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BACKGROUND: Currently, diverse minipigs have acquired a common dwarfism phenotype through independent artificial selections. Characterizing the population and genetic diversity in minipigs is important to unveil genetic mechanisms regulating their body sizes and effects of independent artificial selections on those genetic mechanisms. However, full understanding for the genetic mechanisms and phenotypic consequences in minipigs still lag behind. RESULTS: Here, using whole genome sequencing data of 41 pig breeds, including eight minipigs, we identified a large genomic diversity in a minipig population compared to other pig populations in terms of population structure, demographic signatures, and selective signatures. Selective signatures reveal diverse biological mechanisms related to body size in minipigs. We also found evidence for neural development mechanism as a minipig-specific body size regulator. Interestingly, selection signatures within those mechanisms containing neural development are also highly different among minipig breeds. Despite those large genetic variances, PLAG1, CHM, and ESR1 are candidate key genes regulating body size which experience different differentiation directions in different pig populations. CONCLUSIONS: These findings present large variances of genetic structures, demographic signatures, and selective signatures in the minipig population. They also highlight how different artificial selections with large genomic diversity have shaped the convergent dwarfism.
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Nanismo , Porco Miniatura , Animais , Porco Miniatura/genética , Suínos , Nanismo/genética , Nanismo/veterinária , Tamanho Corporal/genética , Fenótipo , Seleção Genética , Variação Genética , Genômica , Sequenciamento Completo do GenomaRESUMO
Enhancing the mobility of lithium-ions (Li+) through surface engineering is one of major challenges facing fast-charging lithium-ion batteries (LIBs). In case of demanding charging conditions, the use of a conventional artificial graphite (AG) anode leads to an increase in operating temperature and the formation of lithium dendrites on the anode surface. In this study, a biphasic zeolitic imidazolate framework (ZIF)-AG anode, designed strategically and coated with a mesoporous material, is verified to improve the pathways of Li+ and electrons under a high charging current density. In particular, the graphite surface is treated with a coating of a ZIF-8-derived carbon nanoparticles, which addresses sufficient surface porosity, enabling this material to serve as an electrolyte reservoir and facilitate Li+ intercalation. Moreover, the augmentation in specific surface area proves advantageous in reducing the overpotential for interfacial charge transfer reactions. In practical terms, employing a full-cell with the biphasic ZIF-AG anode results in a shorter charging time and improved cycling performance, demonstrating no evidence of Li plating during 300 cycles under 3.0 C-charging and 1.0 C-discharging. The research endeavors to contribute to the progress of anode materials by enhancing their charging capability, aligning with the increasing requirements of the electric vehicle applications.
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PURPOSE: The clinical significance of negative toxin enzyme immunoassays (EIA) for Clostridioides difficile infections (CDIs) is unclear. Our study aimed to investigate the significance of toxin EIA-negative in the diagnosis and prognosis of CDI. METHODS: All stool specimens submitted for C. difficile toxin EIA testing were cultured to isolate C. difficile. In-house PCR for tcdA, tcdB, cdtA, and cdtB genes were performed using C. difficile isolates. Stool specimens were tested with C. difficile toxins A and B using EIA kit (RIDASCREEN Clostridium difficile toxin A/B, R-Biopharm AG, Darmstadt, Germany). Characteristics and subsequent CDI episodes of toxin EIA-negative and -positive patients were compared. RESULTS: Among 190 C. difficile PCR-positive patients, 83 (43.7%) were toxin EIA-negative. Multivariate analysis revealed independent associations toxin EIA-negative results and shorter hospital stays (OR = 0.98, 95% CI 0.96-0.99, p = 0.013) and less high-risk antibiotic exposure in the preceding month (OR = 0.38, 95% CI 0.16-0.94, p = 0.035). Toxin EIA-negative patients displayed a significantly lower white blood cell count rate (11.0 vs. 35.4%, p < 0.001). Among the 54 patients who were toxin EIA-negative and did not receive CDI treatment, three (5.6%) were diagnosed with CDI after 7-21 days without complication. CONCLUSION: Our study demonstrates that toxin EIA-negative patients had milder laboratory findings and no complications, despite not receiving treatment. Prolonged hospitalisation and exposure to high-risk antibiotics could potentially serve as markers for the development of toxin EIA-positive CDI.
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Proteínas de Bactérias , Toxinas Bacterianas , Clostridioides difficile , Infecções por Clostridium , Fezes , Humanos , Clostridioides difficile/genética , Fezes/microbiologia , Masculino , Feminino , Toxinas Bacterianas/análise , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/microbiologia , Idoso , Pessoa de Meia-Idade , Proteínas de Bactérias/genética , Proteínas de Bactérias/análise , Enterotoxinas/análise , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Técnicas Imunoenzimáticas , Adulto , Resultado do Tratamento , Reação em Cadeia da Polimerase , PrognósticoRESUMO
PURPOSE: Postoperative laryngeal edema (PLE) is a common complication in patients undergoing head and neck surgery, leading to symptoms such as odynophagia, dysphagia, or potential airway obstruction. However, the prevalence and risk factors of PLE in patients undergoing neck dissection (ND) have not been well investigated. METHODS: A retrospective analysis was conducted in three steps. Initially, a pilot study of 50 consecutive ND patients revealed a preliminary PLE prevalence of 0.34. Then, the medical records of an additional 295 ND patients were reviewed to estimate the prevalence of PLE with a total width of 95% confidence interval (CI) of ± 5%. Finally, multivariable logistic regression analyses were performed to identify risk factors for PLE (n = 343). RESULTS: PLE occurred in 29.4% [95%CI 24.4-34.4%] of patients undergoing any type of ND, with the most common symptoms of odynophagia (75.0%) and dyspnea (11.1%). Hospital stay was just one day longer in PLE patients, responding well with short-term steroid treatment (p = 0.0057). In multivariable analyses, no significant association was found between PLE occurrence and airway management. However, body mass index and the American Society of Anesthesiologists classification correlated with PLE. More importantly, surgery for oro-hypopharynx or supraglottis tumors (odds ratio, OR = 3.019, [95%CI 1.166-7.815]) and lymph node level 2(3) ND (OR = 4.214 to 5.279, [95%CI 1.160-20.529]) were significant risk factors for PLE. CONCLUSIONS: PLE developed in approximately 30% of ND patients, causing uncomfortable symptoms. Early diagnosis and intervention of PLE in high-risk patients can improve patient care and outcomes.
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Edema Laríngeo , Esvaziamento Cervical , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Esvaziamento Cervical/efeitos adversos , Fatores de Risco , Pessoa de Meia-Idade , Estudos Retrospectivos , Edema Laríngeo/epidemiologia , Edema Laríngeo/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prevalência , Idoso , Adulto , Projetos Piloto , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/epidemiologiaRESUMO
Medication-related osteonecrosis of the jaws (MRONJ) is a serious condition often linked with antiresorptive, immune modulating, and antiangiogenic drugs, initially associated with bisphosphonates but now including a broader range of medications. Tocilizumab, an interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody used for conditions like rheumatoid arthritis and recently for COVID-19 to reduce IL-6 activity and alleviate symptoms, has raised concerns over its potential to induce MRONJ, particularly in post-COVID-19 patients. A case involving a 36-year-old male who developed tooth mobility and pain in the right maxillary posterior region after COVID-19 treatment with tocilizumab and dexamethasone is highlighted. Despite treatments like antibiotics, the necrosis persisted until more extensive surgery was performed, leading to improvement without recurrence over 2 years. This case emphasizes the need for awareness and research into the risk of MRONJ in patients treated with tocilizumab after COVID-19, underlining the importance for healthcare professionals to recognize and manage this complication.
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Anticorpos Monoclonais Humanizados , Tratamento Farmacológico da COVID-19 , COVID-19 , Osteonecrose , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Adulto , COVID-19/complicações , Osteonecrose/induzido quimicamente , SARS-CoV-2 , Dexametasona/uso terapêutico , MaxilaRESUMO
OBJECTIVE: Narrowing of the palatal cleft is often observed in infants with Robin sequence (RS) treated with the Stanford Orthodontic Airway Plate treatment (SOAP) even though SOAP is utilized primarily to establish airway patency. The current study quantified dimensional changes of the cleft palate (CP) in infants with RS treated with SOAP. DESIGN: A retrospective chart review. PATIENTS: Infants with RS and CP who completed SOAP and had maxillary arch models at both pre- and post-treatment time points at a single tertiary referral hospital between September 2019 and July 2023. SETTING AND OUTCOME MEASURE: Maxillary arch models were measured and analyzed using Bivariate statistical analysis. RESULTS: Seventeen infants were included in the study. The median age (min, max) was 6.7 weeks (1.1, 21.9) at pre-treatment and 26.6 weeks (18.7, 37.0) at post-treatment. The median Obstructive Apnea Hypopnea Index was 36.2 events/hour (8.1, 103.1) at pre-treatment and 4.1 events/hour (1.9, 8.6) at post-treatment. The pre-treatment width of CP decreased by an average (± standard diviation) of 6.37 mm (± 3.55, p < 0.001) at post-treatment. The ratio of the posterior cleft width to the total maxillary arch width decreased from 40% (± 9.1) at pre-treatment to 22% (± 11) at post-treatment (p < 0.001). CONCLUSION: The dimensions of CP reduced significantly during SOAP in infants with RS and CP treated for their severe upper airway obstruction. The findings highlight a potential benefit of SOAP that may contribute favorably to the palate repair surgery.
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BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) can cause significant pain and loss of aesthetics and function if not treated properly. However, diagnosis still relies on detailed intraoral examinations and imaging. Prognosis varies even among patients with similar stages or conditions of MRONJ, emphasizing the need for a deeper understanding of its complex mechanisms. Thus, this study aimed to identify the oral microbiota of patients with MRONJ. METHODS: This single-center prospective cohort study included patients with confirmed MRONJ who visited the Department of Oral and Maxillofacial Surgery at Yonsei University Dental Hospital between 2021 and 2022. Oral swab samples were collected from the affected and unaffected sides of each patient. The composition and enumeration of the microbial communities were analyzed, and the diversity was compared to verify ecological changes in the groups using a next-generation sequencing-based 16S metagenomic analysis. A statistical analysis was performed using Wilcoxon signed-rank test with SPSS version 22, and values of P less than 0.05 were considered statistically significant. RESULTS: The final study sample included 12 patients. The mean age was 82.67 ± 5.73 (range, 72-90) years. Changes in microbial composition were observed at different taxonomic levels (phylum, genus, and species). The identified microorganisms were commonly associated with periodontitis, gingival disease, and endodontic infection, suggesting a multifactorial etiology of MRONJ. CONCLUSIONS: Although this study is based on a small number of cases, it shows that MRONJ is not caused by a specific microorganism but can rather be caused by a variety of factors. By addressing these findings in large-scale studies, the significance of oral microbiome in pathogenesis can be further elucidated and can facilitate the development of effective therapeutic interventions for patients with MRONJ.
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Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Microbiota , Periodontite , Humanos , Idoso , Idoso de 80 Anos ou mais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Estudos Prospectivos , Periodontite/complicações , DifosfonatosRESUMO
BACKGROUND: The emergence of carbapenem-resistant Enterobacterales (CRE) infections is rapidly increasing and represents a serious public threat. In 2020, a total of 16,883 carbapenemase-producing Enterobacterales strains were collected; among these isolates, 21 strains were repeatedly isolated in a local tertiary care hospital. METHODS: Antimicrobial susceptibility testing was performed using the broth microdilution method. All 21 strains of CRKP were analyzed by PFGE after XbaI digestion. The 21 CRKP strains were sequenced on the Illumina Miseq and Oxford Nanopore GridION platforms. RESULTS: These 21 CRKP isolates showed an identical antimicrobial resistance profile, including resistance to ampicillin, carbapenems, cephems, chloramphenicol, fluoroquinolone, macrolides and trimethoprim/sulfamethoxazole. Based on whole-genome analysis, these 21 CRKP isolates shared a common genetic structure (ISAba125-IS630-blaNDM-1-bleMBL) and harbored additional resistance determinants (blaOXA-1, blaCTX-M-15, blaSHV-11, blaSHV-67, aac(6')-Ib-cr, qnrS1, OqxA, OqxB, catB3, mph(A), sul1, and dfrA12) and mutations in the quinolone resistance-determining regions of gyrA (S83I) and parC (S80I). These isolates belonged to the ST147 and KL64 capsular types, which were carried on IncFIB replicon plasmids. The 21 CRKP strains collected from one hospital were divided into five PFGE patterns, and they were closely related with a minimum similarity value of 95.2%. These isolates were found to be highly related based on the presence of between 2 and 27 SNPs. CONCLUSIONS: These findings indicate that NDM-1-producing K. pneumoniae ST147 may have been introduced via a common source, implying nosocomial transmission; furthermore, continuous monitoring is necessary to prevent endemic transmission.
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Enterobacteriáceas Resistentes a Carbapenêmicos , Klebsiella pneumoniae , Humanos , Klebsiella pneumoniae/genética , Centros de Atenção Terciária , República da Coreia/epidemiologia , Antibacterianos/farmacologia , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Carbapenêmicos/farmacologiaRESUMO
OBJECTIVES: Reflectance confocal microscopy (RCM) is an imaging method that can noninvasively visualize microscopic features of the human skin. The utility of RCM can be further improved by increasing imaging speed. In this paper, we report high-speed RCM imaging of human skin with a frame rate that is over 10 times faster and an area imaging rate that is 6-9 times faster than those of commercially available RCM devices. METHODS: The higher imaging speed was achieved using a high-speed RCM technique, termed spectrally encoded confocal microscopy (SECM). SECM uses a diffraction grating and a high-speed, wavelength-swept source to conduct confocal imaging at a very high rate. We developed a handheld SECM probe using a scanned-grating approach. The SECM probe was used in conjunction with a wavelength-swept source with a spectral band of 1251-1342 nm. RESULTS: The SECM probe achieved high lateral resolution of 1.3-1.6 µm and an axial resolution of 3.5 µm. SECM images of the human skin (image size = 439 × 439 µm2 ) obtained at 100 frames/s clearly show previously reported RCM features of the human skin in vivo with adequate image quality. The fast imaging speed allowed for the rapid acquisiton of volumetric SECM image data (200 frames covering a depth range of 200 µm) within 2 s. The use of 1251-1342 nm provided sufficient signal level and contrast required to visualize key cellular morphologic features. CONCLUSIONS: These preliminary results demonstrate that high-speed SECM imaging of the human skin at 1251-1342 nm is feasible.
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Pele , Humanos , Microscopia Confocal/métodosRESUMO
Mandibular asymmetry has a variety of patterns because they are affected the position and the shape of mandible in addition to the overlying soft tissue. This study aimed to assess the factor in mandibular asymmetry, focusing on each mandibular functional units and the soft tissue thickness in the mandibular angle area. Forty patients who were diagnosed with facial asymmetry and undergone the orthognathic surgery without genioplasty were enrolled in this study. The skeletal patterns of the patients were analyzed by using cone-beam computed tomography data and 3D virtual images divided into 2 categories; the mandibular functional unit length and the soft tissue depth. All difference in bilateral mandibular functional unit lengths had a statistically significant with chin top deviation ( P <0.05). The greatest correlation was the condylar unit length compared with other functional units. The soft tissue thickness in the mandibular angle area was not statistically related to chin top deviation ( P >0.05), and the soft tissue did not change remarkably after orthognathic surgery ( P >0.05). This study suggests that the considerations of a surgical plan for treatment based on the mandibular asymmetry.
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Assimetria Facial , Mandíbula , Humanos , Assimetria Facial/diagnóstico por imagem , Assimetria Facial/cirurgia , Estudos Retrospectivos , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Queixo/cirurgia , Ossos Faciais , Imageamento Tridimensional/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Cefalometria/métodosRESUMO
Lip canting, which is a noticeable factor in patients with facial asymmetry, can be influenced by the dentofacial skeleton. During orthognathic surgery, postoperative changes in facial soft tissue occur along the newly positioned hard tissue. Therefore, the evaluation of soft tissue before surgery is important. The purpose of this study was to investigate the skeletal factors that can affect lip canting by statistically comparing 2 facial horizontal planes using a three-dimensional reconstruction model. The findings of the present study showed a statistical correlation between lip canting and 3 skeletal factors: menton deviation, maxillary canting, and ramal length differences. Furthermore, a statistical correlation was identified between the Frankfort Horizontal plane and the intercanthal plane compared with the lip canting line. This result suggests that the intercanthal plane could be a standard horizontal plane in three-dimensional reconstruction model analysis.
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Rheumatoid arthritis (RA) is an autoimmune disease of the joint synovial membranes. RA is difficult to prevent or treat; however, blocking proinflammatory cytokines is a general therapeutic strategy. Pulsed electromagnetic field (PEMF) is reported to alleviate RA's inflammatory response and is being studied as a non-invasive physical therapy. In this current study, PEMF decreased paw inflammation in a collagen-induced arthritis (CIA) murine model. PEMF treatment at 10 Hz was more effective in ameliorating arthritis than at 75 Hz. In the PEMF-treated CIA group, the gross inflammation score and cartilage destruction were lower than in the untreated CIA group. The CIA group treated with PEMF also showed lower serum levels of IL-1ß but not IL-6, IL-17, or TNF-α. Serum levels of total anti-type II collagen IgG and IgG subclasses (IgG1, IgG2a, and IgG2b) remained unchanged. In contrast, tissue protein levels of IL-1ß, IL-6, TNF-α, receptor activator of nuclear factor kappa-Β (RANK), RANK ligand (RANKL), IL-6 receptor (IL-6R), and TNF-α receptor1 (TNFR1) were all lower in the ankle joints of the PEMF-treated CIA group compared with the CIA group. The results of this study suggest that PEMF treatment can preserve joint morphology cartilage and delay the occurrence of CIA. PEMF has potential as an effective adjuvant therapy that can suppress the progression of RA.
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Artrite Experimental , Artrite Reumatoide , Camundongos , Animais , Artrite Experimental/tratamento farmacológico , Fator de Necrose Tumoral alfa/uso terapêutico , Modelos Animais de Doenças , Campos Eletromagnéticos , Citocinas , Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico , Imunoglobulina G/uso terapêuticoRESUMO
Waning vaccine-induced immunity, coupled with the emergence of SARS-CoV-2 variants, has inspired the widespread implementation of COVID-19 booster vaccinations. Here, we evaluated the potential of the GX-19N DNA vaccine as a heterologous booster to enhance the protective immune response to SARS-CoV-2 in mice primed with either an inactivated virus particle (VP) or an mRNA vaccine. We found that in the VP-primed condition, GX-19N enhanced the response of both vaccine-specific antibodies and cross-reactive T Cells to the SARS-CoV-2 variant of concern (VOC), compared to the homologous VP vaccine prime-boost. Under the mRNA-primed condition, GX-19N induced higher vaccine-induced T Cell responses but lower antibody responses than the homologous mRNA vaccine prime-boost. Furthermore, the heterologous GX-19N boost induced higher S-specific polyfunctional CD4+ and CD8+ T cell responses than the homologous VP or mRNA prime-boost vaccinations. Our results provide new insights into booster vaccination strategies for the management of novel COVID-19 variants.
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Vacinas contra COVID-19 , COVID-19 , Linfócitos T , Animais , Humanos , Camundongos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , DNA , RNA Mensageiro/genética , SARS-CoV-2 , Vacinação , Vacinas de Produtos Inativados , Interferon gama/imunologia , Interferon gama/metabolismo , Vacinas de mRNARESUMO
BACKGROUND: DNA methylation is an important epigenetic modification that is known to regulate gene expression. Whole-genome bisulfite sequencing (WGBS) is a powerful method for studying cytosine methylation in a whole genome. However, it is difficult to obtain methylation profiles using the WGBS raw reads and is necessary to be proficient in all types of bioinformatic tools for the study of DNA methylation. In addition, recent end-to-end pipelines for DNA methylation analyses are not sufficient for addressing those difficulties. RESULTS: Here we present msPIPE, a pipeline for DNA methylation analyses with WGBS data seamlessly connecting all the required tasks ranging from data pre-processing to multiple downstream DNA methylation analyses. The msPIPE can generate various methylation profiles to analyze methylation patterns in the given sample, including statistical summaries and methylation levels. Also, the methylation levels in the functional regions of a genome are computed with proper annotation. The results of methylation profiles, hypomethylation, and differential methylation analysis are plotted in publication-quality figures. The msPIPE can be easily and conveniently used with a Docker image, which includes all dependent packages and software related to DNA methylation analyses. CONCLUSION: msPIPE is a new end-to-end pipeline designed for methylation calling, profiling, and various types of downstream DNA methylation analyses, leading to the creation of publication-quality figures. msPIPE allows researchers to process and analyze the WGBS data in an easy and convenient way. It is available at https://github.com/jkimlab/msPIPE and https://hub.docker.com/r/jkimlab/mspipe .
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Citosina , Sulfitos , Análise de Sequência de DNA/métodos , Sulfitos/metabolismo , Sequenciamento Completo do Genoma/métodosRESUMO
Tumor progression is profoundly affected by crosstalk between cancer cells and their stroma. In the past decades, the development of bioinformatics and the establishment of organoid model systems have allowed extensive investigation of the relationship between tumor cells and the tumor microenvironment (TME). However, the interaction between tumor cells and the extracellular matrix (ECM) in odontogenic epithelial neoplasms and the ECM remodeling mechanism remain unclear. In the present study, transcriptomic comparison and histopathologic analysis revealed that TME-related genes were upregulated in ameloblastoma compared to in odontogenic keratocysts. Tumoroid analysis indicated that type I collagen is required for ameloblastoma progression. Furthermore, ameloblastoma shows the capacity to remodel the ECM independently of cancer-associated fibroblasts. In conclusion, ameloblastoma-mediated ECM remodeling contributes to the formation of an invasive collagen architecture during tumor progression.
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Colágeno , Microambiente TumoralRESUMO
INTRODUCTION: Recombination-activating gene (Rag) 1 and Rag2, which are essential in V(D)J recombination, play a crucial role in B- and T-cell maturation. METHOD: We investigated the effects of Rag2 deficiency in clustered regularly interspaced short palindromic repeats/Cas9-mediated FVB-Rag2 knockout (KO) and wild-type (WT) mice infected with mouse adenovirus type 1 (MAV-1) via the intranasal route. RESULTS: MAV-1 infection caused more severe histopathological changes in FVB-Rag2 KO mice than in WT mice. FVB-Rag2 KO mice exhibited moderate to severe inflammation on day 4 and severe inflammation on day 8 post infection. In contrast, WT mice showed mild inflammation on day 4 and mild to severe inflammation on day 8 post infection, including interstitial pneumonia and inflammatory cell infiltration in the lungs and liver. Viral loads in the spleen and kidneys were significantly higher in FVB-Rag2 KO mice than in WT mice on day 8 post infection. Levels of cytokines and chemokines, including macrophage inflammatory protein-1α, induced protein 10, interferon (IFN)-α, IFN-γ, and tumor necrosis factor alpha, were upregulated in the spleens of FVB-Rag2 KO mice compared with those of WT mice. The upregulation of several cytokines occurred concurrently with the histopathological changes. MAV-1 infection induced more severe systemic infection in FVB-Rag2 KO mice than in WT mice. CONCLUSION: In mice, Rag2 deficiency induces inflammatory cell recruitment via the upregulation of cytokine and chemokine levels. The MAV-1 infection model can be utilized to assess the efficacy and safety of therapeutic agents for human adenoviral diseases.
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Infecções por Adenoviridae , Citocinas , Adenoviridae/genética , Animais , Citocinas/metabolismo , Proteínas de Ligação a DNA/genética , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Imunodeficiência Combinada SeveraRESUMO
Three-dimensional (3D) multicellular spheroid models can recapitulate the human tumour microenvironment with more accuracy than conventional cell culture models, as they include complex architectural structures and dynamic cellular interactions. Among the diverse platforms for spheroid formation, microfluidic platforms have been extensively applied to study spheroids because they can mimic the in vivo microenvironment. This review provides an overview of the advantages of 3D spheroid cultures with a summary of the recent applications for tumour microenvironment-focused cellular interactions, as well as the studies on spheroids and external stimuli. These 3D tumour spheroid-based microfluidic devices will provide a platform for a better understanding of cellular and external interactions, as well as the discovery of cancer therapeutics.
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Neoplasias , Microambiente Tumoral , Técnicas de Cultura de Células , Humanos , Microfluídica , Neoplasias/patologia , Esferoides Celulares/patologiaRESUMO
Although individually rare, collectively more than 7,000 rare diseases affect about 10% of patients. Each of the rare diseases impacts the quality of life for patients and their families, and incurs significant societal costs. The low prevalence of each rare disease causes formidable challenges in accurately diagnosing and caring for these patients and engaging participants in research to advance treatments. Deep learning has advanced many scientific fields and has been applied to many healthcare tasks. This study reviewed the current uses of deep learning to advance rare disease research. Among the 332 reviewed articles, we found that deep learning has been actively used for rare neoplastic diseases (250/332), followed by rare genetic diseases (170/332) and rare neurological diseases (127/332). Convolutional neural networks (307/332) were the most frequently used deep learning architecture, presumably because image data were the most commonly available data type in rare disease research. Diagnosis is the main focus of rare disease research using deep learning (263/332). We summarized the challenges and future research directions for leveraging deep learning to advance rare disease research.
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Aprendizado Profundo , Doenças do Sistema Nervoso , Humanos , Doenças Raras , Qualidade de Vida , Redes Neurais de ComputaçãoRESUMO
This study aimed to evaluate the effectiveness of using low-level, low-frequency pulsed electromagnetic field (LLLF_PEMF) stimulation to improve atopic dermatitis induced by 2,4-dinitrochlorobenzene (DNCB). Twenty 6-week-old hairless mice were randomly divided into Normal (n = 5), PEMF 15 Hz (n = 5), PEMF 75 Hz (n = 5), and Sham (n = 5) groups. Following the onset of atopic dermatitis symptoms, PEMF groups (15 and 75 Hz) were stimulated with LLLF_PEMF (15 mT) for 8 h per day for 1 week. Sensory evaluation analysis revealed a significant difference between the PEMF 15 Hz group and Sham group (P < 0.05), but these differences were not visually obvious. While both the PEMF and Sham groups had atopic dermatitis lesions, lesion size was significantly smaller in the two PEMF groups than in the Sham group (P < 0.001). Additionally, changes in epithelial thickness because of skin inflammation significantly decreased for both PEMF groups, compared with the Sham group (P < 0.001). In conclusion, these results suggest that PEMF stimulation in vivo triggers electro-chemical reactions that affect immune response. © 2022 Bioelectromagnetics Society.
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Dermatite Atópica , Campos Eletromagnéticos , Animais , Camundongos , Dermatite Atópica/terapia , Campos Eletromagnéticos/efeitos adversosRESUMO
A strategy is reported to improve the detection limits of current giant magnetoresistance (GMR) biosensors by augmenting the effective magnetic moment that the magnetic tags on the biosensors can exert. Magnetic supercluster particles (MSPs), each of which consists of ~ 1000 superparamagnetic cores, are prepared by a wet-chemical technique and are utilized to improve the limit of detection of GMR biosensors down to 17.6 zmol for biotin as a target molecule. This value is more than four orders of magnitude lower than that of the conventional colorimetric assay performed using the same set of reagents except for the signal transducer. The applicability of MSPs in immunoassay is further demonstrated by simultaneously detecting vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) in a duplex assay format. MSPs outperform commercially available magnetic nanoparticles in terms of signal intensity and detection limit.