. However, there have been relatively few toxicological studies and potential risk assessments of BPAF. In this study, the risk quotient (RQ) and hazard quotient (HQ) of BPAF were derived to present the safety standards for environmental risk management and protection in lakes, rivers, bays, and Italian regions. We applied the species sensitivity distribution (SSD) method based on the previous ecotoxicological data and the results of supplementary toxicity tests on BPAF. From the SSD curves, the hazardous concentration for 5 % of the species (HC5) values for the acute and chronic toxicity data were 464.75 µg/L and 3.59 µg/L, respectively, and the acute- and chronic-based predicted no-effect concentration were derived as 154.92 µg/L and 1.20 µg/L, respectively. The acute-based RQ (RQA)values of BPAF in all regions were negligible (RQ < 0.1). The chronic-based RQ (RQC) in the Xitang River (XR) and the Central Italy (CI) showed a considerably high ecological risk (12.77 and 1.29) and the Hangzhou Bay (0.21), the South and North Italy (0.79 and 0.27), and the Tamagawa River (0.13) had a medium ecological risk (0.1 < RQ < 1.0). However, the HQ values based on the tolerable daily intake for BPAF over all age groups in these regions was < 0.1, indicating the low health risk. Nonetheless, the result of this study indicates that BPAF contamination is serious in XR and CI, and their use and emissions require continuous monitoring.


Asunto(s)
Compuestos de Bencidrilo , Monitoreo del Ambiente , Fenoles , Contaminantes Químicos del Agua , Medición de Riesgo , Fenoles/toxicidad , Fenoles/análisis , Compuestos de Bencidrilo/toxicidad , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , Italia , Humanos , Monitoreo del Ambiente/métodos , Animales , Ríos/química , Adulto , Niño , Exposición a Riesgos Ambientales , Fluorocarburos
12.
Exp Mol Med ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38945956

RESUMEN

Angiotensin II (AngII) induces the contraction and proliferation of vascular smooth muscle cells (VSMCs). AngII activates phospholipase C-ß (PLC-ß), thereby inducing Ca2+ mobilization as well as the production of reactive oxygen species (ROS). Since contraction is a unique property of contractile VSMCs, signaling cascades related to the proliferation of VSMCs may differ. However, the specific molecular mechanism that controls the contraction or proliferation of VSMCs remains unclear. AngII-induced ROS production, migration, and proliferation were suppressed by inhibiting PLC-ß3, inositol trisphosphate (IP3) receptor, and NOX or by silencing PLC-ß3 or NOX1 but not by NOX4. However, pharmacological inhibition or silencing of PLC-ß3 or NOX did not affect AngII-induced VSMC contraction. Furthermore, the AngII-dependent constriction of mesenteric arteries isolated from PLC-ß3∆SMC, NOX1-/-, NOX4-/- and normal control mice was similar. AngII-induced VSMC contraction and mesenteric artery constriction were blocked by inhibiting the L-type calcium channel Rho-associated kinase 2 (ROCK2) or myosin light chain kinase (MLCK). The activation of ROCK2 and MLCK was significantly induced in PLC-ß3∆SMC mice, whereas the depletion of Ca2+ in the extracellular medium suppressed the AngII-induced activation of ROCK2, MLCK, and vasoconstriction. AngII-induced hypertension was significantly induced in NOX1-/- and PLC-ß3∆SMC mice, whereas LCCA ligation-induced neointima formation was significantly suppressed in NOX1-/- and PLC-ß3∆SMC mice. These results suggest that PLC-ß3 is essential for vascular hyperplasia through NOX1-mediated ROS production but is nonessential for vascular constriction or blood pressure regulation.

13.
Clin Orthop Surg ; 16(3): 461-469, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38827764

RESUMEN

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder that frequently causes forefoot deformities. Arthrodesis of the first metatarsophalangeal joint is a common surgery for severe hallux valgus. However, joint-preserving surgery can maintain the mobility of the joint. This study aimed to investigate the clinical and radiographic outcomes of distal chevron metatarsal osteotomy (DCMO) for correcting hallux valgus deformity associated with RA. Methods: Between August 2000 and December 2018, 18 consecutive patients with rheumatoid forefoot deformities (24 feet) underwent DCMO for hallux valgus with/without lesser toe surgery. Radiological evaluations were conducted, assessing the hallux valgus angle, the intermetatarsal angle between the first and second metatarsals, and the Sharp/van der Heijde score for erosion and joint space narrowing. Clinical outcomes were quantified using a visual analog scale for pain and the American Orthopaedic Foot and Ankle Society forefoot scores to measure function and alignment. Results: The mean hallux valgus angle decreased from 38.0° (range, 25°-65°) preoperatively to 3.5° (range, 0°-17°) at the final follow-up (p < 0.05). The mean intermetatarsal angle decreased from 14.9° (range, 5°-22°) preoperatively to 4.3° (range, 2°-11°) at the final follow-up. (p < 0.05). Regarding the Sharp/van der Heijde score, the mean erosion score (0-10) showed no significant change, decreasing from 3.83 (range, 0-6) preoperatively to 3.54 (range, 0-4) at the final follow-up (p = 0.12). Recurrent hallux valgus was observed in 1 patient and postoperative hallux varus deformity was observed in 2 feet. Spontaneous fusion of the metatarsophalangeal joint developed in 1 case. Conclusions: DCMO resulted in satisfactory clinical and radiographic outcomes for correcting RA-associated hallux valgus deformity.


Asunto(s)
Artritis Reumatoide , Hallux Valgus , Osteotomía , Humanos , Hallux Valgus/cirugía , Hallux Valgus/diagnóstico por imagen , Artritis Reumatoide/cirugía , Artritis Reumatoide/complicaciones , Femenino , Persona de Mediana Edad , Osteotomía/métodos , Masculino , Anciano , Adulto , Estudios Retrospectivos
14.
Nat Commun ; 15(1): 4909, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38851766

RESUMEN

Tobacco smoking (TS) is implicated in lung cancer (LC) progression through the development of metabolic syndrome. However, direct evidence linking metabolic syndrome to TS-mediated LC progression remains to be established. Our findings demonstrate that 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene (NNK and BaP; NB), components of tobacco smoke, induce metabolic syndrome characteristics, particularly hyperglycemia, promoting lung cancer progression in male C57BL/6 J mice. NB enhances glucose uptake in tumor-associated macrophages by increasing the expression and surface localization of glucose transporter (GLUT) 1 and 3, thereby leading to transcriptional upregulation of insulin-like growth factor 2 (IGF2), which subsequently activates insulin receptor (IR) in LC cells in a paracrine manner, promoting its nuclear import. Nuclear IR binds to nucleophosmin (NPM1), resulting in IR/NPM1-mediated activation of the CD274 promoter and expression of programmed death ligand-1 (PD-L1). Restricting glycolysis, depleting macrophages, or blocking PD-L1 inhibits NB-mediated LC progression. Analysis of patient tissues and public databases reveals elevated levels of IGF2 and GLUT1 in tumor-associated macrophages, as well as tumoral PD-L1 and phosphorylated insulin-like growth factor 1 receptor/insulin receptor (pIGF-1R/IR) expression, suggesting potential poor prognostic biomarkers for LC patients. Our data indicate that paracrine IGF2/IR/NPM1/PD-L1 signaling, facilitated by NB-induced dysregulation of glucose levels and metabolic reprogramming of macrophages, contributes to TS-mediated LC progression.


Asunto(s)
Antígeno B7-H1 , Benzo(a)pireno , Progresión de la Enfermedad , Hiperglucemia , Factor II del Crecimiento Similar a la Insulina , Neoplasias Pulmonares , Ratones Endogámicos C57BL , Proteínas Nucleares , Nucleofosmina , Receptor de Insulina , Animales , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Masculino , Humanos , Receptor de Insulina/metabolismo , Receptor de Insulina/genética , Ratones , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Hiperglucemia/metabolismo , Benzo(a)pireno/toxicidad , Factor II del Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Nitrosaminas/toxicidad , Macrófagos Asociados a Tumores/metabolismo , Línea Celular Tumoral , Comunicación Paracrina , Regulación Neoplásica de la Expresión Génica , Fumar/efectos adversos , Macrófagos/metabolismo
15.
Cancer Res Treat ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38938009

RESUMEN

Purpose: To develop an MRI-based radiomics model to predict high-risk pathologic features for lung adenocarcinoma: micropapillary and solid pattern (MPsol), spread through air space (STAS), and poorly differentiated patterns. Materials and Methods: As a prospective study, we screened clinical N0 lung cancer patients who were surgical candidates and had undergone both 18F-fluorodeoxyglucose (FDG) positron emission tomography-CT (PET/CT) and chest CT from August 2018 to January 2020. We recruited patients meeting our proposed imaging criteria indicating high-risk, that is, poorer prognosis of lung adenocarcinoma, using CT and FDG PET/CT. If possible, these patients underwent an MRI examination from which we extracted 77 radiomics features from T1-contrast-enhanced and T2-weighted images. Additionally, patient demographics, SUVmax (maximum standardized uptake value) on FDG PET/CT, and the mean ADC value on DWI, were considered together to build prediction models for high-risk pathologic features. Results: Among 616 patients, 72 patients met the imaging criteria for high-risk lung cancer and underwent lung MRI. The MR-eligible group showed a higher prevalence of nodal upstaging (29.2% vs. 4.2%, p<0.001), vascular invasion (6.5% vs. 2.1%, p=0.011), high-grade pathologic features (p<0.001), worse 4-year disease free survival (p<0.001) compared with non-MR-eligible group. The prediction power for MR-based radiomics model predicting high-risk pathologic features was good, with mean area under the receiver operating curve (AUC) value measuring 0.751-0.886 in test sets. Adding clinical variables increased the predictive performance for MPsol and the poorly differentiated pattern using the 2021 grading system (AUC 0.860 and 0.907, respectively). Conclusion: Our imaging criteria can effectively screen high-risk lung cancer patients and predict high-risk pathologic features by our MR-based prediction model using radiomics.

16.
Plants (Basel) ; 13(12)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38931087

RESUMEN

Cryopreservation is a promising method for the long-term preservation of plant germplasm, especially for vegetatively propagated species like freesias. In this study, we investigate streamlining the cryopreservation process for 'Sunny Gold' Freesia, starting from effective in vitro initiation and proliferation using various plant growth regulator combinations. We also assess the impact of subculture on regrowth rates after cryopreservation. The shoot tips were successfully initiated in vitro after sterilization. The shoots were multiplied an average of three times in media containing N6-benzyladenine and kinetin. The regrowth rates of non-cryopreserved shoot tips excised from different subculture cycles did not differ significantly, with rates of 44% observed for plants from more than five subcultures and 47% for those from three subcultures. However, only the shoot tips excised from cultures subjected to three subculture cycles were able to recover after cryopreservation, with a regrowth rate of 31%. Our findings lay the groundwork for the development of an efficient cryopreservation protocol for freesias in the future.

17.
Anticancer Res ; 44(7): 3163-3173, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38925826

RESUMEN

BACKGROUND/AIM: Although the importance of low-dose computed tomography (LDCT) screening is increasingly emphasized and implemented, many lung cancers continue to be incidentally detected during routine medical practices, and data on incidentally detected lung cancer (IDLC) remain scarce. This study aimed to investigate the clinical characteristics and prognosis of IDLCs by comparing them with screening-detected lung cancers (SDLCs). PATIENTS AND METHODS: In this retrospective study, subjects with cT1 (≤3 cm) pulmonary nodules detected on baseline computed tomography (CT), later pathologically confirmed as primary lung cancer in 2015, were included. Patients were categorized into IDLC and SDLC groups based on the setting of the first pulmonary nodule detection. RESULTS: Out of 457 subjects, 129 (28.2%) were IDLCs and 328 (71.8%) were SDLCs. The IDLC group, consisted of older individuals with a higher prevalence of smokers and underlying pulmonary disease, compared to the SDLC group. Adenocarcinomas were more frequently detected in SDLCs (87.5%) than in IDLCs (76.7%, p<0.001). The time to treatment initiation (TTI) and 5-year overall survival (OS) rates were similar. Multivariate analyses revealed underlying interstitial lung disease, DLCO, solidity of nodules and TNM stage as independent risk factors associated with mortality. Less than 30% of study participants would have been eligible for the current lung cancer screening program. CONCLUSION: The IDLC group was associated with older age, higher rate of smokers, underlying pulmonary disease, and non-adenocarcinoma histology. However, prognosis was similar to that of the SDLC group, attributable to the similarity in TNM stage, strict adherence to guidelines, and short TTI. Furthermore, less than 30% of the participants would have been suitable for the existing lung cancer screening program, indicating a potential need to reconsider the scope for screening candidates.


Asunto(s)
Detección Precoz del Cáncer , Hallazgos Incidentales , Neoplasias Pulmonares , Tomografía Computarizada por Rayos X , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/mortalidad , Masculino , Femenino , Anciano , Pronóstico , Persona de Mediana Edad , Detección Precoz del Cáncer/métodos , Estudios Retrospectivos , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/patología , Nódulos Pulmonares Múltiples/mortalidad , Nódulo Pulmonar Solitario/diagnóstico por imagen , Nódulo Pulmonar Solitario/patología , Nódulo Pulmonar Solitario/diagnóstico
18.
Endocrinol Metab (Seoul) ; 39(3): 521-530, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38858821

RESUMEN

BACKGRUOUND: Aging leads to sarcopenia, which is characterized by reduced muscle mass and strength. Many factors, including altered muscle protein turnover, diminished neuromuscular function, hormonal changes, systemic inflammation, and the structure and composition of muscle fibers, play a crucial role in age-related muscle decline. This study explored differences in muscle fiber types contributing to overall muscle function decline in aging, focusing on individuals with hip fractures from falls. METHODS: A pilot study at Chungnam National University Hospital collected muscle biopsies from hip fracture patients aged 20 to 80 undergoing surgical treatment. Muscle biopsies from the vastus lateralis and gluteus maximus were obtained during hip arthroplasty or internal fixation. Handgrip strength, calf and thigh circumference, and bone mineral density were evaluated in individuals with hip fractures from falls. We analyzed the relationships between each clinical characteristic and muscle fiber type. RESULTS: In total, 26 participants (mean age 67.9 years, 69.2% male) were included in this study. The prevalence of sarcopenia was 53.8%, and that of femoral and lumbar osteoporosis was 19.2% and 11.5%, respectively. Vastus lateralis analysis revealed an age-related decrease in type IIx fibers, a higher proportion of type IIa fibers in women, and an association between handgrip strength and type IIx fibers in men. The gluteus maximus showed no significant correlations with clinical parameters. CONCLUSION: This study identified complex associations between age, sex, handgrip strength, and muscle fiber composition in hip fracture patients, offering insights crucial for targeted interventions combating age-related muscle decline and improving musculoskeletal health.


Asunto(s)
Fracturas de Cadera , Músculo Cuádriceps , Sarcopenia , Humanos , Masculino , Femenino , Anciano , Fracturas de Cadera/patología , Sarcopenia/patología , Músculo Cuádriceps/patología , Persona de Mediana Edad , Proyectos Piloto , Anciano de 80 o más Años , Fuerza de la Mano , Adulto , Densidad Ósea , Fibras Musculares Esqueléticas/patología , Fibras Musculares Esqueléticas/metabolismo , Adulto Joven , Envejecimiento/fisiología , Envejecimiento/patología , Fibras Musculares de Contracción Rápida/patología , Fibras Musculares de Contracción Rápida/metabolismo
19.
Phys Med ; 123: 103414, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38906047

RESUMEN

PURPOSE: This study reviewed and meta-analyzed evidence on radiomics-based hybrid models for predicting radiation pneumonitis (RP). These models are crucial for improving thoracic radiotherapy plans and mitigating RP, a common complication of thoracic radiotherapy. We examined and compared the RP prediction models developed in these studies with the radiomics features employed in RP models. METHODS: We systematically searched Google Scholar, Embase, PubMed, and MEDLINE for studies published up to April 19, 2024. Sixteen studies met the inclusion criteria. We compared the RP prediction models developed in these studies and the radiomics features employed. RESULTS: Radiomics, as a single-factor evaluation, achieved an area under the receiver operating characteristic curve (AUROC) of 0.73, accuracy of 0.69, sensitivity of 0.64, and specificity of 0.74. Dosiomics achieved an AUROC of 0.70. Clinical and dosimetric factors showed lower performance, with AUROCs of 0.59 and 0.58. Combining clinical and radiomic factors yielded an AUROC of 0.78, while combining dosiomic and radiomics factors produced an AUROC of 0.81. Triple combinations, including clinical, dosimetric, and radiomics factors, achieved an AUROC of 0.81. The study identifies key radiomics features, such as the Gray Level Co-occurrence Matrix (GLCM) and Gray Level Size Zone Matrix (GLSZM), which enhance the predictive accuracy of RP models. CONCLUSIONS: Radiomics-based hybrid models are highly effective in predicting RP. These models, combining traditional predictive factors with radiomic features, particularly GLCM and GLSZM, offer a clinically feasible approach for identifying patients at higher RP risk. This approach enhances clinical outcomes and improves patient quality of life. PROTOCOL REGISTRATION: The protocol of this study was registered on PROSPERO (CRD42023426565).


Asunto(s)
Neumonitis por Radiación , Humanos , Neumonitis por Radiación/diagnóstico por imagen , Neumonitis por Radiación/etiología , Radiómica
20.
Anesth Analg ; 139(1): 114-123, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38885399

RESUMEN

BACKGROUND: Many studies have suggested that volatile anesthetic use may improve postoperative outcomes after cardiac surgery compared to total intravenous anesthesia (TIVA) owing to its potential cardioprotective effect. However, the results were inconclusive, and few studies have included patients undergoing heart valve surgery. METHODS: This nationwide population-based study included all adult patients who underwent heart valve surgery between 2010 and 2019 in Korea based on data from a health insurance claim database. Patients were divided based on the use of volatile anesthetics: the volatile anesthetics or TIVA groups. After stabilized inverse probability of treatment weighting (IPTW), the association between the use of volatile anesthetics and the risk of cumulative 1-year all-cause mortality (the primary outcome) and cumulative long-term (beyond 1 year) mortality were assessed using Cox regression analysis. RESULTS: Of the 30,755 patients included in this study, the overall incidence of 1-year mortality was 8.5%. After stabilized IPTW, the risk of cumulative 1-year mortality did not differ in the volatile anesthetics group compared to the TIVA group (hazard ratio, 0.98; 95% confidence interval, 0.90-1.07; P = .602), nor did the risk of cumulative long-term mortality (hazard ratio, 0.98; 95% confidence interval, 0.93-1.04; P = .579) at a median (interquartile range) follow-up duration of 4.8 (2.6-7.6) years. CONCLUSIONS: Compared with TIVA, volatile anesthetic use was not associated with reduced postoperative mortality risk in patients undergoing heart valve surgery. Our findings indicate that the use of volatile anesthetics does not have a significant impact on mortality after heart valve surgery. Therefore, the choice of anesthesia type can be based on the anesthesiologists' or institutional preference and experience.


Asunto(s)
Anestesia Intravenosa , Anestésicos por Inhalación , Válvulas Cardíacas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anestesia Intravenosa/efectos adversos , Anestesia Intravenosa/mortalidad , Anciano , Anestésicos por Inhalación/administración & dosificación , Anestésicos por Inhalación/efectos adversos , República de Corea/epidemiología , Válvulas Cardíacas/cirugía , Adulto , Procedimientos Quirúrgicos Cardíacos/mortalidad , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Resultado del Tratamiento , Estudios Retrospectivos , Bases de Datos Factuales , Factores de Riesgo , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Anestesia por Inhalación/efectos adversos , Anestesia por Inhalación/mortalidad , Factores de Tiempo
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