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1.
Cancer Med ; 13(12): e7407, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38899534

RESUMEN

OBJECTIVES: To investigate the added value of extracellular volume fraction (ECV) and arterial enhancement fraction (AEF) derived from enhanced CT to conventional image and clinical features for differentiating between pleomorphic adenoma (PA) and atypical parotid adenocarcinoma (PCA) pre-operation. METHODS: From January 2010 to October 2023, a total of 187 cases of parotid tumors were recruited, and divided into training cohort (102 PAs and 51 PCAs) and testing cohort (24 PAs and 10 atypical PCAs). Clinical and CT image features of tumor were assessed. Both enhanced CT-derived ECV and AEF were calculated. Univariate analysis identified variables with statistically significant differences between the two subgroups in the training cohort. Multivariate logistic regression analysis with the forward variable selection method was used to build four models (clinical model, clinical model+ECV, clinical model+AEF, and combined model). Diagnostic performances were evaluated using receiver operating characteristic (ROC) curve analyses. Delong's test compared model differences, and calibration curve and decision curve analysis (DCA) assessed calibration and clinical application. RESULTS: Age and boundary were chosen to build clinical model, and to construct its ROC curve. Amalgamating the clinical model, ECV, and AEF to establish a combined model demonstrated superior diagnostic effectiveness compared to the clinical model in both the training and test cohorts (AUC = 0.888, 0.867). There was a significant statistical difference between the combined model and the clinical model in the training cohort (p = 0.0145). CONCLUSIONS: ECV and AEF are helpful in differentiating PA and atypical PCA, and integrating clinical and CT image features can further improve the diagnostic performance.


Asunto(s)
Adenoma Pleomórfico , Medios de Contraste , Neoplasias de la Parótida , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Adenoma Pleomórfico/diagnóstico por imagen , Adenoma Pleomórfico/patología , Persona de Mediana Edad , Neoplasias de la Parótida/diagnóstico por imagen , Neoplasias de la Parótida/patología , Tomografía Computarizada por Rayos X/métodos , Diagnóstico Diferencial , Anciano , Adulto , Curva ROC , Estudios Retrospectivos , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología
3.
Immune Netw ; 24(2): e7, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38725670

RESUMEN

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virus-infected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105 PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

4.
Am J Otolaryngol ; 45(4): 104356, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38703611

RESUMEN

PURPOSE: This study compared treatment and outcomes for patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) based on their travel distance to treatment facility. MATERIALS AND METHODS: Patients with cT1-4, N0-3, M0 HPV-positive OPSCC in the National Cancer Database from 2010 to 2019 were identified and split into four quartiles based on distance to facility, with quartile 4 representing patients with furthest travel distances. Multivariable-adjusted logistic regression and Cox proportional hazards modeling were used to analyze the primary outcome of treatment received, and secondary outcomes of clinical stage, overall survival, surgical approach (i.e., TORS versus other), and 30-day surgical readmissions. RESULTS: 17,207 patients with HPV-positive OPSCC were evenly distributed into four quartiles. Compared to patients in quartile 1, patients in quartile 4 were 40 % less likely to receive radiation versus surgery (OR = 0.60; 95 % CI = 0.54-0.66). Among the patients who received surgery, quartile 4 had a higher odds of receiving TORS treatment compared to quartile 1 (4v1: OR = 2.38; 95 % CI = 2.05-2.77), quartile 2 (4v2: OR = 2.31, 95 % CI = 2.00-2.66), and quartile 3 (4v3: OR = 1.75; 95 % CI = 1.54-1.99). Quartile 4 had a decreased odds of mortality compared to Quartile 1 (4v1: OR = 0.87; 95 % CI = 0.79-0.97). There were no differences among the quartiles in presenting stage and 30-day readmissions. CONCLUSIONS: This study found that patients with furthest travel distance to facility were more often treated surgically over non-surgical management, with TORS over open surgery, and had better overall survival. These findings highlight potential disparities in access to care for patients with HPV-positive OPSCC.


Asunto(s)
Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Masculino , Femenino , Neoplasias Orofaríngeas/mortalidad , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/virología , Persona de Mediana Edad , Anciano , Infecciones por Papillomavirus/terapia , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/mortalidad , Infecciones por Papillomavirus/virología , Resultado del Tratamiento , Accesibilidad a los Servicios de Salud , Estadificación de Neoplasias , Tasa de Supervivencia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/virología , Viaje , Factores de Tiempo
5.
J Chem Phys ; 160(20)2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38804489

RESUMEN

The thermophysical properties and elemental abundances of the noble gases in terrestrial materials can provide unique insights into the Earth's evolution and mantle dynamics. Here, we perform extensive ab initio molecular dynamics simulations to determine the melting temperature and sound velocity of neon up to 370 GPa and 7500 K to constrain its physical state and storage capacity, together with to reveal its implications for the deep interior of the Earth. It is found that solid neon can exist stably under the lower mantle and inner core conditions, and the abnormal melting of neon is not observed under the entire temperature (T) and pressure (P) region inside the Earth owing to its peculiar electronic structure, which is substantially distinct from other heavier noble gases. An inspection of the reduction for sound velocity along the Earth's geotherm evidences that neon can be used as a light element to account for the low-velocity anomaly and density deficit in the deep Earth. A comparison of the pair distribution functions and mean square displacements of MgSiO3-Ne and Fe-Ne alloys further reveals that MgSiO3 has a larger neon storage capacity than the liquid iron under the deep Earth condition, indicating that the lower mantle may be a natural deep noble gas storage reservoir. Our results provide valuable information for studying the fundamental behavior and phase transition of neon in a higher T-P regime, and further enhance our understanding for the interior structure and evolution processes inside the Earth.

6.
Food Chem Toxicol ; 188: 114636, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38582343

RESUMEN

Nonclinical studies involve in vitro, in silico, and in vivo experiments to assess the toxicokinetics, toxicology, and safety pharmacology of drugs according to regulatory requirements by a national or international authority. In this review, we summarize the potential effects of various underlying diseases governing the absorption, distribution, metabolism, and excretion (ADME) of drugs to consider the use of animal models of diseases in nonclinical trials. Obesity models showed alterations in hepatic metabolizing enzymes, transporters, and renal pathophysiology, which increase the risk of drug-induced toxicity. Diabetes models displayed changes in hepatic metabolizing enzymes, transporters, and glomerular filtration rates (GFR), leading to variability in drug responses and susceptibility to toxicity. Animal models of advanced age exhibited impairment of drug metabolism and kidney function, thereby reducing the drug-metabolizing capacity and clearance. Along with changes in hepatic metabolic enzymes, animal models of metabolic syndrome-related hypertension showed renal dysfunction, resulting in a reduced GFR and urinary excretion of drugs. Taken together, underlying diseases can induce dysfunction of organs involved in the ADME of drugs, ultimately affecting toxicity. Therefore, the use of animal models of representative underlying diseases in nonclinical toxicity studies can be considered to improve the predictability of drug side effects before clinical trials.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Animales , Humanos , Preparaciones Farmacéuticas/metabolismo , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Hígado/metabolismo , Hígado/efectos de los fármacos , Riñón/metabolismo , Riñón/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Tasa de Filtración Glomerular
8.
Adv Mater ; 36(26): e2309770, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38447017

RESUMEN

Percutaneous thermotherapy, a minimally invasive operational procedure, is employed in the ablation of deep tumor lesions by means of target-delivering heat. Conventional thermal ablation methods, such as radiofrequency or microwave ablation, to a certain extent, are subjected to extended ablation time as well as biosafety risks of unwanted overheating. Given its effectiveness and safety, percutaneous thermotherapy gains a fresh perspective, thanks to magnetic hyperthermia. In this respect, an injectable- and magnetic-hydrogel-construct-based thermal ablation agent is likely to be a candidate for the aforementioned clinical translation. Adopting a simple and environment-friendly strategy, a magnetic colloidal hydrogel injection is introduced by a binary system comprising super-paramagnetic Fe3O4 nanoparticles and gelatin nanoparticles. The colloidal hydrogel constructs, unlike conventional bulk hydrogel, can be easily extruded through a percutaneous needle and then self-heal in a reversible manner owing to the unique electrostatic cross-linking. The introduction of magnetic building blocks is exhibited with a rapid magnetothermal response to an alternating magnetic field. Such hydrogel injection is capable of generating heat without limitation of deep penetration. The materials achieve outstanding therapeutic results in mouse and rabbit models. These findings constitute a new class of locoregional interventional thermal therapies with minimal collateral damages.


Asunto(s)
Carcinoma Hepatocelular , Coloides , Hidrogeles , Neoplasias Hepáticas , Animales , Conejos , Ratones , Hidrogeles/química , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Coloides/química , Gelatina/química , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapéutico , Hipertermia Inducida/métodos , Línea Celular Tumoral , Inyecciones , Nanopartículas Magnéticas de Óxido de Hierro/química
9.
Liver Int ; 44(6): 1351-1362, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38436551

RESUMEN

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.


Asunto(s)
Carcinoma Hepatocelular , Aprendizaje Profundo , Neoplasias Hepáticas , Imagen por Resonancia Magnética , Invasividad Neoplásica , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Microvasos/diagnóstico por imagen , Microvasos/patología , Supervivencia sin Enfermedad , Recurrencia Local de Neoplasia
10.
Artículo en Inglés | MEDLINE | ID: mdl-38310864

RESUMEN

INTRODUCTION: The multiple treatment options available to patients with thyroid nodules can generate uncertainty and confusion. Radiofrequency ablation (RFA) and ethanol ablation (EA) are two alternative modalities to manage thyroid nodules. As patients more frequently utilize online resources to guide their decision-making, the quality of such resources must be evaluated. The goal of this study was to assess the quality of online patient materials relating to RFA and EA compared to standard thyroidectomy. METHODS: The terms "thyroidectomy," "thyroid radiofrequency ablation," and "thyroid ethanol ablation" were searched on Google. Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), Simple Measure of Gobbledygook (SMOG), and Patient Education Materials Assessment Tool (PEMAT) understandability and actionability were calculated for each website. Statistical analysis was conducted on SPSS Statistics. Google trends were used to determine search interest for each term (May 2016 - May 2021). RESULTS: Of the 77 websites that met our inclusion criteria (30 thyroidectomy sites, 30 RFA sites, and 17 EA sites), the average FRE, FKGL, and SMOG scores of the RFA websites were significantly worse than those of the thyroidectomy websites (p < 0.05). The FKGL and SMOG scores of the EA websites were significantly worse than those of the thyroidectomy websites (p < 0.05). The average understandability and actionability scores for thyroidectomy websites were significantly higher than those of RFA and EA websites (p < 0.05). CONCLUSION: Ablation websites have lower search interest, readability, validity, understandability, and actionability scores in comparison to traditional thyroidectomy websites. Our findings emphasize the need to consider readability and PEMAT scores when developing online educational resources for ablative alternatives to thyroidectomy to allow for greater patient accessibility.


Asunto(s)
Etanol , Internet , Ablación por Radiofrecuencia , Nódulo Tiroideo , Tiroidectomía , Humanos , Ablación por Radiofrecuencia/métodos , Etanol/uso terapéutico , Tiroidectomía/métodos , Nódulo Tiroideo/cirugía , Educación del Paciente como Asunto/métodos
11.
Laryngoscope ; 134(6): 2689-2696, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38217447

RESUMEN

OBJECTIVE(S): Despite advancements in imaging techniques and cytological analysis, plunging ranula remains a challenging surgical, radiologic, and pathologic phenomenon. Of the 18 patients we evaluated at our institution, we highlight three cases that illustrate the high rate of misleading imaging and cytological results when assessing plunging ranula. METHODS: Imaging results, biopsy findings, operative techniques, and pathological reports were reviewed from patients who had either a preoperative or postoperative diagnosis of ranula and underwent surgery by a single head and neck surgeon at a tertiary care center. RESULTS: Of the 18 identified patients, computed tomography was correct on preoperative imaging 73% of the time and magnetic resonance imaging was correct on preoperative imaging 71% of the time. Two patients underwent preoperative ultrasound and their ultrasound reports did not accurately diagnose the presence of a ranula. Two patients underwent preoperative fine needle aspiration biopsy due to inconclusive preoperative imaging, in which results suggested either a ranula or epidermal cyst. Both ultimately did not match the final pathology. Three of eighteen patients (17%) underwent an inappropriate initial surgery due to incorrect imaging diagnoses and/or biopsy findings. CONCLUSION: Despite use of preoperative modalities to distinguish plunging ranula from other cystic floor of mouth lesions, surgeons must be aware that no workup modality is fully precise. The potential for revision surgery must be included in all preoperative discussions for presumed plunging ranula. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2689-2696, 2024.


Asunto(s)
Ránula , Tomografía Computarizada por Rayos X , Humanos , Ránula/diagnóstico , Ránula/cirugía , Ránula/patología , Ránula/diagnóstico por imagen , Masculino , Femenino , Adulto , Imagen por Resonancia Magnética , Persona de Mediana Edad , Diagnóstico Diferencial , Biopsia con Aguja Fina , Ultrasonografía , Estudios Retrospectivos , Adolescente , Adulto Joven , Errores Diagnósticos
12.
Int J Mol Sci ; 25(2)2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38256178

RESUMEN

Unintended genetic modifications that occur during the differentiation and proliferation of human induced pluripotent stem cells (hiPSCs) can lead to tumorigenicity. This is a crucial concern in the development of stem cell-based therapies to ensure the safety and efficacy of the final product. Moreover, conventional genetic stability testing methods are limited by low sensitivity, which is an issue that remains unsolved. In this study, we assessed the genetic stability of hiPSCs and hiPSC-derived cardiomyocytes using various testing methods, including karyotyping, CytoScanHD chip analysis, whole-exome sequencing, and targeted sequencing. Two specific genetic mutations in KMT2C and BCOR were selected from the 17 gene variants identified by whole-exome and targeted sequencing methods, which were validated using droplet digital PCR. The applicability of this approach to stem cell-based therapeutic products was further demonstrated with associated validation according to the International Council for Harmonisation (ICH) guidelines, including specificity, precision, robustness, and limit of detection. Our droplet digital PCR results showed high sensitivity and accuracy for quantitatively detecting gene mutations, whereas conventional qPCR could not avoid false positives. In conclusion, droplet digital PCR is a highly sensitive and precise method for assessing the expression of mutations with tumorigenic potential for the development of stem cell-based therapeutics.


Asunto(s)
Células Madre Pluripotentes Inducidas , Humanos , Miocitos Cardíacos , Carcinogénesis , Diferenciación Celular/genética , Reacción en Cadena de la Polimerasa
13.
Laryngoscope ; 134(7): 3003-3011, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38251796

RESUMEN

OBJECTIVE: The primary objective of this study was to evaluate oncologic outcomes of all published cases of supracricoid partial laryngectomy (SCPL) performed in the United States. The secondary objective was to assess the functional outcomes associated with this procedure. REVIEW METHODS: A systematic review of PubMed, SCOPUS, and Embase for all English-language studies pertaining to SCPL performed in the United States was conducted until August 2021. Primary outcomes included disease-specific survival (DSS), overall survival, and local recurrence rate. Secondary outcomes included larynx preservation rate, gastrostromy tube dependency, days to gastrostomy tube removal, decannulation rate, and days to decannulation. RESULTS: A total of six studies were included in the analysis. A total of 113 patients (58.5%) underwent SCPL surgery as a primary treatment method whereas 80 patients (41.5%) underwent SCPL as salvage surgery. The 5-year DSS rates were 87.8% and 100% for primary and salvage procedures, respectively. Approximately 10.3% of patients undergoing a salvage SCPL procedure experienced a local recurrence whereas only 1.85% of primary SCPL procedures resulted in local recurrence. The rates of decannulation following primary and salvage SCPL were 92.7% and 88.1%, respectively. With regard to swallowing, primary and salvage SCPL procedures demonstrated comparably low postoperative gastrostomy tube dependency rates of 3.66% and 4.76%, respectively. CONCLUSIONS: SCPL performed in the United States is an effective surgical technique that produces excellent outcomes in qualifying patients, thus validating its viability as an organ-preserving surgical alternative. Laryngoscope, 134:3003-3011, 2024.


Asunto(s)
Cartílago Cricoides , Neoplasias Laríngeas , Laringectomía , Humanos , Laringectomía/métodos , Neoplasias Laríngeas/cirugía , Neoplasias Laríngeas/mortalidad , Estados Unidos/epidemiología , Cartílago Cricoides/cirugía , Resultado del Tratamiento , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/cirugía , Terapia Recuperativa/métodos , Terapia Recuperativa/estadística & datos numéricos
14.
Laryngoscope ; 134(2): 725-731, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37466312

RESUMEN

OBJECTIVE: Opportunities exist to improve intraoperative communication and documentation of resection margin details. We instituted a "frozen section timeout" that centers around visualization of the paired resection specimen and surgical defect-facilitating effective, bidirectional exchange of information. METHODS: We designed an interactive form for use during the "frozen section timeout" including annotated 3D virtual models of the resected specimen and surgical defect, plus a "line-item" table for primary and supplemental margin results. The "timeout" was conducted over a Zoom call between the operating room and frozen section laboratory. The form was simultaneously projected and discussed while all members of the surgical care team stopped activities. Nurses, co-surgeons, and all other members of the surgical team were encouraged to take part in this process. RESULTS: Twenty-six frozen section timeouts were conducted during head and neck surgeries in the Department of Otolaryngology at Mount Sinai West Hospital. These timeouts were facilitated by the lead surgeon, and all other activities were halted to ensure that critical information was shared, documented, and agreed upon. During the timeout, the annotated specimen and defect scans were displayed, clearly demonstrating the at-risk margins and the corresponding location and breadth of supplemental margins harvested. CONCLUSION: Incorporating a frozen section timeout can improve intraoperative communication, increase transparency, and potentially eliminate uncertainty regarding margin status and tumor clearance. Visualization of at-risk margins and the corresponding location and breadth of supplemental margins promises an unprecedented level of documentation and understanding. This novel technique can establish a new and improved standard of care. LEVEL OF EVIDENCE: NA Laryngoscope, 134:725-731, 2024.


Asunto(s)
Carcinoma de Células Escamosas , Secciones por Congelación , Humanos , Proyectos Piloto , Carcinoma de Células Escamosas/patología , Cuidados Intraoperatorios/métodos , Márgenes de Escisión , Estudios Retrospectivos
15.
Psychol Med ; 54(2): 359-373, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37376848

RESUMEN

BACKGROUND: Childhood is a crucial neurodevelopmental period. We investigated whether childhood reading for pleasure (RfP) was related to young adolescent assessments of cognition, mental health, and brain structure. METHODS: We conducted a cross-sectional and longitudinal study in a large-scale US national cohort (10 000 + young adolescents), using the well-established linear mixed model and structural equation methods for twin study, longitudinal and mediation analyses. A 2-sample Mendelian randomization (MR) analysis for potential causal inference was also performed. Important factors including socio-economic status were controlled. RESULTS: Early-initiated long-standing childhood RfP (early RfP) was highly positively correlated with performance on cognitive tests and significantly negatively correlated with mental health problem scores of young adolescents. These participants with higher early RfP scores exhibited moderately larger total brain cortical areas and volumes, with increased regions including the temporal, frontal, insula, supramarginal; left angular, para-hippocampal; right middle-occipital, anterior-cingulate, orbital areas; and subcortical ventral-diencephalon and thalamus. These brain structures were significantly related to their cognitive and mental health scores, and displayed significant mediation effects. Early RfP was longitudinally associated with higher crystallized cognition and lower attention symptoms at follow-up. Approximately 12 h/week of youth regular RfP was cognitively optimal. We further observed a moderately significant heritability of early RfP, with considerable contribution from environments. MR analysis revealed beneficial causal associations of early RfP with adult cognitive performance and left superior temporal structure. CONCLUSIONS: These findings, for the first time, revealed the important relationships of early RfP with subsequent brain and cognitive development and mental well-being.


Asunto(s)
Salud Mental , Placer , Adulto , Adolescente , Humanos , Niño , Estudios Longitudinales , Estudios Transversales , Lectura , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Cognición
16.
EBioMedicine ; 99: 104932, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38118400

RESUMEN

BACKGROUND: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to approximately 500 million cases and 6 million deaths worldwide. Previous investigations into the pathophysiology of SARS-CoV-2 primarily focused on peripheral blood mononuclear cells from patients, lacking detailed mechanistic insights into the virus's impact on inflamed tissue. Existing animal models, such as hamster and ferret, do not faithfully replicate the severe SARS-CoV-2 infection seen in patients, underscoring the need for more relevant animal system-based research. METHODS: In this study, we employed single-cell RNA sequencing (scRNA-seq) with lung tissues from K18-hACE2 transgenic (TG) mice during SARS-CoV-2 infection. This approach allowed for a comprehensive examination of the molecular and cellular responses to the virus in lung tissue. FINDINGS: Upon SARS-CoV-2 infection, K18-hACE2 TG mice exhibited severe lung pathologies, including acute pneumonia, alveolar collapse, and immune cell infiltration. Through scRNA-seq, we identified 36 different types of cells dynamically orchestrating SARS-CoV-2-induced pathologies. Notably, SPP1+ macrophages in the myeloid compartment emerged as key drivers of severe lung inflammation and fibrosis in K18-hACE2 TG mice. Dynamic receptor-ligand interactions, involving various cell types such as immunological and bronchial cells, defined an enhanced TGFß signaling pathway linked to delayed tissue regeneration, severe lung injury, and fibrotic processes. INTERPRETATION: Our study provides a comprehensive understanding of SARS-CoV-2 pathogenesis in lung tissue, surpassing previous limitations in investigating inflamed tissues. The identified SPP1+ macrophages and the dysregulated TGFß signaling pathway offer potential targets for therapeutic intervention. Insights from this research may contribute to the development of innovative diagnostics and therapies for COVID-19. FUNDING: This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020M3A9I2109027, 2021R1A2C2004501).


Asunto(s)
COVID-19 , Melfalán , gammaglobulinas , Animales , Cricetinae , Ratones , Humanos , SARS-CoV-2 , Leucocitos Mononucleares , Hurones , Bronquios , Factor de Crecimiento Transformador beta , Ratones Transgénicos , Modelos Animales de Enfermedad , Pulmón
17.
Virol J ; 20(1): 285, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38041113

RESUMEN

BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has challenged the effectiveness of current therapeutic regimens. Here, we aimed to develop a potent SARS-CoV-2 antibody with broad neutralizing effect by screening a scFv library with the spike protein receptor-binding domain (RBD) via phage display. METHODS: SKAI-DS84 was identified through phage display, and we performed pseudovirus neutralization assays, authentic virus neutralization assays, and in vivo neutralization efficacy evaluations. Furthermore, surface plasmon resonance (SPR) analysis was conducted to assess the physical characteristics of the antibody, including binding kinetics and measure its affinity for variant RBDs. RESULTS: The selected clones were converted to human IgG, and among them, SKAI-DS84 was selected for further analyses based on its binding affinity with the variant RBDs. Using pseudoviruses, we confirmed that SKAI-DS84 was strongly neutralizing against wild-type, B.1.617.2, B.1.1.529, and subvariants of SARS-CoV-2. We also tested the neutralizing effect of SKAI-DS84 on authentic viruses, in vivo and observed a reduction in viral replication and improved lung pathology. We performed binding and epitope mapping experiments to understand the mechanisms underlying neutralization and identified quaternary epitopes formed by the interaction between RBDs as the target of SKAI-DS84. CONCLUSIONS: We identified, produced, and tested the neutralizing effect of SKAI-DS84 antibody. Our results highlight that SKAI-DS84 could be a potential neutralizing antibody against SARS-CoV-2 and its variants.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Anticuerpos Monoclonales , Pruebas de Neutralización , Receptores Virales/metabolismo , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Glicoproteína de la Espiga del Coronavirus/química
18.
Gland Surg ; 12(11): 1500-1507, 2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38107486

RESUMEN

Background: Despite the high incidence of lateral neck lymph node (LN) metastasis in papillary thyroid cancer (PTC), the management of the lateral neck remains controversial. We aimed to map the draining LNs in the lateral neck using carbon nanoparticles and explore its potential in neck evaluation. Methods: We conducted a multicenter, prospective study in PTC patients who had non-palpable yet suspicious metastatic lateral LNs on ultrasound and/or computed tomography (CT) but could not be confirmed by fine needle aspiration. Carbon nanoparticle suspension was injected peritumorally into the thyroid and modified lateral neck dissection was subsequently performed. Results: A total of 154 patients were enrolled for analysis. And 5,070 lateral LNs were removed, of which 1,079 (21.3%) were dyed. The median of dyed LNs was 6 per case (range, 1-33). The distribution of dyed LNs in neck compartments was IV > III > IIA > IIB/V, independent of tumor size, location, multifocality or microscopic extra-thyroidal extension (ETE). Compared with undyed LNs, the probabilities of metastasis in dyed LNs were significantly increased in compartment III, IV, V, and II-V (III: 29.3% vs. 15.4%, P<0.001; IV: 26.3% vs. 14.5%, P<0.001; V: 16.7% vs. 3.3%, P=0.005; II-V: 26.3% vs. 10.0%, P<0.001). The relative risks of metastasis in dyed LNs compared with undyed LNs were 1.90, 1.82, 5.04 and 2.62 in compartment III, IV, V, and II-V, respectively. Conclusions: It was the first prospective multicenter study to map the lateral neck LNs with carbon nanoparticles, which could help surgeons visualize the suspicious LNs during surgery. Instead of unguided LN biopsy, this method has a potential role in lateral neck assessment for indeterminate lateral LNs in PTC.

20.
Laryngoscope ; 2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37921378

RESUMEN

We present a novel, efficient approach to demonstrating supplemental margins during oncologic resection. Surgeons and pathologists annotated 10 virtual models of surgical defects and resection specimens in 3D using an iPad-based application, Procreate®. Incorporating this method into the surgical workflow can improve interdepartmental communication and provide visual documentation of surgical steps taken to address at-risk margins. Laryngoscope, 2023.

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