RESUMEN
Cone snail venoms contain a wide variety of bioactive peptides, including insulin-like molecules with distinct structural features, binding modes and biochemical properties. Here, we report an active humanized cone snail venom insulin with an elongated A chain and a truncated B chain, and use cryo-electron microscopy (cryo-EM) and protein engineering to elucidate its interactions with the human insulin receptor (IR) ectodomain. We reveal how an extended A chain can compensate for deletion of B-chain residues, which are essential for activity of human insulin but also compromise therapeutic utility by delaying dissolution from the site of subcutaneous injection. This finding suggests approaches to developing improved therapeutic insulins. Curiously, the receptor displays a continuum of conformations from the symmetric state to a highly asymmetric low-abundance structure that displays coordination of a single humanized venom insulin using elements from both of the previously characterized site 1 and site 2 interactions.
Asunto(s)
Insulina , Venenos de Moluscos , Microscopía por Crioelectrón , Humanos , Insulina/metabolismo , Venenos de Moluscos/química , Venenos de Moluscos/metabolismo , Péptidos , Conformación ProteicaRESUMEN
PURPOSE: The S2AI screw technique has several advantages over the conventional iliac screw fixation technique. However, connecting the S2AI screw head to the main rod is difficult due to its medial entry point. We introduce a new technique for connecting the S2AI screw head to a satellite rod and compare it with the conventional method of connecting the S2AI screw to the main rod. METHODS: Seventy-four patients who underwent S2AI fixation for degenerative sagittal imbalance and were followed up for ≥ 2 years were included. All the patients underwent long fusion from T9 or T10 to the pelvis. The S2AI screw head was connected to the satellite rod (SS group) in 43 patients and the main rod (SM group) in 31 patients. In the SS group, the satellite rod was placed medial to the main rod and connected by the S2AI screw and domino connectors. In the SM group, the main rod was connected directly to the S2AI screw head and supported by accessory rods. Radiographic and clinical outcomes were evaluated in both groups. RESULTS: There were no significant differences in postoperative complications, including proximal junctional failure, proximal junctional kyphosis, rod breakage, screw loosening, wound problems, and infection between the two groups. Furthermore, the correction power of sagittal deformity and clinical results in the SS group were comparable to those in the SM group. CONCLUSION: Connecting the S2AI screw to the satellite rod is a convenient method comparable to the conventional S2AI connection method in terms of radiological and clinical outcomes.
Asunto(s)
Tornillos Óseos , Fusión Vertebral , Humanos , Masculino , Femenino , Fusión Vertebral/métodos , Fusión Vertebral/instrumentación , Persona de Mediana Edad , Anciano , Ilion/cirugía , Ilion/diagnóstico por imagen , Resultado del Tratamiento , Adulto , Sacro/cirugía , Sacro/diagnóstico por imagenRESUMEN
BACKGROUND: Robust and accurate prediction of severity for patients with COVID-19 is crucial for patient triaging decisions. Many proposed models were prone to either high bias risk or low-to-moderate discrimination. Some also suffered from a lack of clinical interpretability and were developed based on early pandemic period data. Hence, there has been a compelling need for advancements in prediction models for better clinical applicability. OBJECTIVE: The primary objective of this study was to develop and validate a machine learning-based Robust and Interpretable Early Triaging Support (RIETS) system that predicts severity progression (involving any of the following events: intensive care unit admission, in-hospital death, mechanical ventilation required, or extracorporeal membrane oxygenation required) within 15 days upon hospitalization based on routinely available clinical and laboratory biomarkers. METHODS: We included data from 5945 hospitalized patients with COVID-19 from 19 hospitals in South Korea collected between January 2020 and August 2022. For model development and external validation, the whole data set was partitioned into 2 independent cohorts by stratified random cluster sampling according to hospital type (general and tertiary care) and geographical location (metropolitan and nonmetropolitan). Machine learning models were trained and internally validated through a cross-validation technique on the development cohort. They were externally validated using a bootstrapped sampling technique on the external validation cohort. The best-performing model was selected primarily based on the area under the receiver operating characteristic curve (AUROC), and its robustness was evaluated using bias risk assessment. For model interpretability, we used Shapley and patient clustering methods. RESULTS: Our final model, RIETS, was developed based on a deep neural network of 11 clinical and laboratory biomarkers that are readily available within the first day of hospitalization. The features predictive of severity included lactate dehydrogenase, age, absolute lymphocyte count, dyspnea, respiratory rate, diabetes mellitus, c-reactive protein, absolute neutrophil count, platelet count, white blood cell count, and saturation of peripheral oxygen. RIETS demonstrated excellent discrimination (AUROC=0.937; 95% CI 0.935-0.938) with high calibration (integrated calibration index=0.041), satisfied all the criteria of low bias risk in a risk assessment tool, and provided detailed interpretations of model parameters and patient clusters. In addition, RIETS showed potential for transportability across variant periods with its sustainable prediction on Omicron cases (AUROC=0.903, 95% CI 0.897-0.910). CONCLUSIONS: RIETS was developed and validated to assist early triaging by promptly predicting the severity of hospitalized patients with COVID-19. Its high performance with low bias risk ensures considerably reliable prediction. The use of a nationwide multicenter cohort in the model development and validation implicates generalizability. The use of routinely collected features may enable wide adaptability. Interpretations of model parameters and patients can promote clinical applicability. Together, we anticipate that RIETS will facilitate the patient triaging workflow and efficient resource allocation when incorporated into a routine clinical practice.
Asunto(s)
Algoritmos , COVID-19 , Triaje , Humanos , Biomarcadores , COVID-19/diagnóstico , Mortalidad Hospitalaria , Redes Neurales de la Computación , Triaje/métodos , República de CoreaRESUMEN
BACKGROUND: An artificial intelligence (AI) model using chest radiography (CXR) may provide good performance in making prognoses for COVID-19. OBJECTIVE: We aimed to develop and validate a prediction model using CXR based on an AI model and clinical variables to predict clinical outcomes in patients with COVID-19. METHODS: This retrospective longitudinal study included patients hospitalized for COVID-19 at multiple COVID-19 medical centers between February 2020 and October 2020. Patients at Boramae Medical Center were randomly classified into training, validation, and internal testing sets (at a ratio of 8:1:1, respectively). An AI model using initial CXR images as input, a logistic regression model using clinical information, and a combined model using the output of the AI model (as CXR score) and clinical information were developed and trained to predict hospital length of stay (LOS) ≤2 weeks, need for oxygen supplementation, and acute respiratory distress syndrome (ARDS). The models were externally validated in the Korean Imaging Cohort of COVID-19 data set for discrimination and calibration. RESULTS: The AI model using CXR and the logistic regression model using clinical variables were suboptimal to predict hospital LOS ≤2 weeks or the need for oxygen supplementation but performed acceptably in the prediction of ARDS (AI model area under the curve [AUC] 0.782, 95% CI 0.720-0.845; logistic regression model AUC 0.878, 95% CI 0.838-0.919). The combined model performed better in predicting the need for oxygen supplementation (AUC 0.704, 95% CI 0.646-0.762) and ARDS (AUC 0.890, 95% CI 0.853-0.928) compared to the CXR score alone. Both the AI and combined models showed good calibration for predicting ARDS (P=.079 and P=.859). CONCLUSIONS: The combined prediction model, comprising the CXR score and clinical information, was externally validated as having acceptable performance in predicting severe illness and excellent performance in predicting ARDS in patients with COVID-19.
Asunto(s)
COVID-19 , Aprendizaje Profundo , Síndrome de Dificultad Respiratoria , Humanos , Inteligencia Artificial , COVID-19/diagnóstico por imagen , Estudios Longitudinales , Estudios Retrospectivos , Radiografía , Oxígeno , PronósticoRESUMEN
[This corrects the article DOI: 10.2196/42717.].
RESUMEN
This corrects the article on p. e413 in vol. 35, PMID: 33258333.
RESUMEN
Multivalent O-antigen polysaccharide glycoconjugate vaccines are under development to prevent invasive infections caused by pathogenic Enterobacteriaceae. Sequence type 131 (ST131) Escherichia coli of serotype O25b has emerged as the predominant lineage causing invasive multidrug-resistant extraintestinal pathogenic E. coli (ExPEC) infections. We observed the prevalence of E. coli O25b ST131 among a contemporary collection of isolates from U.S. bloodstream infections from 2013 to 2016 (n = 444) and global urinary tract infections from 2014 to 2017 (n = 102) to be 25% and 24%, respectively. To maximize immunogenicity of the serotype O25b O antigen, we investigated glycoconjugate properties, including CRM197 carrier protein cross-linking (single-end versus cross-linked "lattice") and conjugation chemistry (reductive amination chemistry in dimethyl sulfoxide [RAC/DMSO] versus ((2-((2-oxoethyl)thio)ethyl)carbamate [eTEC] linker). Using opsonophagocytic assays (OPAs) to measure serum functional antibody responses to vaccination, we observed that higher-molecular-mass O25b long-chain lattice conjugates showed improved immunogenicity in mice compared with long- or short-chain O antigens conjugated via single-end attachment. The lattice conjugates protected mice from lethal challenge with acapsular O25b ST131 strains as well as against hypervirulent O25b isolates expressing K5 or K100 capsular polysaccharides. A single 1-µg dose of long-chain O25b lattice conjugate constructed with both chemistries also elicited robust serum IgG and OPA responses in cynomolgus macaques. Our findings show that key properties of the O-antigen carrier protein conjugate such as saccharide epitope density and degree of intermolecular cross-linking can significantly enhance functional immunogenicity.
Asunto(s)
Infecciones por Escherichia coli , Antígenos O , Animales , Proteínas Portadoras , Escherichia coli , Infecciones por Escherichia coli/prevención & control , Glicoconjugados , RatonesRESUMEN
Molecular glue degraders, such as lenalidomide and pomalidomide, bind to cereblon (CRBN) E3 ligase and subsequently recruit neosubstrate proteins, Ikaros (IKZF1) and Aiolos (IKZF3), for the ubiquitination-proteasomal degradation process. In this study, we explored structure-activity relationship analysis for novel GSPT1 degraders utilizing a benzotriazinone scaffold previously discovered as a novel CRBN binder. In particular, we focused on the position of the ureido group on the benzotriazinone scaffold, substituent effect on the phenylureido group, and methyl substitution on the benzylic position of benzotriazinone. As a result, we identified 34f (TD-522), which exhibits strong anti-proliferative effects in both KG-1 (EC50 = 0.5 nM) and TMD-8 (EC50 = 5.2 nM) cell lines. Compound 34f effectively induced GSPT1 degradation with a DC50 of 0.269 nM and Dmax of >95 % at 10 nM concentration in KG-1 cells. An in vivo xenograft study showed that compound 34f effectively suppressed TMD8-driven tumor growth, suggesting a potential role in the development of novel GSPT1 degraders.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Animales , Modelos Animales de Enfermedad , Xenoinjertos , Humanos , Lenalidomida/química , Lenalidomida/farmacología , Ratones , Proteolisis , Relación Estructura-ActividadRESUMEN
The ability to accurately predict the prognosis and intervention requirements for treating highly infectious diseases, such as COVID-19, can greatly support the effective management of patients, especially in resource-limited settings. The aim of the study is to develop and validate a multimodal artificial intelligence (AI) system using clinical findings, laboratory data and AI-interpreted features of chest X-rays (CXRs), and to predict the prognosis and the required interventions for patients diagnosed with COVID-19, using multi-center data. In total, 2282 real-time reverse transcriptase polymerase chain reaction-confirmed COVID-19 patients' initial clinical findings, laboratory data and CXRs were retrospectively collected from 13 medical centers in South Korea, between January 2020 and June 2021. The prognostic outcomes collected included intensive care unit (ICU) admission and in-hospital mortality. Intervention outcomes included the use of oxygen (O2) supplementation, mechanical ventilation and extracorporeal membrane oxygenation (ECMO). A deep learning algorithm detecting 10 common CXR abnormalities (DLAD-10) was used to infer the initial CXR taken. A random forest model with a quantile classifier was used to predict the prognostic and intervention outcomes, using multimodal data. The area under the receiver operating curve (AUROC) values for the single-modal model, using clinical findings, laboratory data and the outputs from DLAD-10, were 0.742 (95% confidence interval [CI], 0.696−0.788), 0.794 (0.745−0.843) and 0.770 (0.724−0.815), respectively. The AUROC of the combined model, using clinical findings, laboratory data and DLAD-10 outputs, was significantly higher at 0.854 (0.820−0.889) than that of all other models (p < 0.001, using DeLong's test). In the order of importance, age, dyspnea, consolidation and fever were significant clinical variables for prediction. The most predictive DLAD-10 output was consolidation. We have shown that a multimodal AI model can improve the performance of predicting both the prognosis and intervention in COVID-19 patients, and this could assist in effective treatment and subsequent resource management. Further, image feature extraction using an established AI engine with well-defined clinical outputs, and combining them with different modes of clinical data, could be a useful way of creating an understandable multimodal prediction model.
Asunto(s)
COVID-19 , Inteligencia Artificial , COVID-19/diagnóstico , COVID-19/terapia , Humanos , Unidades de Cuidados Intensivos , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: The diagnostic accuracies of the imaging studies should be clearly acknowledged in managing head and neck cancer patients; however, the accuracies of preoperative imaging studies in detecting retropharyngeal lymph node (RPLN) metastasis are still not clarified. This study was to evaluate diagnostic accuracies of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) in detecting RPLN metastasis of head and neck squamous cell carcinomas. METHODS: For 123 patients who had performed RPLN dissection during the surgery of their squamous cell carcinoma of the head and neck, preoperative CT, MRI, and/or PET-CT were reviewed for RPLN metastasis in a blinded fashion by one experienced radiologist. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of each imaging modality were assessed, by comparing with the histopathologic findings of the resected RPLNs that served as the standard of reference. RESULTS: RPLNs were pathologically positive for metastasis in 43 of the 123 patients (35%). Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy in detecting metastasis to RPLN were 65, 94, 85, 83, and 84% for CT; 74, 94, 87, 87 and 87% for MRI; 83, 93, 89, 89 and 89% for PET-CT, respectively. When all the three imaging modalities were considered together (n = 74), they offered sensitivity of 90%, specificity of 91%, positive predictive value of 87%, negative predictive value of 93%, and accuracy of 91%. CONCLUSIONS: The preoperative imaging studies offered relatively high specificity rates, but rather low sensitivity rates. The three imaging modalities altogether increased diagnostic accuracies, which highlights the potential of the three studies when used altogether can minimize missed diagnoses of RPLN metastasis.
Asunto(s)
Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Faringe/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Escisión del Ganglio Linfático , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Faringe/cirugía , Tomografía Computarizada por Tomografía de Emisión de Positrones , Periodo Preoperatorio , Sensibilidad y Especificidad , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The Korean Society of Thoracic Radiology (KSTR) recently constructed a nation-wide coronavirus disease 2019 (COVID-19) database and imaging repository, referred to the Korean imaging cohort of COVID-19 (KICC-19) based on the collaborative efforts of its members. The purpose of this study was to provide a summary of the clinico-epidemiological data and imaging data of the KICC-19. METHODS: The KSTR members at 17 COVID-19 referral centers retrospectively collected imaging data and clinical information of consecutive patients with reverse transcription polymerase chain reaction-proven COVID-19 in respiratory specimens from February 2020 through May 2020 who underwent diagnostic chest computed tomography (CT) or radiograph in each participating hospital. RESULTS: The cohort consisted of 239 men and 283 women (mean age, 52.3 years; age range, 11-97 years). Of the 522 subjects, 201 (38.5%) had an underlying disease. The most common symptoms were fever (n = 292) and cough (n = 245). The 151 patients (28.9%) had lymphocytopenia, 86 had (16.5%) thrombocytopenia, and 227 patients (43.5%) had an elevated CRP at admission. The 121 (23.4%) needed nasal oxygen therapy or mechanical ventilation (n = 38; 7.3%), and 49 patients (9.4%) were admitted to an intensive care unit. Although most patients had cured, 21 patients (4.0%) died. The 465 (89.1%) subjects underwent a low to standard-dose chest CT scan at least once during hospitalization, resulting in a total of 658 CT scans. The 497 subjects (95.2%) underwent chest radiography at least once during hospitalization, which resulted in a total of 1,475 chest radiographs. CONCLUSION: The KICC-19 was successfully established and comprised of 658 CT scans and 1,475 chest radiographs of 522 hospitalized Korean COVID-19 patients. The KICC-19 will provide a more comprehensive understanding of the clinical, epidemiological, and radiologic characteristics of patients with COVID-19.
Asunto(s)
COVID-19/diagnóstico por imagen , Radiografía Torácica/métodos , SARS-CoV-2 , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/terapia , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Group B streptococcus (GBS) causes serious diseases in newborn infants, often resulting in lifelong neurologic impairments or death. Prophylactic vaccination of pregnant women prior to delivery could provide comprehensive protection, as early onset and late-onset disease and maternal complications potentially could be addressed. METHODS: Capsular polysaccharide conjugate vaccine GBS6 was designed using surveillance data yielded by whole-genome sequencing of a global collection of recently recovered GBS isolates responsible for invasive neonatal GBS disease. Capsular polysaccharides were isolated, oxidized using sodium periodate, and conjugated to CRM197 by reductive amination in dimethyl sulfoxide. Immune responses in mice and rhesus macaques were measured in a multiplex Luminex immunoglobulin G (IgG) assay and opsonophagocytic activity assays. RESULTS: The optimized conjugates were immunogenic, alone and in combination, in mice and rhesus macaques, inducing IgG antibodies that mediated opsonophagocytic killing. Active immunization of murine dams with GBS6 prior to mating resulted in serotype-specific protection of pups from a lethal challenge with GBS. Protection following passive administration of serotype-specific IgG monoclonal antibodies to dams demonstrated conclusively that anticapsular polysaccharide IgG alone is sufficient for protection. CONCLUSIONS: The findings support the ongoing clinical evaluation of maternal GBS6 vaccination as a potential alternative method to prevent GBS disease in infants.
Asunto(s)
Animales Recién Nacidos/inmunología , Inmunidad Materno-Adquirida/inmunología , Polisacáridos Bacterianos/inmunología , Infecciones Estreptocócicas/inmunología , Vacunas Estreptocócicas/inmunología , Streptococcus/inmunología , Vacunas Conjugadas/inmunología , Animales , Animales Recién Nacidos/microbiología , Anticuerpos Antibacterianos/inmunología , Femenino , Inmunización/métodos , Inmunoglobulina G/inmunología , Macaca mulatta/inmunología , Macaca mulatta/microbiología , Ratones , Serogrupo , Infecciones Estreptocócicas/microbiología , Vacunación/métodosRESUMEN
Emissivity-tunable metamaterials of layered refractory metal and dielectric have great potentials as a simple thermophotovoltaic (TPV) selective emitter due to its near-omnidirectional, polarization-independent, and broadband selective emissivity. However, it is known that the stability of the layered structure is limited by the oxidation of metals. While there still exists ambiguity concerning the main source of oxygen between adjacent oxide layers and external residual oxygen, most reports focus on the adjacent layers. In this report, thermal stability of a tungsten-based layered metamaterial is investigated under a high-vacuum environment with great care to reduce residual oxygen. The results show unprecedented thermal stability up to 1200 °C for 3 h without any measurable oxidation of metal. This implies that the interlayer diffusion of oxygen from adjacent oxide layers is not exclusively responsible for the oxidation of metal. At such a high temperature, the layered metamaterial theoretically yields a high convertible radiative power density of 3.04 W/cm2 with comparable spectral efficiency of 40.2%. Finally, after performing series of thermal tests under higher thermal loads, we propose a novel high-temperature degradation model for layered metamaterials, the stability of which is ultimately limited by the agglomeration of thin metal layers.
RESUMEN
BACKGROUND: Thermosoftening of the endotracheal tube (ETT) and telescoping the ETT into a rubber catheter have been suggested as a method for reducing epistaxis during nasotracheal intubation (NTI). However, thermosoftening technique is known to make it difficult to navigate the ETT into trachea without the use of Magill forceps during NTI. The cuff inflation technique has been suggested as an effective alternative to the use of Magill forceps to improve the oropharyngeal navigation of the ETT, irrespective of their stiffness, during direct laryngoscope-guided NTI. We evaluated whether thermosoftening of the ETT telescoped into rubber catheters has an additional benefit in reducing nasal injury. Simultaneously, we also evaluated whether thermosoftening of the ETT worsened orotracheal navigability during cuff inflation-supplemented videolaryngoscope-guided NTI. METHODS: One hundred forty patients were randomly assigned to 1 of the 2 groups depending on whether the ETT was softened by warming or not. The primary outcome was the incidence of epistaxis during NTI. The secondary outcome was nasotracheal navigability of the ETT, assessed by navigation grade and time required for insertion of ETT in each phase (from nose to oropharynx, from oropharynx to glottic inlet aided by cuff inflation if needed, and from glottic inlet to trachea). RESULTS: The ETTs were successfully inserted through the selected nostril of all 140 patients. In the thermosoftening group, the incidence and severity of epistaxis was significantly lower (7% vs 51%; difference of 44.2%; 95% confidence interval, 29.9%-56.2%; P < .001), and the ETT passed through the nasal cavity with lower resistance (P = .001) and less time (P < .001) when compared to the control group. No difference was found in the ease of ETT insertion (navigation grade and time required) from the oropharynx to the glottic inlet (P > .99 and P = .054, respectively) and from the glottic inlet to the trachea (P > .99 and P = .750, respectively) between the 2 groups. In both groups, all ETTs could be navigated into the trachea without the use of Magill forceps. CONCLUSIONS: Supplemented with cuff inflation during videolaryngoscope-guided NTI, thermosoftening of the ETT telescoped into rubber catheters has a substantial benefit because it significantly reduces the incidence of epistaxis without worsening the oropharyngeal navigability of the ETT.
Asunto(s)
Catéteres , Calor/uso terapéutico , Intubación Intratraqueal/métodos , Laringoscopía/métodos , Cirugía Asistida por Video/métodos , Adulto , Método Doble Ciego , Femenino , Humanos , Intubación Intratraqueal/instrumentación , Laringoscopía/instrumentación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Cirugía Asistida por Video/instrumentaciónRESUMEN
BACKGROUND: Dizziness is one of the most common complaints in medicine and a frequent symptom among older people. Dizziness has a considerable impact on life quality and is associated with high economic costs. The purpose of this study was to evaluate the prevalence of dizziness in the general population and to describe its clinical characteristics and associated factors. METHODS: The Korea National Health and Nutrition Examination Survey (KNHANES) is a cross-sectional survey of the civilian, non-institutionalized population of South Korea. We evaluated data for 12,653 participants (5,450 men and 7,203 women), aged 40 years and above, whom participated in the KNHANES between 2010 and 2012. RESULTS: In the age group over 40 years old, the 1-year prevalence of dizziness was 20.10%. Dizziness was more prevalent among women (25.18%) than among men (14.57%; P < 0.001) and the prevalence rate increased with age (P < 0.001). In multivariable analysis, female sex, older age, serum triglyceride level, experience of depression, limited functional status owing to visual acuity impairment, limited physical performance, smoking, alcohol consumption, and perception of stress were independently associated with dizziness. CONCLUSIONS: In our study, the prevalence of dizziness in the general population was 20.10%. There was a stronger relationship between dizziness and physical performance, chronic diseases, and health behaviors compared to that with otologic diseases. Interventions for dizziness should be approached in a multifactorial manner and an understanding of various factors is necessary for the prevention and management of this condition.
Asunto(s)
Mareo/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , República de Corea/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Recently, the American Joint Committee on Cancer published the 8th edition of its Cancer Staging Manual with major changes regarding the staging of thyroid cancer, including the raising of the age cutoff from 45 to 55 years. Using the clinical and genetic data of 505 papillary thyroid cancer (PTC) cases, we aimed to compare overall survival (OS) and recurrence-free survival (RFS) with different age cutoff values, and also investigate the efficacy of the new staging system on a genomic level. METHODS: We downloaded gene expression data, somatic mutation profile, copy number alteration data and clinical data of 505 PTC patients from The Cancer Genome Atlas data portal. We used multiple statistical analysis and multiplatform genomic analysis to evaluate the efficacy of the 8th edition. RESULTS: When using 55 years as the cutoff value for analyzing RFS, the Kaplan-Meier plot showed a significant p value but not when using 45 years (p = 0.006 vs. p = 0.493), but both cutoff values were significant when analyzing OS (p = 1.1 × 10-9 with age 55 vs. p = 4.4 × 10-5 with age 45). When looking at stage-dependent survival, both the 7th and 8th edition had significant p values (p = 0.048 vs. p = 3.1 × 10-9 in RFS and p = 5.9 × 10-10 vs. p = 2.2 × 10-10 in OS). Multiplatform genomic analysis showed patients ≥55 years had 103 differently expressed genes when compared with other age groups. Signaling pathway analysis revealed that patients ≥55 years had altered pathways associated with aggressiveness of thyroid cancer. CONCLUSION: In conclusion, this is the first study to show clinical and genetic evidence supporting the altered age cutoff point of 55 years in the AJCC 8th edition for PTC patients.
Asunto(s)
Estadificación de Neoplasias , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Variaciones en el Número de Copia de ADN , Supervivencia sin Enfermedad , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Transducción de Señal , Cáncer Papilar Tiroideo/mortalidad , Neoplasias de la Tiroides/mortalidadRESUMEN
BACKGROUND: Sedentary behavior is considered an independent cause of cardio-metabolic diseases, regardless of physical activity level and obesity. Few studies have reported the association between leisure sedentary time and cardio-vascular diseases in terms of occupation. METHODS: We performed a cross-sectional study using data from the Korean Community Health Survey (KCHS) for 240,086 participants assessed in 2011 and 2013. Occupation was categorized into four groups: farmer or fisherman, laborer, and soldier (Group I); service worker, salesperson, technician, mechanic, production worker, and engineer (Group II); manager, expert, specialist, and clerk (Group III); and unemployed (Group IV). Leisure sedentary time was divided into five groups: 0 h, 1 h, 2 h, 3 h, and 4+ h. The association between leisure sedentary time on weekdays and hypertension/diabetes mellitus/hyperlipidemia for different occupations was analyzed using simple and multiple logistic regression analyses with complex sampling. RESULTS: In Groups I, II and III, no length of sedentary time was associated with hypertension, and only 3 h or 4+ h of sedentary time was associated with diabetes mellitus and hyperlipidemia. Group IV showed a significant association with hypertension and diabetes mellitus for the 2 h, 3 h, and 4+ h sedentary times. CONCLUSIONS: The unemployed are more susceptible than other occupation groups to cardio-metabolic diseases when leisure time is sedentary.
Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Hiperlipidemias/epidemiología , Hipertensión/epidemiología , Actividades Recreativas , Conducta Sedentaria , Adulto , Estudios Transversales , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Humanos , Hiperlipidemias/fisiopatología , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Ocupaciones/clasificación , República de Corea/epidemiología , Encuestas y CuestionariosRESUMEN
BACKGROUND: This study aims to determine the relationship between expression levels of ALDH2 and SOD2 genes and clinical parameters such as alcohol drinking, tobacco smoking, primary site of HNSCC, and human papilloma virus (HPV) state. METHODS: Gene expression data were obtained from gene expression omnibus (GEO accession number: GSE65858). Clinical data (N = 270) including survival result, gender, age, TNM stage, primary site of HNSCC, HPV status, alcohol drinking, and tobacco smoking habit were analyzed according to gene expression pattern. RESULTS: ALDH2 gene was expressed in low levels in patients with heavy alcohol consumption. It was expressed in high (p = 0.01) levels in patients with no or light alcohol consumption. ALDH2 gene was also expressed in low levels in patients with oral cavity cancers or hypopharynx cancers. However, ALDH2 gene was expressed in high (p = 0.03) levels in patients with oropharyngeal cancers or laryngeal cancers. HPV-positive patients were found to have high (p = 0.02) expression levels of ALDH2. SOD2 gene was expressed in high (p = 0.005) levels in patients who had greater mean pack-year of tobacco smoking. Based on log rank test, the group of patients with high expression of ALDH2 showed better (p = 0.002) clinical results than those with low expression of ALDH2. Difference of survival results between ALDH2 high-expressed group and ALDH2 low-expressed group was validated in another cohort (GSE39368, N = 138). CONCLUSIONS: Heavy alcohol drinking downregulates ALDH2 gene expression level. Heavy smoking up-regulates SOD2 gene expression level in patients with head and neck squamous cell carcinoma. The group of patients with low expression levels of ALDH2 showed significantly poorer survival results compared to those with high expression levels of ALDH2.
Asunto(s)
Consumo de Bebidas Alcohólicas/patología , Aldehído Deshidrogenasa Mitocondrial/metabolismo , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/patología , Superóxido Dismutasa/metabolismo , Fumar Tabaco/patología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/virología , Regulación hacia Abajo , Femenino , Perfilación de la Expresión Génica/métodos , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/virología , Humanos , Masculino , Análisis por Micromatrices/métodos , Persona de Mediana Edad , Papillomaviridae/aislamiento & purificación , Pronóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello , Análisis de Supervivencia , Regulación hacia ArribaRESUMEN
The ghost ant Tapinoma melanocephalum is a common household pest worldwide. The present study examined the occurrence of the species in urban homes in Korea. During the period of September 2014 to January 2016, T. melanocephalum workers were collected from 58 homes at 29 different localities using bait traps with 10% sugar solution. The species was widely distributed throughout urban homes at 29 different localities, and the indoor occurrence of T. melanocephalum was highest in Seoul (32.7%) and metropolitan areas of Gyeonggi-do (Province) (29.3%). The indoor incidence rate of T. melanocephalum peaked in September (22.8%), remained moderate from October through April, and peaked again in May (15.7%). In contrast, a low incidence was observed from June to August (7.0%). The present study provides evidence that native ants, such as T. melanocephalum, are potential indoor pests of homes in Korea throughout the year.
Asunto(s)
Vivienda/estadística & datos numéricos , Himenópteros , Animales , Humanos , Himenópteros/patogenicidad , Incidencia , Control de Plagas , República de Corea/epidemiología , Estaciones del Año , Seúl , UrbanizaciónRESUMEN
INTRODUCTION: We aimed to evaluate the association between specific anti-cyclic citrullinated peptide antibody (ACCPA) and pulmonary abnormalities in rheumatoid arthritis (RA) subjects. METHODS: Computed tomography (CT) images of 83 subjects with RA were evaluated in a blind fashion. Enrolled subjects underwent autoantibody testing to determinate titer of ACCPA and rheumatoid factor, and pulmonary function testing. Visual CT assessment included lobar analysis for extent of semi-quantitative total interstitial lung disease score (ILDS) and each airway abnormality score (bronchiectasis, bronchial wall thickening, centrilobular nodules, and expiratory air trapping). Correlation tests, and simple and multiple regression analyses were performed to determine the relationship between the visual CT abnormalities, physiologic parameters, and autoantibody titers. RESULTS: ACCPA-positive subjects had a greater extent and higher prevalence of small airway abnormalities including centrilobular nodules and air trapping compared to ACCPA-negative subjects (all p < 0.05). Bronchiectasis and bronchial wall thickening correlated with the ratio of forced expiratory volume in 1 s and forced vital capacity (FVC) (r = -0.236 and r = -0.329, all p < 0.05), and ILDS correlated with FVC and the diffusing capacity of the lung for carbon monoxide (r = -0.218 and r = -0.366, all p < 0.05). Bronchial wall thickening and air trapping correlated with ACCPA titers (r = 0.235 and r = 0.264, all p < 0.05). Air trapping and bronchial wall thickening were significantly associated with ACCPA titers. CONCLUSION: In ACCPA (+) RA, visual CT assessment of large and small airways beyond RA-ILD, which is attributable to RA-related autoimmunity, can provide valuable information regarding airway abnormalities, regardless of the patients' physiologic airflow limitations.