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1.
Artículo en Inglés | MEDLINE | ID: mdl-38431223

RESUMEN

BACKGROUND & AIMS: Colonoscopic surveillance is recommended in patients with colonic inflammatory bowel disease (IBD) given their increased risk of colorectal cancer (CRC). We aimed to develop and validate a dynamic prediction model for the occurrence of advanced colorectal neoplasia (aCRN, including high-grade dysplasia and CRC) in IBD. METHODS: We pooled data from 6 existing cohort studies from Canada, The Netherlands, the United Kingdom, and the United States. Patients with IBD and an indication for CRC surveillance were included if they underwent at least 1 follow-up procedure. Exclusion criteria included prior aCRN, prior colectomy, or an unclear indication for surveillance. Predictor variables were selected based on the literature. A dynamic prediction model was developed using a landmarking approach based on Cox proportional hazard modeling. Model performance was assessed with Harrell's concordance-statistic (discrimination) and by calibration curves. Generalizability across surveillance cohorts was evaluated by internal-external cross-validation. RESULTS: The surveillance cohorts comprised 3731 patients, enrolled and followed-up in the time period from 1973 to 2021, with a median follow-up period of 5.7 years (26,336 patient-years of follow-up evaluation); 146 individuals were diagnosed with aCRN. The model contained 8 predictors, with a cross-validation median concordance statistic of 0.74 and 0.75 for a 5- and 10-year prediction window, respectively. Calibration plots showed good calibration. Internal-external cross-validation results showed medium discrimination and reasonable to good calibration. CONCLUSIONS: The new prediction model showed good discrimination and calibration, however, generalizability results varied. Future research should focus on formal external validation and relate predicted aCRN risks to surveillance intervals before clinical application.

2.
J Intern Med ; 296(1): 68-79, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38659304

RESUMEN

BACKGROUND: The prevalence of metastatic pheochromocytoma and paraganglioma (PPGL) is approximately 15%-20%. Although there are indicators to assess metastatic risks, none of them predict metastasis reliably. Therefore, we aimed to develop and validate a scoring system using clinical, genetic, and biochemical risk factors to preoperatively predict the metastatic risk of PPGL. METHODS: In the cross-sectional cohort (n = 180), clinical, genetic, and biochemical risk factors for metastasis were identified using multivariate logistic regression analysis, and a novel scoring system was developed. The scoring system was validated and compared with the age, size of tumor, extra-adrenal location, and secretory type (ASES) score in the longitudinal cohort (n = 114). RESULTS: In the cross-sectional cohort, pseudohypoxia group-related gene variants (SDHB, SDHD, or VHL), methoxytyramine >0.16 nmol/L, and tumor size >6.0 cm were independently associated with metastasis after multivariate logistic regression. Using them, the gene variant, methoxytyramine, and size of tumor (GMS) score were developed. In the longitudinal cohort, Harrell's concordance index of the GMS score (0.873, 95% confidence interval [CI]: 0.738-0.941) was higher than that of the ASES score (0.713, 95% CI: 0.567-0.814, p = 0.007). In the longitudinal cohort, a GMS score ≥2 was significantly associated with a higher risk of metastasis (hazard ratio = 25.07, 95% CI: 5.65-111.20). A GMS score ≥2 (p < 0.001), but not ASES score ≥2 (p = 0.090), was associated with shorter progression-free survival. CONCLUSION: The GMS scoring system, which integrates gene variant, methoxytyramine level, and tumor size, provides a valuable preoperative approach to assess metastatic risk in PPGL.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Biomarcadores de Tumor , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/genética , Feocromocitoma/patología , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/patología , Masculino , Femenino , Persona de Mediana Edad , Paraganglioma/genética , Paraganglioma/patología , Estudios Transversales , Adulto , Biomarcadores de Tumor/genética , Succinato Deshidrogenasa/genética , Factores de Riesgo , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Estudios de Cohortes , Metanefrina/orina , Metanefrina/sangre , Estudios Longitudinales , Metástasis de la Neoplasia , Anciano , Carga Tumoral , Dopamina/análogos & derivados
3.
Oncology ; 102(1): 67-75, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37527640

RESUMEN

INTRODUCTION: Altered lipid metabolism has been reported to be associated with prognosis in multiple cancers. This study aimed to investigate the association of polymorphisms in lipid metabolism pathway genes with survival outcomes in patients with surgically resected non-small cell lung cancer (NSCLC). METHODS: In total, 744 patients with surgically resected NSCLC (380 in the discovery cohort and 364 in the validation cohort) were included in this study. The association between 176 polymorphisms of lipid metabolism pathway genes and the clinical outcomes of NSCLC patients was analyzed. RESULTS: Among the polymorphisms investigated, ACADSB rs10902859G>A was associated with significantly better overall survival (OS) in the discovery, validation, and combined cohorts. ACADSB rs10902859G>A was located in the repressed region and had strong linkage disequilibrium (D' = 1.00 and r2 = 0.94), with rs12220683G>C located in the H3K4me3 peak region, which indicates the presence of active promoters. ACADSB rs12220683G>C was also associated with better OS in the discovery, validation, and combined cohorts (in a dominant model; adjusted hazard ratio [aHR] = 0.53, 95% confidence interval [CI] = 0.30-0.94, p = 0.03; aHR = 0.37, 95% CI = 0.15-0.89, p = 0.03; and aHR = 0.47, 95% CI = 0.29-0.75, p = 0.002, respectively). In vitro luciferase assay demonstrated that the promoter activity of ACADSB was significantly increased in the rs12220683 variant C allele compared with that in the wild G allele (p = 3 × 10-5). CONCLUSION: These results suggest that ACADSB rs12220683G>C increases promoter activity and that increased ACADSB expression may result in better OS in patients with surgically resected NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/genética , Metabolismo de los Lípidos/genética , Genotipo , Polimorfismo de Nucleótido Simple , Pronóstico
4.
Eur Radiol ; 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755438

RESUMEN

OBJECTIVES: To compare the diagnostic performance and image quality of dual-energy computed tomography (DECT) with electron density (ED) image reconstruction with those of DECT with standard CT (SC) and virtual non-calcium (VNCa) image reconstructions, for diagnosing lumbar disc herniation (L-HIVD). METHODS: A total of 59 patients (354 intervertebral discs from T12/L1 to L5/S1; mean age, 60 years; 30 women and 29 men) who underwent DECT with spectral reconstruction and 3-T MRI within 2 weeks were enrolled between March 2021 and February 2022. Four radiologists independently assessed three image sets of randomized ED, SC, and VNCa images to detect L-HIVD at 8-week intervals. The coefficient of variance (CV) and the Weber contrast of the ROIs in the normal and diseased disc to cerebrospinal fluid space (NCR-normal/-diseased, respectively) were calculated to compare the image qualities of the noiseless ED and other series. RESULTS: Overall, 129 L-HIVDs were noted on MRI. In the detection of L-HIVD, ED showed a higher AUC and sensitivity than SC and VNCa; 0.871 vs 0.807 vs 833 (p = 0.002) and 81% vs 70% vs 74% (p = 0.006 for SC), respectively. CV was much lower in all measurements of ED than those for SC and VNCa (p < 0.001). Furthermore, NCR-normal and NCR-diseased were the highest in ED (ED vs SC in NCR-normal and NCR-diseased, p = 0.001 and p = 0.004, respectively; ED vs VNCa in NCR-diseased, p = 0.044). CONCLUSION: Compared to SC and VNCa images, DECT with ED reconstruction can enhance the AUC and sensitivity of L-HIVD detection with a lower CV and higher NCR. CLINICAL RELEVANCE STATEMENT: To our knowledge, this is the first study to quantify the image quality of noiseless ED images. ED imaging may be helpful for detecting L-HIVD in patients who cannot undergo MRI. KEY POINTS: ED images have diagnostic potential, but relevant quantitative analyses of image quality are limited. ED images detect disc herniation, with a better coefficient of variance and normalized contrast ratio values. ED images could detect L-HIVD when MRI is not an option.

5.
Cereb Cortex ; 33(8): 4779-4793, 2023 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-36169576

RESUMEN

A microdeletion of approximately 2.4 Mb at the 8p23 terminal region has been identified in a Taiwanese autistic boy. Among the products transcribed/translated from genes mapped in this region, the reduction of DLGAP2, a postsynaptic scaffold protein, might be involved in the pathogenesis of autism spectrum disorder (ASD). DLGAP2 protein was detected in the hippocampus yet abolished in homozygous Dlgap2 knockout (Dlgap2 KO) mice. In this study, we characterized the hippocampal phenotypes in Dlgap2 mutant mice. Dlgap2 KO mice exhibited impaired spatial memory, indicating poor hippocampal function in the absence of DLGAP2. Aberrant expressions of postsynaptic proteins, including PSD95, SHANK3, HOMER1, GluN2A, GluR2, mGluR1, mGluR5, ßCAMKII, ERK1/2, ARC, BDNF, were noticed in Dlgap2 mutant mice. Further, the spine density was increased in Dlgap2 KO mice, while the ratio of mushroom-type spines was decreased. We also observed a thinner postsynaptic density thickness in Dlgap2 KO mice at the ultrastructural level. These structural changes found in the hippocampus of Dlgap2 KO mice might be linked to impaired hippocampus-related cognitive functions such as spatial memory. Mice with Dlgap2 deficiency, showing signs of intellectual disability, a common co-occurring condition in patients with ASD, could be a promising animal model which may advance our understanding of ASD.


Asunto(s)
Trastorno del Espectro Autista , Animales , Ratones , Espinas Dendríticas/metabolismo , Hipocampo/metabolismo , Trastornos de la Memoria , Ratones Noqueados , Proteínas de Microfilamentos/metabolismo , Modelos Genéticos , Proteínas del Tejido Nervioso/metabolismo , Memoria Espacial , Columna Vertebral/metabolismo , Sinapsis/metabolismo
6.
Respiration ; 103(5): 257-267, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38499001

RESUMEN

INTRODUCTION: Data on factors related to mortality in patients with bronchiectasis exacerbation are insufficient. Computed tomography (CT) can measure the pectoralis muscle area (PMA) and is a useful tool to diagnose sarcopenia. This study aimed to evaluate whether PMA can predict mortality in patients with bronchiectasis exacerbation. METHODS: Patients hospitalized due to bronchiectasis exacerbation at a single center were retrospectively divided into survivors and non-survivors based on 1-year mortality. Thereafter, a comparison of the clinical and radiologic characteristics was conducted between the two groups. RESULTS: A total of 66 (14%) patients died at 1 year. In the multivariate analysis, age, BMI <18.4 kg/m2, sex-specific PMA quartile, ≥3 exacerbations in the previous year, serum albumin <3.5 g/dL, cystic bronchiectasis, tuberculosis-destroyed lung, and diabetes mellitus were independent predictors for the 1-year mortality in patients hospitalized with bronchiectasis exacerbation. A lower PMA was associated with a lower overall survival rate in the survival analysis according to sex-specific quartiles of PMA. PMA had the highest area under the curve during assessment of prognostic performance in predicting the 1-year mortality. The lowest sex-specific PMA quartile group exhibited higher disease severity than the highest quartile group. CONCLUSIONS: CT-derived PMA was an independent predictor of 1-year mortality in patients hospitalized with bronchiectasis exacerbation. Patients with lower PMA exhibited higher disease severity. These findings suggest that PMA might be a useful marker for providing additional information regarding prognosis of patients with bronchiectasis exacerbation.


Asunto(s)
Bronquiectasia , Progresión de la Enfermedad , Músculos Pectorales , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Bronquiectasia/mortalidad , Bronquiectasia/diagnóstico por imagen , Anciano , Músculos Pectorales/diagnóstico por imagen , Estudios Retrospectivos , Persona de Mediana Edad , Hospitalización , Sarcopenia/diagnóstico por imagen , Sarcopenia/mortalidad , Sarcopenia/diagnóstico , Pronóstico
7.
J Med Ethics ; 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38413189

RESUMEN

This paper examines the institutional mechanisms supporting the ethical oversight of human participant research conducted by the United Nations (UN). The UN has served an instrumental role in shaping international standards on research ethics, which invariably require ethical oversight of all research studies with human participants. The authors' experiences of conducting research collaboratively with UN agencies, in contrast, have led to concern that the UN frequently sponsors, or participates in, studies with human participants that have not received appropriate ethical oversight. It is argued that the institutional mechanisms in place to prevent research with human participants from being undertaken by the UN without ethical oversight do not, at present, extend substantively beyond the provision of guidelines and online training offered by a minority of UN bodies. The WHO and UNICEF are identified as notable exceptions, having implemented various measures to prevent health research with human participants from being undertaken without ethical oversight. Yet, it is highlighted that the WHO and UNICEF are not the only UN bodies that undertake health research with human participants and there are countless actors under the umbrella of the UN system that are regularly involved in non-health research with human participants. Arguments for the pursuit of the highest standard of ethical oversight by UN bodies are presented. Moving forward, the paper asks the question: is it time for the UN to set the standards for the oversight of ethical oversight?

8.
J Korean Med Sci ; 39(20): e159, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38804009

RESUMEN

Anatomy is a foundational subject in medicine and serves as its language. Hippocrates highlighted its importance, while Herophilus pioneered human dissection, earning him the title of the founder of anatomy. Vesalius later established modern anatomy, which has since evolved historically. In Korea, formal anatomy education for medical training began with the introduction of Western medicine during the late Joseon Dynasty. Before and after the Japanese occupation, anatomy education was conducted in the German style, and after liberation, it was maintained and developed by a small number of domestic anatomists. Medicine in Korea has grown alongside the country's rapid economic and social development. Today, 40 medical colleges produce world-class doctors to provide the best medical care service in the country. However, the societal demand for more doctors is growing in order to proactively address to challenges such as public healthcare issues, essential healthcare provision, regional medical service disparities, and an aging population. This study examines the history, current state, and challenges of anatomy education in Korea, emphasizing the availability of medical educators, support staff, and cadavers for gross anatomy instruction. While variations exist between Seoul and provincial medical colleges, each manages to deliver adequate education under challenging conditions. However, the rapid increase in medical student enrollment threatens to strain existing anatomy education resources, potentially compromising educational quality. To address these concerns, we propose strategies for training qualified gross anatomy educators, ensuring a sustainable cadaver supply, and enhancing infrastructure.


Asunto(s)
Anatomía , Educación Médica , Humanos , Anatomía/educación , Cadáver , Educación Médica/historia , Educación Médica/métodos , Educación Médica/tendencias , Historia del Siglo XX , República de Corea , Facultades de Medicina/historia , Facultades de Medicina/tendencias
9.
Int J Mol Sci ; 25(5)2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38474182

RESUMEN

Blocking the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim of this study was to explore the efficacy of TCM treatments against SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. Antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis (S. baicalensis) was found to be effective against SARS-CoV-2 infection, as it mediated the interaction between the viral spike protein and the hACE2 protein. Moreover, the active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside found in S. baicalensis, respectively, exhibited strong inhibitory activities targeting the viral spike protein and the hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors from S. baicalensis that mediate the interaction between the Omicron spike protein and the hACE2 receptor. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed.


Asunto(s)
COVID-19 , Flavonas , Humanos , SARS-CoV-2 , Scutellaria baicalensis , Glicoproteína de la Espiga del Coronavirus , Angiotensinas , Unión Proteica
10.
Thorax ; 78(11): 1080-1089, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37495367

RESUMEN

BACKGROUND: Diet has a crucial role in the gut microbiota, and dysbiosis in the gut and lungs has been suggested to be associated with chronic obstructive pulmonary disease. We compared the diet, microbiome and metabolome between asymptomatic smokers and those with emphysema. METHODS: We enrolled 10 asymptomatic smokers with preserved lung function and 16 smokers with emphysema with severe airflow limitation. Dietary intake information was gathered by a self-reported questionnaire. Sputum and faecal samples were collected for microbial and metabolomics analysis. A murine model of emphysema was used to determine the effect of metabolite supplementation. RESULTS: Despite having a similar smoking history with emphysema patients, asymptomatic smokers had higher values of body mass index, fibre intake and faecal acetate level. Linear discriminant analysis identified 17 microbial taxonomic members that were relatively enriched in the faeces of asymptomatic smokers. Analysis of similarity results showed dissimilarity between the two groups (r=0.287, p=0.003). Higher acetate level was positively associated with forced expiratory volume in one second in the emphysema group (r=0.628, p=0.012). Asymptomatic smokers had a greater number of species associated with acetate and propionate (r>0.6) than did those with emphysema (30 vs 19). In an emphysema mouse model, supplementation of acetate and propionate reduced alveolar destruction and the production of proinflammatory cytokines, and propionate decreased the CD3+CD4+IL-17+ T-cell population in the lung and spleen. CONCLUSION: Smokers with emphysema showed differences in diet, microbiome and short-chain fatty acids compared with asymptomatic smokers. Acetate and propionate showed therapeutic effects in a smoking-induced murine model of emphysema.


Asunto(s)
Enfisema , Microbioma Gastrointestinal , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Animales , Ratones , Fumadores , Propionatos , Modelos Animales de Enfermedad , Volumen Espiratorio Forzado , Enfisema/complicaciones , Acetatos
11.
J Gene Med ; 25(12): e3564, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37434327

RESUMEN

BACKGROUND: Adenovirus expresses two non-coding virus-associated (VA) RNAs: VA I RNA and VA II RNA. Adenovirus-expressed VA RNAs interfere with the microRNA (miRNA) pathway by competing with precursor miRNAs. The processing pattern of primary miRNA (pri-miRNA) and factors to affect its processing are not exactly known when using adenovirus for the delivery of pri-miRNA. METHODS: To observe pri-miRNA processing, plasmid construct encoding pri-miRNA was co-transfected with VA I/II RNA expression plasmid, or recombinant adenovirus encoding pri-miRNA was generated and infected. Levels of miRNAs, VA I RNA and VA II RNA were analyzed by a quantitative real-time PCR (RT-PCR). VA I-II full-length RNA was analyzed by a RT-PCR. RNA immunoprecipitation analysis to pull-down the VA I-II full-length RNA binding with Drosha was conducted with Drosha antibody. RESULTS: pri-miRNA was normally processed into mature miRNA when it was expressed in cells using plasmid. However, miRNA maturation was impaired when pri-miRNA was delivered and expressed using adenovirus. Of note, pri-miRNA processing was observed to be blocked by VA RNA expression. Such blocked processing could be recovered by introducing antisense RNA of VA RNA, anti-3'VA RNA. In addition, VA RNAs were transcribed into VA I-II full-length RNA, which was found to bind and sequester Drosha. CONCLUSIONS: Adenovirus infection downregulated the processing of pri-miRNAs in cells, and such downregulation could be derived from VA I-II full-length RNAs in pri-miRNA-like form through competitively binding to Drosha protein. These results indicated that the expression of adenovirus VA RNAs should be inhibited for successful delivery and expression of pri-miRNA or shRNA in cells using adenovirus.


Asunto(s)
MicroARNs , Procesamiento Postranscripcional del ARN , MicroARNs/genética , MicroARNs/metabolismo , ARN Viral/genética , ARN Viral/metabolismo , Adenoviridae/genética
12.
Nat Methods ; 17(6): 609-613, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32424271

RESUMEN

We developed entangled link-augmented stretchable tissue-hydrogel (ELAST), a technology that transforms tissues into elastic hydrogels to enhance macromolecular accessibility and mechanical stability simultaneously. ELASTicized tissues are highly stretchable and compressible, which enables reversible shape transformation and faster delivery of probes into intact tissue specimens via mechanical thinning. This universal platform may facilitate rapid and scalable molecular phenotyping of large-scale biological systems, such as human organs.


Asunto(s)
Hidrogeles/química , Coloración y Etiquetado/métodos , Ingeniería de Tejidos/métodos , Acrilamida/química , Animales , Fenómenos Biomecánicos , Materiales Biomiméticos/química , Bioimpresión , Corteza Cerebral/química , Reactivos de Enlaces Cruzados/química , Módulo de Elasticidad , Hipocampo/química , Humanos , Ensayo de Materiales , Ratones , Estrés Mecánico , Resistencia a la Tracción
13.
Plant Cell Environ ; 46(4): 1157-1175, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36071575

RESUMEN

Auxin is well known to stimulate coleoptile elongation and rapid seedling growth in the air. However, its role in regulating rice germination and seedling establishment under submergence is largely unknown. Previous studies revealed that excessive levels of indole-3-acetic acid(IAA) frequently cause the inhibition of plant growth and development. In this study, the high-level accumulation of endogenous IAA is observed under dark submergence, stimulating rice coleoptile elongation but limiting the root and primary leaf growth during anaerobic germination (AG). We found that oxygen and light can reduce IAA levels, promote the seedling establishment and enhance rice AG tolerance. miRNA microarray profiling and RNA gel blot analysis results show that the expression of miR167 is negatively regulated by submergence; it subsequently modulates the accumulation of free IAA through the miR167-ARF-GH3 pathway. The OsGH3-8 encodes an IAA-amido synthetase that functions to prevent free IAA accumulation. Reduced miR167 levels or overexpressing OsGH3-8 increase auxin metabolism, reduce endogenous levels of free IAA and enhance rice AG tolerance. Our studies reveal that poor seed germination and seedling growth inhibition resulting from excessive IAA accumulation would cause intolerance to submergence in rice, suggesting that a certain threshold level of auxin is essential for rice AG tolerance.


Asunto(s)
Germinación , Oryza , Plantones/metabolismo , Oryza/genética , Anaerobiosis , Proteínas de Plantas/metabolismo , Ácidos Indolacéticos/metabolismo , Regulación de la Expresión Génica de las Plantas
14.
Oncology ; 101(2): 96-104, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36257285

RESUMEN

OBJECTIVE: This study was conducted to investigate the association between genetic variants in histone modification regions and clinical outcomes of PEM chemotherapy in patients with lung adenocarcinoma. METHODS: Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The associations of 279 SNPs with chemotherapy response and overall survival (OS) were analyzed in 314 lung adenocarcinoma patients who underwent PEM chemotherapy. RESULTS: Among the SNPs investigated, 18 were significantly associated with response to chemotherapy, while 28 with OS. Of these SNPs, rs549794A>G in an enhancer which is expected to regulate the expression of ribosomal protein S3 (RPS3) gene was significantly associated with both worse response to chemotherapy and worse OS (adjusted odds ratio = 0.59, 95% CI = 0.36-0.97, p = 0.04; adjusted hazard ratio = 1.44, 95% CI = 1.09-1.91, p = 0.01, respectively). Previous studies suggested that RPS3, a multi-functional protein with various extraribosomal activities, may play a role in chemotherapy resistance. Therefore, it is postulated that rs549794-induced change in the expression level of RPS3 may affect the response to PEM chemotherapy and consequently the survival outcomes in lung adenocarcinoma patients. CONCLUSION: This study suggests that genetic variants in the histone modification regions may be useful for the prediction of clinical outcomes of PEM chemotherapy in advanced lung adenocarcinoma.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Pemetrexed/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Código de Histonas , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
15.
BMC Cancer ; 23(1): 1100, 2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-37953261

RESUMEN

BACKGROUND: Accurate determination of microsatellite instability (MSI) status is critical for optimal treatment in cancer patients. Conventional MSI markers can sometimes display subtle shifts that are difficult to interpret, especially in non-colorectal cases. We evaluated an experimental eight marker-panel including long mononucleotide repeat (LMR) markers for detection of MSI. METHODS: The eight marker-panel was comprised of five conventional markers (BAT-25, BAT-26, NR-21, NR-24, and NR-27) and three LMR markers (BAT-52, BAT-59 and BAT-62). MSI testing was performed against 300 specimens of colorectal, gastric, and endometrial cancers through PCR followed by capillary electrophoresis length analysis. RESULTS: The MSI testing with eight marker-panel showed 99.3% (295/297) concordance with IHC analysis excluding 3 MMR-focal deficient cases. The sensitivity of BAT-59 and BAT-62 was higher than or comparable to that of conventional markers in gastric and endometrial cancer. The mean shift size was larger in LMR markers compared to conventional markers for gastric and endometrial cancers. CONCLUSIONS: The MSI testing with eight maker-panel showed comparable performance with IHC analysis. The LMR markers, especially BAT-59 and BAT-62, showed high sensitivity and large shifts which can contribute to increased confidence in MSI classification, especially in gastric and endometrial cancers. Further study is needed with large number of samples for the validation of these LMR markers.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Endometriales , Femenino , Humanos , Inestabilidad de Microsatélites , Repeticiones de Microsatélite/genética , Neoplasias Colorrectales/genética , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética
16.
Int Microbiol ; 2023 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-38001399

RESUMEN

Lactic acid bacteria (LAB) that metabolize sugars to obtain energy and produce a large amount of lactate through the process are well known for their benefits. However, they can be used on a large scale only when good storage stability is guaranteed. The vitality and stability of several LAB strains were effectively protected in this investigation by L-theanine at 1% of the appropriate concentration (Lactiplantibacillus plantarum MG5023, Enterococcus faecium MG5232, Lactococcus lactis MG4668, Streptococcus thermophilus MG5140, and Bifidobacterium animalis subsp. lactis MG741). The inclusion of L-theanine as a protective agent significantly enhanced the viability of all strains throughout the freeze-drying process compared to that of the non-coated probiotics. The efficacy of L-theanine in improving bacterial stability and survivability was evaluated using accelerated stability tests, gastrointestinal (GI) tract survivability tests, and adhesion assays with intestinal epithelial cells. The cell surface was covered with substances including L-theanine, according to morphological findings, providing efficient defense against a variety of external stresses. Therefore, by exerting anti-freezing and anti-thawing properties, the adoption of L-theanine as a new and efficient protective agent may improve the stability and viability of a variety of probiotics.

17.
Int Microbiol ; 26(3): 563-577, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36646920

RESUMEN

BACKGROUND: Concerns regarding antimicrobial resistance (AMR) have resulted in the World Health Organization (WHO) designating so-called global priority pathogens (GPPs). However, little discussion has focused on the diagnosis of GPPs. To enable the simultaneous identification of pathogens and AMR, we developed a modular real-time nucleic acid amplification test (MRT-NAAT). METHODS: Sequence-specific primers for each modular unit for MRT-NAAT pathogen identification and AMR sets were designed. The composition of the reaction mixture and the real-time PCR program were unified irrespective of primer type so to give MRT-NAAT modularity. Standard strains and clinical isolates were used to evaluate the performance of MRT-NAAT by real-time PCR and melting curve analysis. Probit analysis for the MRT-NAAT pathogen identification set was used to assess the limit of detection (LoD). RESULTS: The MRT-NAAT pathogen identification set was made up of 15 modular units 109-199 bp in product size and with a Tms of 75.5-87.5 °C. The LoD was < 15.548 fg/µL, and nine modular units successfully detected the target pathogens. The MRT-NAAT AMR set included 24 modular units 65-785 bp in product size with a Tms of 75.5-87.5 °C; it showed high performance for detecting GPP target genes and variants. CONCLUSIONS: MRT-NAAT enables pathogen identification and AMR gene detection and is time-effective. By unifying the reaction settings of each modular unit, the modularity where combinations of primers can be used according to need could be achieved. This would greatly help in reflecting the researcher's need and the AMR status of a certain region while successfully detecting pathogens and AMR genes.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Organización Mundial de la Salud , Pruebas Diagnósticas de Rutina
18.
Eur Radiol ; 33(7): 4782-4788, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36645456

RESUMEN

OBJECTIVES: We investigated the correlation of aponeurotic expansion of the supraspinatus tendon (AESST) with shoulder pathologies such as long head of biceps tendon (LHB), supraspinatus tendon (SST), and subscapularis tendon (SSc). METHODS: We retrospectively evaluated 47 healthy patients and 163 patients with shoulder symptoms from August 2014 to March 2021. First, the presence of AESST was evaluated based on Moser et al.'s classification. Second, the presence of abnormal findings of including LHB tendinitis, LHB subluxation, SST tendinitis, SST tear, SSc tendinitis, and SSc tendon tear was evaluated. We analyzed the prevalence and type of AESST between the two study groups and the relationship between abnormal findings and the presence of AESST. RESULTS: The prevalence of AESST for readers 1 and 2 was 26.1% and 30.4% in the asymptomatic group, respectively, and 22.8% and 31.3% in the symptomatic group. Type 1 was most common (17.3-23.9%) followed by types 2a and 2b. There were no significant differences in the distribution of aponeurosis type between the two groups. In the AESST-positive groups, 45.9% and 47.1% had SST tears on examination by readers 1 and 2, respectively, whereas only 26.4% and 27.9% had SST tears in the AESST-negative group suggesting AESST is associated with SST tear. The odds ratio for SST tear in the presence of AESST was 2.370 and 2.294 (readers 1 and 2). CONCLUSIONS: There is an association between SST tears and the presence of AESST. KEY POINTS: • We evaluated the prevalence of aponeurotic expansion of the supraspinatus tendon (AESST) on MR imaging by type in both symptomatic and asymptomatic groups. • We investigated the correlation of AESST with shoulder pathologies such as biceps tendon and supraspinatus tendon tears. • There is an association between SST tears and the presence of AESST. • Radiologists should be aware of the risk of rotator cuff pathology if AESST is detected.


Asunto(s)
Lesiones del Manguito de los Rotadores , Tendinopatía , Traumatismos de los Tendones , Humanos , Manguito de los Rotadores/patología , Hombro , Traumatismos de los Tendones/diagnóstico por imagen , Traumatismos de los Tendones/epidemiología , Estudios Retrospectivos , Aponeurosis/patología , Lesiones del Manguito de los Rotadores/complicaciones , Lesiones del Manguito de los Rotadores/diagnóstico por imagen , Lesiones del Manguito de los Rotadores/epidemiología , Tendones/patología , Rotura , Imagen por Resonancia Magnética/métodos , Tendinopatía/complicaciones , Tendinopatía/diagnóstico por imagen , Tendinopatía/epidemiología
19.
Extremophiles ; 27(3): 21, 2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37548679

RESUMEN

Halocins, the proteinaceous antimicrobial agents produced by haloarchaea, may be used for the preservation of salted foods and the treatment of diseases. For their application and function explanation, it is necessary to produce the active recombinants. In this work, a haloarchaeal strain producing halocin was isolated from the salt-fermented shrimp and identified as Natrinema sp. RNS21 by 16S rRNA gene sequence analysis. From 1 L of RNS21 culture, about 0.32 mg of halocin with 96% purity was obtained. Based on the molecular weight, stability and amino acid sequence alignment, the antimicrobial peptide belonged to the halocin C8 (HalC8) family. HalC8 was expressed by fusion with glutathione-S-transferase (GST) in E. coli, followed by affinity purification and enterokinase (EK) cleavage. About 6.2 mg of recombinant HalC8 with 95% purity was obtained from 1 L of E. coli culture. MALDI-TOF-MS and RP-HPLC analysis indicated that the molecular weight and folding pattern of purified recombinant HalC8 were the same as those of native HalC8. Recombinant HalC8 showed obvious inhibitory activity against Haloferax volcanii. Contrast to native HalC8, the active recombinant HalC8 could be easily produced in a short time with a high yield.


Asunto(s)
Escherichia coli , Halobacteriaceae , Escherichia coli/genética , Péptidos Antimicrobianos , ARN Ribosómico 16S , Halobacteriaceae/genética
20.
Nicotine Tob Res ; 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37947283

RESUMEN

INTRODUCTION: Instagram and TikTok, video-based social media platforms popular among adolescents, contain tobacco-related content despite the platforms' policies prohibiting substance-related posts. Prior research identified themes in e-cigarette-related social media posts using qualitative or text-based machine learning methods. We developed an image-based computer vision model to identify e-cigarette products in social media images and videos. METHODS: We created a dataset of 6,999 Instagram images labeled for 8 object classes: mod or pod devices, e-juice containers, packaging boxes, nicotine warning labels, e-juice flavors, e-cigarette brand names, and smoke clouds. We trained a DyHead object detection model using a Swin-Large backbone, evaluated the model's performance on 20 Instagram and TikTok videos, and applied the model to 14,072 e-cigarette-related promotional TikTok videos (2019-2022; 10,276,485 frames). RESULTS: The model achieved the following mean average precision scores on the image test set: e-juice container: 0.89; pod device: 0.67; mod device: 0.54; packaging box: 0.84; nicotine warning label: 0.86; e-cigarette brand name: 0.71; e-juice flavor name: 0.89; and smoke cloud: 0.46. The largest number of TikTok videos - 9,091 (65%) - contained smoke clouds, followed by mod and pod devices detected in 6,667 (47%) and 5,949 (42%) videos respectively. Prevalence of nicotine warning labels was the lowest, detected in 980 videos (7%). CONCLUSIONS: Deep learning-based object detection technology enables automated analysis of visual posts on social media. Our computer vision model can detect the presence of e-cigarettes products in images and videos, providing valuable surveillance data for tobacco regulatory science. IMPLICATIONS: Prior research identified themes in e-cigarette-related social media posts using qualitative or text-based machine learning methods. We developed an image-based computer vision model to identify e-cigarette products in social media images and videos.We trained a DyHead object detection model using a Swin-Large backbone, evaluated the model's performance on 20 Instagram and TikTok videos featuring at least two e-cigarette objects, and applied the model to 14,072 e-cigarette-related promotional TikTok videos (2019-2022; 10,276,485 frames).The deep learning model can be used for automated, scalable surveillance of image- and video-based e-cigarette-related promotional content on social media, providing valuable data for tobacco regulatory science. Social media platforms could use computer vision to identify tobacco-related imagery and remove it promptly, which could reduce adolescents' exposure to tobacco content online.

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