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1.
Sci Rep ; 14(1): 14619, 2024 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918416

RESUMEN

High-risk human papillomavirus (HR-HPV) is the primary carcinogen in uterine cervical carcinoma. While genotype-specific carcinogenic risks have been extensively studied in Western populations, data from Korean are sparse. This study evaluates the malignant potential of the three most prevalent HR-HPVs in Korea: HPV16, HPV52, and HPV58. We analyzed 230 patients who underwent cervical conization and had been tested for HPV within a year prior to the procedure, excluding those with multiple infections. This analysis was confined to patients with single HPV infections and assessed outcomes of CIN3+, which includes carcinoma in situ (CIN3) and invasive carcinoma. The incidence of invasive cervical cancer was 6.7% for HPV16, 1.7% for HPV52, and 2.0% for HPV58; however, these differences were not statistically significant (p = 0.187). The rate of CIN3+ for HPV16, HPV52, and HPV58 were 70.6%, 51.7%, and 58.8%, respectively. Despite the small sample size, which may limit the robustness of statistical analysis, the data suggest a higher observed risk with HPV16. These findings highlight the need for vigilant clinical management tailored to specific HPV genotypes and support the implementation of a nine-valent vaccine in Korea. Physicians should be aware of these genotype-specific risks when treating patients.


Asunto(s)
Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , República de Corea/epidemiología , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/patología , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/epidemiología , Adulto , Persona de Mediana Edad , Papillomavirus Humano 16/genética , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/epidemiología , Cuello del Útero/virología , Cuello del Útero/patología , Genotipo , Estudios de Cohortes , Anciano , Papillomaviridae/genética , Incidencia
2.
Nanotechnology ; 35(37)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38876085

RESUMEN

This study introduces a novel heteroleptic indium complex, which incorporates an amidinate ligand, serving as a high-temperature atomic layer deposition (ALD) precursor. The most stable structure was determined using density functional theory and synthesized, demonstrating thermal stability up to 375 °C. We fabricated indium oxide thin-film transistors (In2O3TFTs) prepared with DBADMI precursor using ALD in wide range of window processing temperature of 200 °C, 300 °C, and 350 °C with an ozone (O3) as the source. The growth per cycle of ALD ranged from 0.06 to 0.1 nm cycle-1at different deposition temperatures. X-ray diffraction and transmission electron microscopy were employed to analyze the crystalline structure as it relates to the deposition temperature. At a relatively low deposition temperature of 200 °C, an amorphous morphology was observed, while at 300 °C and 350 °C, crystalline structures were evident. Additionally, x-ray photoelectron spectroscopy analysis was conducted to identify the In-O and OH-related products in the film. The OH-related product was found to be as low as 1% with an increase the deposition temperature. Furthermore, we evaluated In2O3TFTs and observed an increase in field-effect mobility, with minimal change in the threshold voltage (Vth), at 200 °C, 300 °C, and 350 °C. Consequently, the DBADMI precursor, given its stability at highdeposition temperatures, is ideal for producing high-quality films and stable crystalline phases, with wide processing temperature range makeing it suitable for various applications.

3.
J Clin Med ; 13(10)2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38792331

RESUMEN

INTRODUCTION: Solid pseudopapillary neoplasms (SPNs) are rare and mainly originate from the pancreas. SPNs originating from the ovary (SPN-O) are extremely rare, and only 13 cases have been reported in the English literature since 2010. CASE: We report a 31-year-old woman with SPN-O accompanied by multiple metastases in the abdominal cavity. The patient underwent staging surgery and cytoreduction. Furthermore, the multidisciplinary board decided on adjuvant chemotherapy with an FP regimen (fluorouracil plus cisplatin) because a microscopic metastasis was discovered in the peritoneum near the appendix. Next-generation sequencing showed some pathologic mutations of oncogenes/cancer-associated genes, including CTNNB1 and TP53. This is the fourteenth case of SPN-O and the first one to demonstrate the TP53 pathogenic mutant variant in SPN-O. The patient showed 8 months of disease-free survival until February 2024. CONCLUSION: The combination of R0 cytoreduction with FOLFIRI chemotherapy appears to be an effective and feasible treatment option.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38652271

RESUMEN

OBJECTIVE: BRCA1/2 are integral to the DNA repair mechanism and their germline pathogenic variants (gBRCA) result in a high risk for developing breast and ovarian cancer. Patients with gBRCA mutations showed increased sensitivity to DNA cross-linking agent but might have increased treatment-related toxicities. Thus, we hypothesized that gBRCA mutation ovarian cancer patients who underwent platinum-based chemotherapy might be at higher risk of developing chemotherapy-induced hematologic toxicity. METHODS: This study enrolled 160 patients with ovarian cancer who received frontline platinum-based chemotherapy between 2011 and 2019 in Kyungpook National University Chilgok Hospital. Incidence rate and severity of chemotherapy-induced hematologic toxicity (neutropenia, anemia, thrombocytopenia) was compared for BRCA mutation and wild patients. RESULTS: 160 women, including 62 BRCA1/2 (38 BRCA1, and 25 BRCA2) mutation group, and 98 noncarriers, were analyzed. A higher frequency of G2 anemia was noted in the BRCA -mutant group (22% vs. 1%, p = 0.07). Furthermore, G3 anemia was significantly common among BRCA group (12.9% vs. 3%, p = 0.02). In the subgroup analysis according to BRCA1/2 status, BRCA1 mutated patients showed a significantly higher frequency of G1 anemia than BRCA2 (89% vs. 60%, p = 0.01). In terms of neutropenia and thrombocytopenia, BRCA mutated patients and noncarriers had similar hematologic toxicity. CONCLUSION: Germline BRCA mutations were associated with a higher frequency of G2/3 anemia in ovarian cancer patients who underwent first-line platinum-based chemotherapy. Moreover, the BRCA1 mutation appeared to be more strongly associated with the incidence of chemotherapy-induced anemia. Our findings warrant further investigation in larger, prospective studies to confirm these current findings and determine whether preventive interventions may be necessary.

5.
Nat Immunol ; 25(5): 790-801, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38664585

RESUMEN

Innate immune cells generate a multifaceted antitumor immune response, including the conservation of essential nutrients such as iron. These cells can be modulated by commensal bacteria; however, identifying and understanding how this occurs is a challenge. Here we show that the food commensal Lactiplantibacillus plantarum IMB19 augments antitumor immunity in syngeneic and xenograft mouse tumor models. Its capsular heteropolysaccharide is the major effector molecule, functioning as a ligand for TLR2. In a two-pronged manner, it skews tumor-associated macrophages to a classically active phenotype, leading to generation of a sustained CD8+ T cell response, and triggers macrophage 'nutritional immunity' to deploy the high-affinity iron transporter lipocalin-2 for capturing and sequestering iron in the tumor microenvironment. This process induces a cycle of tumor cell death, epitope expansion and subsequent tumor clearance. Together these data indicate that food commensals might be identified and developed into 'oncobiotics' for a multi-layered approach to cancer therapy.


Asunto(s)
Hierro , Microambiente Tumoral , Animales , Hierro/metabolismo , Ratones , Microambiente Tumoral/inmunología , Humanos , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 2/inmunología , Ratones Endogámicos C57BL , Lipocalina 2/metabolismo , Lipocalina 2/inmunología , Femenino , Simbiosis/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Activación de Macrófagos/inmunología , Ratones Noqueados
6.
Proc Natl Acad Sci U S A ; 121(8): e2316871121, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38346184

RESUMEN

Postmenopausal osteoporosis arises from imbalanced osteoclast and osteoblast activity, and mounting evidence suggests a role for the osteoimmune system in bone homeostasis. Bisphosphonate (BP) is an antiresorptive agent, but its treatment failure rate can be as high as 40%. Here, we performed single-cell RNA sequencing on peripheral immune cells from carefully selected postmenopausal women: non-osteoporotic, osteoporosis improved after BP treatment, and BP-failed cases. We found an increase in myeloid cells in patients with osteoporosis (specifically, T cell receptor+ macrophages). Furthermore, lymphoid lineage cells varied significantly, notably elevated natural killer cells (NKs) in the BP-failed group. Moreover, we provide fruitful lists of biomarkers within the immune cells that exhibit condition-dependent differences. The existence of osteoporotic- and BP-failure-specific cellular information flows was revealed by cell-cell interaction analysis. These findings deepen our insight of the osteoporosis pathology enhancing comprehension of the role of immune heterogeneity in postmenopausal osteoporosis and BP treatment failure.


Asunto(s)
Conservadores de la Densidad Ósea , Osteoporosis Posmenopáusica , Osteoporosis , Humanos , Femenino , Difosfonatos/farmacología , Difosfonatos/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/genética , Densidad Ósea , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Osteoporosis/tratamiento farmacológico , Osteoporosis/genética , Perfilación de la Expresión Génica
7.
Breast Cancer Res ; 26(1): 21, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38303004

RESUMEN

BACKGROUND: The wide heterogeneity in the appearance of breast lesions and normal breast structures can confuse computerized detection algorithms. Our purpose was therefore to develop a Lesion Highlighter (LH) that can improve the performance of computer-aided detection algorithms for detecting breast cancer on screening mammograms. METHODS: We hypothesized that a Cycle-GAN based Lesion Remover (LR) could act as an LH, which can improve the performance of lesion detection algorithms. We used 10,310 screening mammograms from 4,832 women that included 4,942 recalled lesions (BI-RADS 0) and 5,368 normal results (BI-RADS 1). We divided the dataset into Train:Validate:Test folds with the ratios of 0.64:0.16:0.2. We segmented image patches (400 × 400 pixels) from either lesions marked by MQSA radiologists or normal tissue in mammograms. We trained a Cycle-GAN to develop two GANs, where each GAN transferred the style of one image to another. We refer to the GAN transferring the style of a lesion to normal breast tissue as the LR. We then highlighted the lesion by color-fusing the mammogram after applying the LR to its original. Using ResNet18, DenseNet201, EfficientNetV2, and Vision Transformer as backbone architectures, we trained three deep networks for each architecture, one trained on lesion highlighted mammograms (Highlighted), another trained on the original mammograms (Baseline), and Highlighted and Baseline combined (Combined). We conducted ROC analysis for the three versions of each deep network on the test set. RESULTS: The Combined version of all networks achieved AUCs ranging from 0.963 to 0.974 for identifying the image with a recalled lesion from a normal breast tissue image, which was statistically improved (p-value < 0.001) over their Baseline versions with AUCs that ranged from 0.914 to 0.967. CONCLUSIONS: Our results showed that a Cycle-GAN based LR is effective for enhancing lesion conspicuity and this can improve the performance of a detection algorithm.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Mamografía/métodos , Mama/diagnóstico por imagen , Mama/patología , Algoritmos , Curva ROC
8.
Sci Adv ; 10(5): eadj0785, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38295179

RESUMEN

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, only some patients respond to ICIs, and current biomarkers for ICI efficacy have limited performance. Here, we devised an interpretable machine learning (ML) model trained using patient-specific cell-cell communication networks (CCNs) decoded from the patient's bulk tumor transcriptome. The model could (i) predict ICI efficacy for patients across four cancer types (median AUROC: 0.79) and (ii) identify key communication pathways with crucial players responsible for patient response or resistance to ICIs by analyzing more than 700 ICI-treated patient samples from 11 cohorts. The model prioritized chemotaxis communication of immune-related cells and growth factor communication of structural cells as the key biological processes underlying response and resistance to ICIs, respectively. We confirmed the key communication pathways and players at the single-cell level in patients with melanoma. Our network-based ML approach can be used to expand ICIs' clinical benefits in cancer patients.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Melanoma , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Comunicación Celular , Quimiotaxis , Aprendizaje Automático
9.
Ther Adv Neurol Disord ; 17: 17562864231218181, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38250318

RESUMEN

Background: The brain-gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement. Objective: This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer's dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT. Methods: Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients' fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients' genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction. Results: Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3 months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes via 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT. Conclusion: These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.

10.
J Med Imaging (Bellingham) ; 10(5): 054503, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37840849

RESUMEN

Purpose: Generative adversarial networks (GANs) can synthesize various feasible-looking images. We showed that a GAN, specifically a conditional GAN (CGAN), can simulate breast mammograms with normal, healthy appearances and can help detect mammographically-occult (MO) cancer. However, similar to other GANs, CGANs can suffer from various artifacts, e.g., checkerboard artifacts, that may impact the quality of the final synthesized image, as well as the performance of detecting MO cancer. We explored the types of GAN artifacts that exist in mammogram simulations and their effect on MO cancer detection. Approach: We first trained a CGAN using digital mammograms (FFDMs) of 1366 women with normal/healthy breasts. Then, we tested the trained CGAN on an independent MO cancer dataset with 333 women with dense breasts (97 MO cancers). We trained a convolutional neural network (CNN) on the MO cancer dataset, in which real and simulated mammograms were fused, to identify women with MO cancer. Then, a radiologist who was independent of the development of the CGAN algorithms evaluated the entire MO cancer dataset to identify and annotate artifacts in the simulated mammograms. Results: We found four artifact types, including checkerboard, breast boundary, nipple-areola complex, and black spots around calcification artifacts, with an overall incidence rate over 69% (the individual incident rate ranged from 9% to 53%) from both normal and MO cancer samples. We then evaluated their potential impact on MO cancer detection. Even though various artifacts existed in the simulated mammogram, we found that it still provided complementary information for MO cancer detection when it was combined with the real mammograms. Conclusions: We found that artifacts were pervasive in the CGAN-simulated mammograms. However, they did not negatively affect our MO cancer detection algorithm; the simulated mammograms still provided complementary information for MO cancer detection when combined with real mammograms.

11.
J Clin Med ; 12(19)2023 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-37834799

RESUMEN

The high-risk human papillomavirus (HR-HPV) has been known as the most important carcinogen in uterine cervical carcinoma. However, there is limited evidence of the malignant potential of these concurrent multiple infections. This study included women who had undergone cervical conization. They underwent an HPV test by cervical swab within 12 months before the surgery. They were divided into two groups: one with a single infection with HR-HPV16 and the other with concurrent multiple infections with HR-HPVs, including genotype 16. Pathologic examination classified cases as CIS+ to assess and compare the malignant potential in both groups, including carcinoma in situ (CIS) and invasive carcinoma. Of the 220 patients infected with HR-HPV16, the single infection group consisted of 120 patients (54.5%), whereas the concurrent multiple infections consisted of 100 (45.5%) patients. The rates of HSIL were significantly higher in the concurrent multiple infection group. However, the odds ratio for CIS+ did not show a significant difference between both groups (1.417, 95% CI = 0.831-2.414, p = 0.200). The malignant potential was not significantly different between concurrent multiple infections with HR-HPVs, including 16, and a single infection with 16 in Korean women.

12.
J Yeungnam Med Sci ; 40(Suppl): S65-S72, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37735856

RESUMEN

BACKGROUND: Over the last two decades, serum levels of anti-Müllerian hormone (AMH) have been shown to be reliable markers of ovarian reserve. This study aimed to compare baseline serum AMH levels and well-controlled clinical factors between patients with unilateral and bilateral ovarian endometriomas during the menstrual phase. METHODS: We conducted a retrospective study. We enrolled 136 patients aged 18 to 36 years who were diagnosed with unilateral or bilateral ovarian endometriomas. Serum AMH levels of all patients and their latest two to three menstrual cycles were measured before surgery for ovarian endometriomas. The latest menstrual cycle length ranged from 26 to 30 days. Patients with irregular menstruation, a recent medication history of hormonal drugs other than oral contraceptive pills, a previous history of ovarian surgery, or any medical history influencing ovarian function were excluded. RESULTS: Of the 136 patients, 76 (55.9%) had unilateral ovarian endometriomas and 60 (44.1%) had bilateral ovarian endometriomas. Serum AMH levels were not significantly different between the two groups in the follicular phase, luteal phase, or at any random time point. CONCLUSION: Serum AMH levels were not significantly different between unilateral and bilateral ovarian endometriomas in the follicular and luteal phases, or at any random time during the menstrual cycle when various confounding factors were excluded.

13.
Clin Neurol Neurosurg ; 233: 107915, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37556970

RESUMEN

OBJECTIVE: There is growing interest in the use of new biomarkers such as glycated albumin (GA). In contrast to glycated hemoglobin (HbA1c), GA showed an inverse correlation with prestroke obesity status, but data are limited for ischemic stroke (IS). MATERIALS AND METHODS: We explored the association between GA and body mass index (BMI) and investigated inflammatory cytokines to support the academic background. In total, 155 patients with hyperacute IS (HIS) between 2011 and 2019 were included. To identify the association between GA and BMI, patients were divided into four groups according to BMI quartiles. Levels of inflammatory cytokines, including IL-1ß, IL-10, IL-6, TNF-α, and TNF-R1, were determined by ELISA using a ProcartaPlex multiplex immunoassay. RESULTS: The mean age of the 155 patients was 68 ± 12 years, and 67.1% were men. The lowest BMI group had higher GA levels (GA 2 T and 3 T = 80%) (p-value=0.017), and these U-shaped associations were maintained only for small vessel occlusion etiology (p-value= 0.004). Plasma IL-10 levels were positively correlated with BMI and showed a U-shaped pattern (p-value= 0.001). CONCLUSION: GA levels and BMI had U-shaped associations with HIS. IL-10, which acts as a protective cytokine for cardiovascular disease, may play a novel role in this association. Although GA is an emerging favorable clinical marker of cardiovascular outcomes, obesity status should be considered when interpreting these associations.

14.
Patterns (N Y) ; 4(6): 100736, 2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37409049

RESUMEN

Predicting cancer recurrence is essential to improving the clinical outcomes of patients with colorectal cancer (CRC). Although tumor stage information has been used as a guideline to predict CRC recurrence, patients with the same stage show different clinical outcomes. Therefore, there is a need to develop a method to identify additional features for CRC recurrence prediction. Here, we developed a network-integrated multiomics (NIMO) approach to select appropriate transcriptome signatures for better CRC recurrence prediction by comparing the methylation signatures of immune cells. We validated the performance of the CRC recurrence prediction based on two independent retrospective cohorts of 114 and 110 patients. Moreover, to confirm that the prediction was improved, we used both NIMO-based immune cell proportions and TNM (tumor, node, metastasis) stage data. This work demonstrates the importance of (1) using both immune cell composition and TNM stage data and (2) identifying robust immune cell marker genes to improve CRC recurrence prediction.

15.
J Yeungnam Med Sci ; 40(Suppl): S87-S92, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37096360

RESUMEN

Diffuse large B-cell lymphoma (DLBCL) is a subtype of non-Hodgkin lymphoma (NHL) and is estimated to account for approximately 30% of all NHL cases. NHL can also occur in the female genital tract and accounts for approximately 1.5% of all NHL cases. Many doctors have difficulty diagnosing or treating vulvar DLBCL because of its very low prevalence. A 55-year-old woman presented with a solid mass on the right side of the vulva. No significantly enlarged lymph nodes were observed in the inguinal region. She underwent excisional biopsy at our institution. DLBCL was diagnosed based on histological examination. According to the Hans algorithm, the lesion was diagnosed as a non-germinal center B-cell-like subtype. The patient was referred to a hematologic oncologist. The disease stage was classified as IE according to the Ann Arbor staging classification. The patient received four cycles of chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and localized radiation therapy with 36 Gy in 20 fractions. She showed complete remission and maintained this status on the latest computed tomography scan. Gynecologists should rule out lymphoma in patients presenting with a vulvar mass.

16.
Front Plant Sci ; 14: 1138089, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36909433

RESUMEN

Plants have recently received much attention as a means of producing recombinant proteins because they are easy to grow at a low cost and at a large scale. Although many plant protein expression systems have been developed, there remains a need for improved systems that deliver high yields of recombinant proteins. Transcription of the recombinant gene is a key step in increasing the yield of recombinant proteins. However, revealed strong promoters, terminators, and transcription factors that have been identified do not necessarily lead to high level production of recombinant proteins. Thus, in this study, a robust expression system was designed to produce high levels of recombinant protein consisting of a novel hybrid promoter, FM'M-UD, coupled with an artificial terminator, 3PRt. FM'M-UD contained fragments from three viral promoters (the promoters of Mirabilis mosaic caulimovirus (MMV) full-length transcript, the MMV subgenomic transcript, and figwort mosaic virus subgenomic transcript) and two types of cis-acting elements (four GAL4 binding sites and two zinc finger binding sites). The artificial terminator, 3PRt, consisted of the PINII and 35S terminators plus RB7, a matrix attachment region. The FM'M-UD promoter increased protein levels of reporters GFP, RBD : SD1 (part of S protein from SARS-CoV-2), and human interleukin-6 (hIL6) by 4-6-fold, 2-fold, and 6-fold, respectively, relative to those of the same reporters driven by the CaMV 35S promoter. Furthermore, when the FM'M-UD/3PRt expression cassette was expressed together with GAL4/TAC3d2, an artificial transcription factor that bound the GAL4 binding sites in FM'M-UD, levels of hIL6 increased by 10.7-fold, relative to those obtained from the CaMV 35S promoter plus the RD29B terminator. Thus, this novel expression system led to the production of a large amount of recombinant protein in plants.

17.
J Neurol Sci ; 447: 120610, 2023 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-36898221

RESUMEN

BACKGROUND AND PURPOSE: Although supraventricular ectopic beats (SVE), including premature atrial contractions (PACs) and non-sustained atrial tachycardia (NSAT), are frequent in the general population, some study results indicate that they are pathologic. SVE may predict undiagnosed atrial fibrillation or be associated with the embolic pattern of ischemic stroke. The aim of this study was to identify the indicators most associated with embolic stroke among the parameters that suggest the burden of SVE. METHODS: A total of 1920 consecutive acute ischemic stroke (AIS) patients were enrolled from two university hospitals. We defined embolic stroke of unknown source (ESUS) and small vessel occlusion (SVO) etiologies using stricter criteria than the existing conventional criteria. RESULTS: We enrolled 426 (SVO: 310 vs. ESUS: 116) patients who met the inclusion criteria. In the 24-h Holter monitoring parameters, total number of PACs and PAC-to-total beat ratio were not significantly different between the two groups. However, NSATs were more frequent, and the duration of the longest NSAT was longer in the ESUS group. Multivariate logistic regression revealed that high brain natriuretic peptide levels, presence of NSAT, history of previous stroke, and the longest NSAT duration significantly correlated with the ESUS etiology. CONCLUSION: The presence of NSAT and its duration are more important indicators of embolic stroke than the frequency of PACs is. Therefore, considering secondary prevention in AIS patients with ESUS, 24-h Holter monitoring parameters, such as the presence of NSAT and its duration, could be considered as potential sources of cardio-embolism.


Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular Embólico , Embolia Intracraneal , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Electrocardiografía Ambulatoria/efectos adversos , Accidente Cerebrovascular Embólico/complicaciones , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Taquicardia/complicaciones , Factores de Riesgo , Embolia Intracraneal/complicaciones , Embolia Intracraneal/diagnóstico
18.
Int J Stroke ; 18(7): 812-820, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36748980

RESUMEN

BACKGROUND: Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown. AIMS: This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes. METHODS: We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores. RESULTS: Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23-0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19-0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31-21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups. CONCLUSION: This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.


Asunto(s)
Aterosclerosis , Fibrilación Atrial , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Fibrinolíticos/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/prevención & control , Constricción Patológica , Resultado del Tratamiento , Factores de Riesgo , Inhibidores de Agregación Plaquetaria/efectos adversos , Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Aterosclerosis/complicaciones , Aterosclerosis/tratamiento farmacológico , Arterias , Administración Oral
19.
JAMA Netw Open ; 6(2): e230524, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36821110

RESUMEN

Importance: An accurate and robust artificial intelligence (AI) algorithm for detecting cancer in digital breast tomosynthesis (DBT) could significantly improve detection accuracy and reduce health care costs worldwide. Objectives: To make training and evaluation data for the development of AI algorithms for DBT analysis available, to develop well-defined benchmarks, and to create publicly available code for existing methods. Design, Setting, and Participants: This diagnostic study is based on a multi-institutional international grand challenge in which research teams developed algorithms to detect lesions in DBT. A data set of 22 032 reconstructed DBT volumes was made available to research teams. Phase 1, in which teams were provided 700 scans from the training set, 120 from the validation set, and 180 from the test set, took place from December 2020 to January 2021, and phase 2, in which teams were given the full data set, took place from May to July 2021. Main Outcomes and Measures: The overall performance was evaluated by mean sensitivity for biopsied lesions using only DBT volumes with biopsied lesions; ties were broken by including all DBT volumes. Results: A total of 8 teams participated in the challenge. The team with the highest mean sensitivity for biopsied lesions was the NYU B-Team, with 0.957 (95% CI, 0.924-0.984), and the second-place team, ZeDuS, had a mean sensitivity of 0.926 (95% CI, 0.881-0.964). When the results were aggregated, the mean sensitivity for all submitted algorithms was 0.879; for only those who participated in phase 2, it was 0.926. Conclusions and Relevance: In this diagnostic study, an international competition produced algorithms with high sensitivity for using AI to detect lesions on DBT images. A standardized performance benchmark for the detection task using publicly available clinical imaging data was released, with detailed descriptions and analyses of submitted algorithms accompanied by a public release of their predictions and code for selected methods. These resources will serve as a foundation for future research on computer-assisted diagnosis methods for DBT, significantly lowering the barrier of entry for new researchers.


Asunto(s)
Inteligencia Artificial , Neoplasias de la Mama , Humanos , Femenino , Benchmarking , Mamografía/métodos , Algoritmos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Neoplasias de la Mama/diagnóstico por imagen
20.
J Robot Surg ; 17(4): 1421-1427, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36715965

RESUMEN

This study aimed to review the surgical outcomes of supracervical hysterectomy using the da Vinci SP® surgical system and conventional single-site laparoscopic surgery for uterine fibroids. This study included 79 patients who underwent supracervical hysterectomy with the da Vinci SP® surgical system and conventional single-site laparoscopy for uterine fibroid between June 2018 and April 2021. All the surgeries were performed by an experienced surgeon. Surgical outcomes and complications were reviewed in both groups. No significant difference was found between the two groups with regards to the patients' preoperative surgical conditions such as weight of the uterus, history of pelvic surgery, and pelvic adhesion. A significantly longer operation time (p < 0.01) and higher levels of C-reactive protein (p < 0.01) were found in the robotic surgery group; in particular, the uterus-out time was significantly longer (p < 0.01). No significant differences were found in other surgical outcomes such as complication rates and hospital stays. Supracervical hysterectomy using the da Vinci® SP surgical system is comparable to conventional single-site laparoscopy in uncomplicated cases. However, it requires a significantly longer operative time and has a higher inflammatory response.


Asunto(s)
Laparoscopía , Leiomioma , Procedimientos Quirúrgicos Robotizados , Femenino , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Histerectomía , Leiomioma/cirugía , Útero/cirugía , Estudios Retrospectivos
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