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1.
Sensors (Basel) ; 24(6)2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38544049

RESUMO

In this work, we propose our newly developed wafer-type plasma monitoring sensor based on a floating-type double probe method that can be useful for two-dimensional (2D) in situ plasma diagnosis within a semiconductor processing chamber. A key achievement of this work is the first realization of an ultra-thin plasma monitoring sensor with a system thickness of ~1.4 mm, which supports a fully automated robot arm transfer capability for in situ plasma diagnosis. To the best of our knowledge, it is the thinnest accomplishment among all wafer-type plasma monitoring sensors. Our proposed sensor is assembled with two Si wafers and SiO2-based probes; accordingly, it makes it possible to monitor the actual dynamics of processing plasmas under electrostatic chucking (ESC) conditions. Also, it allows for the prevention of chamber contamination issues after continuously exposing the radio frequency (RF) to various processing gases. Using a test-bed chamber, we successfully demonstrated the feasibility and system performance of the proposed sensor, including robot arm transfer capability, vacuum and thermal stress durability, and data integrity and reproducibility. Consequently, compared with the conventional plasma diagnostic tools, we expect that our proposed sensor will be highly beneficial for tool-to-tool matching (TTTM) and/or for studying various plasma-related items by more accurately providing the parameters of processing plasmas, further saving both time and manpower resources required for preventive maintenance (PM) routines as well.

2.
Skin Res Technol ; 30(3): e13654, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38504440

RESUMO

BACKGROUND/PURPOSE: Skin elasticity was used to evaluate healthy and diseased skin. Correlation analysis between image texture characteristics and skin elasticity was performed to study the feasibility of assessing skin elasticity using a non-contact method. MATERIALS AND METHODS: Skin images in the near-infrared band were acquired using a hyperspectral camera, and skin elasticity was obtained using a skin elastimeter. Texture features of the mean, standard deviation, entropy, contrast, correlation, homogeneity, and energy were extracted from the acquired skin images, and a correlation analysis with skin elasticity was performed. RESULTS: The texture features, and skin elasticity of skin images in the near-infrared band had the highest correlation on the side of eye and under of arm, and the mean and correlation were features of texture suitable for distinguishing skin elasticity according to the body part. CONCLUSION: In this study, we performed elasticity and correlation analyses for various body parts using the texture characteristics of skin hyperspectral images in the near-infrared band, confirming a significant correlation in some body parts. It is expected that this will be used as a cornerstone of skin elasticity evaluation research using non-contact methods.


Assuntos
Pele , Humanos , Pele/diagnóstico por imagem , Elasticidade
3.
Blood ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38447046

RESUMO

LncRNAs are extensively expressed in eukaryotic cells and have been revealed to be important for regulating cell differentiation. Many lncRNAs have been found to regulate erythroid differentiation in the mouse. However, given the low sequence conservation of lncRNAs between mouse and human, our understanding of lncRNAs in human erythroid differentiation remains incomplete. LncRNAs are often transcribed opposite to protein coding genes and regulate their expression. Here we characterized a human erythrocyte-expressed lncRNA, GATA2AS, which is transcribed opposite to erythroid transcription regulator GATA2. GATA2AS is a 2080 bp-long, primarily nuclear-localized non-coding RNA that is expressed in erythroid progenitor cells and decreases during differentiation. Knockout of GATA2AS in human HUDEP2 erythroid progenitor cells using CRISPR-Cas9 genome editing to remove the transcription start site accelerated erythroid differentiation and dysregulated erythroblast gene expression. We identified GATA2AS as a novel GATA2 and HBG activator. Chromatin Isolation by RNA Purification (ChIRP) showed that GATA2AS binds to thousands of genomic sites and colocalizes at a subset of sites with erythroid transcription factors including LRF and KLF1. RNA-pulldown and RIP confirmed interaction between GATA2AS and LRF and KLF1. ChIP-sequencing showed that knockout of GATA2AS reduces binding of these transcription factors genome wide. ATAC-seq and H3K27ac ChIP-seq showed that GATA2AS is essential to maintain the chromatin regulatory landscape during erythroid differentiation. Knockdown of GATA2AS in human primary CD34+ cells mimicked results in HUDEP2 cells. Overall, our results implicate human-specific lncRNA GATA2AS as a regulator of erythroid differentiation by influencing erythroid transcription factor binding and the chromatin regulatory landscape.

4.
J Gynecol Oncol ; 35(2): e45, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38216137

RESUMO

The Korean Society of Gynecologic Oncology (KSGO) had been making an effort to standardize and enhance the quality of domestic uterine corpus cancer treatment by developing updated clinical practice guidelines in 2021. The KSGO revised the guidelines based on a literature search using 4 key elements: Population, Intervention, Comparison, and Outcome framework. These elements include the evaluation of the efficacy and safety of immune checkpoint inhibitor treatment in recurrent/advanced endometrial cancer patients who have failed platinum-based chemotherapy, as well as the effect of combined treatment with trastuzumab in patients with HER2/neu-positive endometrial cancer. Additionally, the guideline assessed the efficacy and safety of omitting lymph node dissection in low-risk endometrial cancer patients, investigated the effect of sentinel lymph node mapping in early-stage endometrial cancer surgery, addressed the outcome of chemoradiation therapy as a postoperative treatment in patients with advanced (stage III-IVA) endometrial cancer, and explored the impact of initial treatment with immune checkpoint inhibitors on survival in patients with advanced or recurrent endometrial cancer patients.


Assuntos
Neoplasias do Endométrio , Linfonodo Sentinela , Neoplasias Uterinas , Feminino , Humanos , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia , Neoplasias Uterinas/patologia , Neoplasias do Endométrio/patologia , Excisão de Linfonodo , República da Coreia , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela/patologia , Linfonodos/patologia
5.
J Prev Med Public Health ; 57(1): 47-54, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38272016

RESUMO

OBJECTIVES: This study was conducted to systematically summarize trends in research concerning patients with coronavirus disease 2019 (COVID-19) as reported in Korean medical journals. METHODS: We performed a literature search of KoreaMed from January 2020 to September 2022. We included only primary studies of patients with COVID-19. Two reviewers screened titles and abstracts, then performed full-text screening, both independently and in duplicate. We first identified the 5 journals with the greatest numbers of eligible publications, then extracted data pertaining to the general characteristics, study population attributes, and research features of papers published in these journals. RESULTS: Our analysis encompassed 142 primary studies. Of these, approximately 41.0% reported a funding source, while 3.5% disclosed a conflict of interest. In 2020, 42.9% of studies included fewer than 10 participants; however, by 2022, the proportion of studies with over 200 participants had increased to 40.6%. The most common design was the cohort study (48.6%), followed by case reports/series (35.2%). Only 3 randomized controlled trials were identified. Studies most frequently focused on prognosis (58.5%), followed by therapy/intervention (20.4%). Regarding the type of intervention/exposure, therapeutic clinical interventions comprised 26.1%, while studies of morbidity accounted for 13.4%. As for the outcomes measured, 50.7% of studies assessed symptoms/clinical status/improvement, and 14.1% evaluated mortality. CONCLUSIONS: Employing a systematic approach, we examined the characteristics of research involving patients with COVID-19 that was published in Korean medical journals from 2020 onward. Subsequent research should assess not only publication trends over a longer timeframe but also the quality of evidence provided.


Assuntos
COVID-19 , Publicações Periódicas como Assunto , Humanos , Estudos de Coortes , Pacientes , República da Coreia/epidemiologia
6.
J Fungi (Basel) ; 9(12)2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38132760

RESUMO

PURPOSE: The aim of this study is to establish a loop-mediated isothermal amplification (LAMP) method for the rapid detection of vulvovaginal candidiasis (VVC). METHODS: We developed and validated a loop-mediated isothermal amplification (LAMP) method for detecting the most common Candida species associated with VVC, including C. albicans, N. glabratus, C. tropicalis, and C. parapsilosis. We evaluated the specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and Kappa value of the LAMP method to detect different Candida species, using the conventional culture method and internal transcribed spacer (ITS) sequencing as gold standards and smear Gram staining and real-time Rolymerase Chain Reaction (PCR) as controls. RESULTS: A total of 202 cases were enrolled, of which 88 were VVC-positive and 114 were negative. Among the 88 positive patients, the fungal culture and ITS sequencing results showed that 67 cases (76.14%) were associated with C. albicans, 13 (14.77%) with N. glabratus, 5 (5.68%) with C. tropicalis, and 3 (3.41%) with other species. Regarding the overall detection rate, the LAMP method presented sensitivity, specificity, PPV, NPV, and Kappa values of 90.91%, 100%, 100%, 93.4%, and 0.919, respectively. Moreover, the LAMP had a specificity of 100% for C. albicans, N. glabratus, and C. tropicalis, with a sensitivity of 94.03%, 100%, and 80%, respectively. Moreover, the microscopy evaluation had the highest sensitivity, while the real-time PCR was less specific for C. albicans than LAMP. In addition, CHROMagar Candida was inferior to LAMP in detecting non-albicans Candida (NAC) species. CONCLUSIONS: Based on the cost-effective, rapid, and inexpensive characteristics of LAMP, coupled with the high sensitivity and specificity of our VVC-associated Candida detection method, we provided a possibility for the point-of-care testing (POCT) of VVC, especially in developing countries and some laboratories with limited resources.

7.
Biomedicines ; 11(12)2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38137504

RESUMO

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impaired social communication and social interaction, restricted and repetitive behavior, and interests. The core symptoms of ASD are associated with deficits in mesocorticolimbic dopamine pathways that project from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). AST-001 is an investigational product currently in a phase 3 clinical trial for treating the core symptoms of ASD, with L-serine as the API (active pharmaceutical ingredient). Because the causes of ASD are extremely heterogeneous, a single genetic ASD model cannot represent all autism models. In this paper, we used the VPA-exposed model, which is more general and widely used than a single genetic model, but this is also one of the animal models of autism. Herein, we conducted experiments to demonstrate the efficacy of AST-001 as L-Serine that alters the regulation of the firing rate in dopamine neurons by inhibiting small conductance Ca2+-activated K+ channels (SK channels). Through these actions, AST-001 improved sociability and social novelty by rescuing the intrinsic excitabilities of dopamine neurons in VPA-exposed ASD mouse models that showed ASD-related behavioral abnormalities. It is thought that this effect of improving social deficits in VPA-exposed ASD mouse models is due to AST-001 normalizing aberrant SK channel activities that slowed VTA dopamine neuron firing. Overall, these findings suggest that AST-001 may be a potential therapeutic agent for ASD patients, and that its mechanism of action may involve the regulation of dopamine neuron activity and the improvement of social interaction.

8.
Int J Chron Obstruct Pulmon Dis ; 18: 2531-2542, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022823

RESUMO

Purpose: The aim of the study was to use RNA sequencing (RNA-seq) data of lung from chronic obstructive pulmonary disease (COPD) patients to identify the bacteria that are most commonly detected. Additionally, the study sought to investigate the differences in these infections between normal lung tissues and those affected by COPD. Patients and Methods: We re-analyzed RNA-seq data of lung from 99 COPD patients and 93 non-COPD smokers to determine the extent to which the metagenomes differed between the two groups and to assess the reliability of the metagenomes. We used unmapped reads in the RNA-seq data that were not aligned to the human reference genome to identify more common infections in COPD patients. Results: We identified 18 bacteria that exhibited significant differences between the COPD and non-COPD smoker groups. Among these, Yersinia enterocolitica was found to be more than 30% more abundant in COPD. Additionally, we observed difference in detection rate based on smoking history. To ensure the accuracy of our findings and distinguish them from false positives, we double-check the metagenomic profile using Basic Local Alignment Search Tool (BLAST). We were able to identify and remove specific species that might have been misclassified as other species in Kraken2 but were actually Staphylococcus aureus, as identified by BLAST analysis. Conclusion: This study highlighted the method of using unmapped reads, which were not typically used in sequencing data, to identify microorganisms present in patients with lung diseases such as COPD. This method expanded our understanding of the microbial landscape in COPD and provided insights into the potential role of microorganisms in disease development and progression.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/microbiologia , Reprodutibilidade dos Testes , Pulmão/microbiologia , Bactérias/genética , RNA , Análise de Sequência de RNA
9.
Anal Chem ; 95(48): 17450-17457, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-37976220

RESUMO

Feature-based molecular networking (FBMN) is a powerful analytical tool for mass spectrometry (MS)-based untargeted metabolomics data analysis. FBMN plays an important role in drug metabolism studies, enabling the visualization of complex metabolomics data to achieve metabolite characterization. In this study, we propose a strategy for the characterization of glutathione (GSH) adducts formed via in vitro metabolic activation using FBMN assisted by multivariate analysis (MVA). Acetaminophen was used as a model substrate for method development, and the practical potential of the method was investigated by its application to 2-aminophenol (2-AP) and 2,4-dinitrochlorobenzene (DNCB). Two 2-AP GSH adducts and one DNCB GSH adduct were successfully characterized by forming networks with GSH even though the mass spectral information obtained for the parent compound was deficient. False positives were effectively filtered out by the variable influence on projection cutoff criteria obtained from orthogonal partial least-squares-discriminant analysis. The GSH adducts formed by enzymatic or nonenzymatic reactions were intuitively distinguished by the pie chart of FBMN results. In summary, our approach effectively characterizes GSH adducts, which serve as compelling evidence of bioactivation. It can be widely utilized to enhance risk assessment in the context of drug metabolism.


Assuntos
Dinitroclorobenzeno , Glutationa , Dinitroclorobenzeno/metabolismo , Espectrometria de Massas , Glutationa/química , Análise Multivariada , Microssomos Hepáticos/metabolismo
10.
bioRxiv ; 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37808852

RESUMO

The Myb proto-oncogene encodes the transcription factor c-MYB, which is critical for hematopoiesis. Distant enhancers of Myb form a hub of interactions with the Myb promoter. We identified a long non-coding RNA (Myrlin) originating from the -81 kb murine Myb enhancer. Myrlin and Myb are coordinately regulated during erythroid differentiation. Myrlin TSS deletion using CRISPR/Cas9 reduced Myrlin and Myb expression and LDB1 complex occupancy at the Myb enhancers, compromising enhancer contacts and reducing RNA Pol II occupancy in the locus. In contrast, CRISPRi silencing of Myrlin left LDB1 and the Myb enhancer hub unperturbed, although Myrlin and Myb expression were downregulated, decoupling transcription and chromatin looping. Myrlin interacts with the MLL1 complex. Myrlin CRISPRi compromised MLL1 occupancy in the Myb locus, decreasing CDK9 and RNA Pol II binding and resulting in Pol II pausing in the Myb first exon/intron. Thus, Myrlin directly participates in activating Myb transcription by recruiting MLL1.

11.
Nat Commun ; 14(1): 6559, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880248

RESUMO

Adolescent cannabis use increases the risk for cognitive impairments and psychiatric disorders. Cannabinoid receptor type 1 (Cnr1) is expressed not only in neurons and astrocytes, but also in microglia, which shape synaptic connections during adolescence. However, the role of microglia in mediating the adverse cognitive effects of delta-9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, is not fully understood. Here, we report that in mice, adolescent THC exposure produces microglial apoptosis in the medial prefrontal cortex (mPFC), which was exacerbated in a model of 16p11.2 duplication, a representative copy number variation (CNV) risk factor for psychiatric disorders. These effects are mediated by microglial Cnr1, leading to reduction in the excitability of mPFC pyramidal-tract neurons and deficits in social memory in adulthood. Our findings suggest the microglial Cnr1 may contribute to adverse effect of cannabis exposure in genetically vulnerable individuals.


Assuntos
Dronabinol , Microglia , Animais , Camundongos , Agonistas de Receptores de Canabinoides , Variações do Número de Cópias de DNA , Dronabinol/efeitos adversos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/genética , Receptores de Canabinoides/genética
12.
bioRxiv ; 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37546830

RESUMO

Adolescent cannabis use increases the risk for cognitive impairments and psychiatric disorders. Cannabinoid receptor type 1 (Cnr1) is expressed not only in neurons and astrocytes, but also in microglia, which shape synaptic connections during adolescence. Nonetheless, until now, the role of microglia in mediating the adverse cognitive effects of delta-9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, has been unexplored. Here, we report that adolescent THC exposure produces microglial apoptosis in the medial prefrontal cortex (mPFC), which was exacerbated in the mouse model of 16p11.2 duplication, a representative copy number variation (CNV) risk factor for psychiatric disorders. These effects are mediated by microglial Cnr1, leading to reduction in the excitability of mPFC pyramidal-tract neurons and deficits in social memory in adulthood. Our findings highlight the importance of microglial Cnr1 to produce the adverse effect of cannabis exposure in genetically vulnerable individuals.

13.
Int J Gynecol Cancer ; 33(11): 1743-1749, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37541685

RESUMO

OBJECTIVE: Our study aimed to evaluate the incidence of pathological findings in asymptomatic Korean patients with BRCA1/2 pathogenic variants who underwent risk-reducing salpingo-oophorectomy and to assess their long-term prognosis. METHODS: We retrospectively analyzed the medical records of patients with a germinal BRCA1/2 pathologic variant who had undergone risk-reducing salpingo-oophorectomy at Asan Medical Center (Seoul, Korea) between January 2013 and December 2020. All pathologic reports were made based on the sectioning and extensively examining the fimbriated end of the fallopian tube (SEE/FIM) protocol. RESULTS: Out of 243 patients who underwent risk-reducing salpingo-oophorectomy, 121 (49.8%) had a BRCA1 mutation, 119 (48.9%) had a BRCA2 mutation, and three (1.2%) had both mutations. During the procedure, four (3.3%) patients with a BRCA1 mutation were diagnosed with serous tubal intraepithelial carcinoma (STIC) or serous tubal intraepithelial lesion (STIL), and another four patients (3.3%) were diagnosed with occult cancer despite no evidence of malignancy on preoperative ultrasound. In the BRCA2 mutation group, we found one (0.8%) case of STIC, but no cases of STIL or occult cancer. During the median follow-up period of 98 months (range, 44-104) for STIC and 54 months (range, 52-56) for STIL, none of the patients diagnosed with these precursor lesions developed primary peritoneal carcinomatosis. CONCLUSIONS: Risk-reducing salpingo-oophorectomy, in asymptomatic Korean patients with BRCA1/2 pathogenic variants, detected ovarian cancer and precursor lesions, including STIC or STIL. Furthermore, our follow-up period did not reveal any instances of primary peritoneal carcinomatosis, suggesting a limited body of evidence supporting the imperative need for adjuvant treatment in patients diagnosed with these precursor lesions during risk-reducing salpingo-oophorectomy.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Neoplasias Peritoneais , Feminino , Humanos , Salpingo-Ooforectomia , Proteína BRCA1/genética , Ovariectomia , Neoplasias Peritoneais/epidemiologia , Estudos Retrospectivos , Proteína BRCA2/genética , Neoplasias das Tubas Uterinas/patologia , Neoplasias Ovarianas/patologia , Mutação , Prognóstico , Cistadenocarcinoma Seroso/patologia , República da Coreia
14.
Exp Mol Med ; 55(8): 1831-1842, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37582976

RESUMO

We present an in-depth single-cell atlas of in vitro multiculture systems on human primary airway epithelium derived from normal and diseased lungs of 27 individual donors. Our large-scale single-cell profiling identified new cell states and differentiation trajectories of rare airway epithelial cell types in human distal lungs. By integrating single-cell datasets of human lung tissues, we discovered immune-primed subsets enriched in lungs and organoids derived from patients with chronic respiratory disease. To demonstrate the full potential of our platform, we further illustrate transcriptomic responses to various respiratory virus infections in vitro airway models. Our work constitutes a single-cell roadmap for the cellular and molecular characteristics of human primary lung cells in vitro and their relevance to human tissues in vivo.


Assuntos
Células Epiteliais , Pulmão , Humanos , Células Epiteliais/metabolismo , Epitélio , Diferenciação Celular/fisiologia , Organoides
15.
J Control Release ; 361: 443-454, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37558053

RESUMO

Triple-negative breast cancer (TNBC) is highly aggressive and has no standard treatment. Although being considered as an alternative to conventional treatments for TNBC, immunotherapy has to deal with many challenges that hinder its efficacy, particularly the poor immunogenic condition of the tumor microenvironment (TME). Herein, we designed a liposomal nanoparticle (LN) platform that delivers simultaneously toll-like receptor 7 (imiquimod, IQ) and toll-like receptor 3 (poly(I:C), IC) agonists to take advantage of the different toll-like receptor (TLR) signaling pathways, which enhances the condition of TME from a "cold" to a "hot" immunogenic state. The optimized IQ/IC-loaded LN (IQ/IC-LN) was effectively internalized by cancer cells, macrophages, and dendritic cells, followed by the release of the delivered drugs and subsequent stimulation of the TLR3 and TLR7 signaling pathways. This stimulation encouraged the secretion of type I interferon (IFN-α, IFN-ß) and CXCLl0, a T-cell and antigen-presenting cells (APCs) recruitment chemokine, from both cancer cells and macrophages and polarized macrophages to the M1 subtype in in vitro studies. Notably, systemic administration of IQ/IC-LN allowed for the high accumulation of drug content in the tumor, followed by the effective uptake by immune cells in the TME. IQ/IC-LN treatment comprehensively enhanced the immunogenic condition in the TME, which robustly inhibited tumor growth in tumor-bearing mice. Furthermore, synergistic antitumor efficacy was obtained when the IQ/IC-LN-induced immunogenic state in TME was combined with anti-PD1 antibody therapy. Thus, our results suggest the potential of combining 2 TLR agonists to reform the TME from a "cold" to a "hot" state, supporting the therapeutic efficacy of immune checkpoint inhibitors.


Assuntos
Receptor 3 Toll-Like , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adjuvantes Imunológicos , Lipossomos , Poli I-C/uso terapêutico , Imunoterapia/métodos , Microambiente Tumoral
16.
Nucl Med Commun ; 44(11): 1005-1010, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37578339

RESUMO

OBJECTIVE: High-grade neuroendocrine cervical cancer (HGNECC) is a rare and aggressive cervical cancer subtype. In this study, we aimed to evaluate the prognostic value of fluorodeoxyglucose-PET/computed tomography (CT) parameters for HGNECC. MATERIALS AND METHODS: This single-center retrospective study included 29 patients with HGNECC who underwent fluorodeoxyglucose-PET/CT scan followed by surgery between 2006 and 2016. RESULTS: The median follow-up period was 40 (range, 4-184) months. After surgery, the resection margins were tumor-negative in 28 patients (96.6%), 8 (27.6%) patients had parametrial tumor invasion, and 7 patients (24.1%) tested positive for lymph node metastasis. The tumor recurred in 20 patients (69%) and 18 patients (62.1%) died during the observation period. In the univariate analyses, age and total lesion glycolysis (TLG) were associated with worse disease-free survival (DFS) (age, hazard ratio 1.056, 95% CI 1.014-1.100, P  = 0.009; TLG2.5, hazard ratio 1.003, 95% CI 1-1.006, P  = 0.033; and TLG3.0, hazard ratio 1.003, 95% CI 1-1.006, P  = 0.034). In the multivariate analyses, older age and higher TLG3.0 were identified as independent poor prognostic factors for DFS (age, hazard ratio 1.058, 95% CI 1.014-1.104, P  = 0.009; TLG3.0, hazard ratio 1.004, 95% CI 1-1.007, P  = 0.033), while resection margin involvement was identified as an independent factor to predict poor overall survival (hazard ratio 20.717, 95% CI 1.289-332.964, P  = 0.032). CONCLUSION: Among the preoperative fluorodeoxyglucose-PET/CT parameters, TLG3.0 may be useful for predicting DFS in patients with HGNECC.

17.
Sci Adv ; 9(32): eadg6319, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37556544

RESUMO

Underrepresentation of non-European (EUR) populations hinders growth of global precision medicine. Resources such as imputation reference panels that match the study population are necessary to find low-frequency variants with substantial effects. We created a reference panel consisting of 14,393 whole-genome sequences including more than 11,000 Asian individuals. Genome-wide association studies were conducted using the reference panel and a population-specific genotype array of 72,298 subjects for eight phenotypes. This panel yields improved imputation accuracy of rare and low-frequency variants within East Asian populations compared with the largest reference panel. Thirty-nine previously unidentified associations were found, and more than half of the variants were East Asian specific. We discovered genes with rare protein-altering variants, including LTBP1 for height and GPR75 for body mass index, as well as putative regulatory mechanisms for rare noncoding variants with cell type-specific effects. We suggest that this dataset will add to the potential value of Asian precision medicine.


Assuntos
População do Leste Asiático , Estudo de Associação Genômica Ampla , Humanos , Genoma Humano , Polimorfismo de Nucleotídeo Único , Genótipo , Receptores Acoplados a Proteínas G/genética
19.
Environ Microbiol Rep ; 15(6): 708-715, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37231623

RESUMO

Colony formation is key to many ecological and biotechnological processes. In its early stages, colony formation involves the concourse of a number of physical and biological parameters for generation of a distinct 3D structure-the specific influence of which remains unclear. We focused on a thus far neglected aspect of the process, specifically the consequences of the differential pressure experienced by cells in the middle of a colony versus that endured by bacteria located in the growing periphery. This feature was characterized experimentally in the soil bacterium Pseudomonas putida. Using an agent-based model we recreated the growth of microcolonies in a scenario in which pressure was the only parameter affecting proliferation of cells. Simulations exposed that, due to constant collisions with other growing bacteria, cells have virtually no free space to move sideways, thereby delaying growth and boosting chances of overlapping on top of each other. This scenario was tested experimentally on agar surfaces. Comparison between experiments and simulations suggested that the inside/outside differential pressure determines growth, both timewise and in terms of spatial directions, eventually moulding colony shape. We thus argue that-at least in the case studied-mere physical pressure of growing cells suffices to explain key dynamics of colony formation.


Assuntos
Pressão , Pseudomonas putida , Pseudomonas putida/crescimento & desenvolvimento
20.
Physiol Rep ; 11(6): e15655, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36967473

RESUMO

Marine teleosts ingest large amounts of seawater containing various ions, including 0.4 mM boric acid, which can accumulate at toxic levels in the body. However, the molecular mechanisms by which marine teleosts absorb and excrete boric acid are not well understood. Aquaporins (Aqps) are homologous to the nodulin-like intrinsic protein (NIP) family of plant boric acid channels. To investigate the potential roles of Aqps on boric acid transport across the plasma membrane in marine teleosts, we analyzed the function of Aqps of Japanese pufferfish (Takifugu rubripes) expressed in Xenopus laevis oocytes. Takifugu genome database contains 16 genes encoding the aquaporin family members (aqp0a, aqp0b, aqp1aa, aqp1ab, aqp3a, aqp4a, aqp7, aqp8bb, aqp9a, aqp9b, aqp10aa, aqp10bb, aqp11a, aqp11b, aqp12, and aqp14). When T. rubripes Aqps (TrAqps) were expressed in X. laevis oocytes, a swelling assay showed that boric acid permeability was significantly increased in oocytes expressing TrAqp3a, 7, 8bb, 9a, and 9b. The influx of boric acid into these oocytes was also confirmed by elemental quantification. Electrophysiological analysis using a pH microelectrode showed that these TrAqps increase B(OH)3 permeability. These results indicate that TrAqp3a, 7, 8bb, 9a, and 9b act as boric acid transport systems, likely as channels, in marine teleosts.


Assuntos
Aquaporinas , Animais , Xenopus laevis/metabolismo , Aquaporinas/genética , Aquaporinas/metabolismo , Oócitos/metabolismo , Ácidos Bóricos/metabolismo
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