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1.
Brain Res Bull ; 217: 111074, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39245352

RESUMEN

OBJECTIVE: To construct relatively objective, atlas-based multivariate models for predicting early aphasia severity after stroke, using structural magnetic resonance imaging. METHODS: We analyzed the clinical and imaging data of 46 patients with post-stroke aphasia. The aphasia severity was identified with a Western Aphasia Battery Aphasia Quotient. The assessments of stroke lesions were indicated by the lesion load of both the cortical language areas (Areas-LL) and four white matter tracts (i.e., the superior longitudinal fasciculus, SLF-LL; the inferior frontal occipital fasciculi, IFOF-LL; the inferior longitudinal, ILF-LL; and the uncinate fasciculi, UF-LL) extracted from human brain atlas. Correlation analyses and multiple linear regression analyses were conducted to evaluate the correlations between demographic, stroke- and lesion-related variables and aphasia severity. The predictive models were then established according to the identified significant variables. Finally, the receiver operating characteristic (ROC) curve was utilized to assess the accuracy of the predictive models. RESULTS: The variables including Areas-LL, the SLF-LL, and the IFOF-LL were significantly negatively associated with aphasia severity (p < 0.05). In multiple linear regression analyses, these variables accounted for 59.4 % of the variance (p < 0.05). The ROC curve analyses yielded the validated area under the curve (AUC) 0.84 both for Areas-LL and SLF-LL and 0.76 for IFOF-LL, indicating good predictive performance (p < 0.01). Adding the combination of SLF-LL and IFOF-LL to this model increased the explained variance to 62.6 % and the AUC to 0.92. CONCLUSIONS: The application of atlas-based multimodal lesion assessment may help predict the aphasia severity after stroke, which needs to be further validated and generalized for the prediction of more outcome measures in populations with various brain injuries.

2.
Curr Gene Ther ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39289931

RESUMEN

BACKGROUND: Ovarian cancer is associated with a high mortality rate. Oxidative Phosphorylation (OXPHOS) is an active metabolic pathway in cancer; nevertheless, its role in ovarian cancer continues to be ambiguous. Therefore, the objective of this study was to identify the prognostic value of OXPHOS-related genes and the immune landscape in ovarian cancer. METHODS: We obtained public ovarian cancer-related datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and recognized OXPHOS-related genes from the GeneCards database and literature. Cox regression analyses were conducted to identify prognostic OXPHOS-related genes and develop a prognostic nomogram based on the OXPHOS score and clinicopathological features of patients. Functional enrichment analyses were employed to identify related processes. RESULTS: A 12-gene signature was identified to classify the ovarian cancer patients into high- and low-risk groups. The Immunophenoscore (IPS) was higher in the OXPHOS score-high group than in the OXPHOS score-low group, suggesting a better response to immune checkpoint inhibitors. Functional enrichment analyses unveiled that OXPHOS-related genes were considerably abundant in a series of immune processes. The calibration curves of the constructed prognostic nomograms at 1, 2, and 3 years exhibited strong concordance between the anticipated and observed survival probabilities of ovarian cancer patients. CONCLUSION: We have constructed a prognostic model containing 12 OXPHOS-related genes and demonstrated its strong predictive value in ovarian cancer patients. OXPHOS has been found to be closely linked to immune infiltration and the reaction to immunotherapy, which may contribute to improving individualized treatment and prognostic evaluation in ovarian cancer.

3.
Onco Targets Ther ; 17: 755-763, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39282132

RESUMEN

Objective: PIK3CA-mutant non-small-cell lung cancer (NSCLC) is associated with other genetic mutations and may influence treatment strategies and clinical outcomes. We aimed to characterize PIK3CA mutations co-occurring with several major driver mutations using data from published cohorts and our medical center. Materials and Methods: We analyzed NSCLC patients harboring PIK3CA mutations from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering (MSK) databases and retrospectively identified NSCLC patients with PIK3CA-mutants at a single medical center from our electronic records. The Log rank test was used to determine the association between PIK3CA mutations and overall survival (OS) in NSCLC patients. Results: Common hotspot mutations in PIK3CA were found in exon 9 (c.1633G > A, E545K, and c.1624G > A, E542K) and exon 20 (c.3140A > G, H1047R) in all cohorts. Co-occurring mutations of PIK3CA with EGFR, KRAS, and TP53 have been frequently observed in patients with NSCLC, with different percentages in these datasets generated by different background. PIK3CA mutations were observed to be significantly associated with poor OS in lung adenocarcinomas patients in the MSKCC cohort (hazard ratio [HR] = 0.519, 95% confidence interval [CI] = 0.301-0.896; P <0.05). Conclusion: PIK3CA co-occurring mutations in other genes may represent distinct subsets of NSCLC. Further elucidation of the roles of PIK3CA hotspot mutations combined with other driver mutations, including EGFR and KRAS, is needed to guide effective treatment in patients with advanced NSCLC.

4.
Heliyon ; 10(17): e37617, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39290278

RESUMEN

Background: Ferroptosis is a new type of programmed cell death. Although ferroptosis has been studied in various aspects, there has been no visual analysis of ferroptosis in coronavirus disease 2019 (COVID-19) to date. It is still a global health concern of the COVID-19 pandemic worldwide, three years after its outbreak. Yet the emergence of the mutant strain Omicron has caused a fourth wave of infections in many countries. The pathogenesis of COVID-19 is still undergoing extensive exploration, which holds paramount importance in mitigating future epidemics. Methods: For this study, CiteSpace 6.2 R4 software was used for bibliometric and visual atlas analysis of ferroptosis-related research, and the Genecards database was used to mine ferroptosis and COVID-19-related genes. Results: We found increasing studies about ferroptosis. China and the United States have demonstrated robust scientific innovation over recent years, with extensive collaboration between their institutions and authors. Ferroptosis and COVID-19 were seen to have 13 shared genes, which may be new targets for the treatment of COVID-19 in the future. Most of the shared genes are enriched in tumor necrosis factor (TNF) pathways. The majority of those genes are up-regulated under the cellular response to oxidative stress. Genes including Tumour necrosis factor (TNF), RELA proto-oncogene (RELA), Activating transcription factor 4 (ATF4), Cytochrome b-245 beta chain (CYBB), Jun proto-oncogene (JUN), Mitogen-activated protein kinase 1 (MAPK1) and Heme oxygenase 1 (HMOX1), maybe a breakthrough for ferroptosis and COVID-19. Whilst previous research has shown there to be a relationship between ferroptosis and COVID-19, the specific role of ferroptosis remained unclear. Our study aimed to analyze the research status of ferroptosis and its relationship with COVID-19, to provide a useful reference for further prevention and treatment of COVID-19. Overall, uncovering the role of ferroptosis in SARS-CoV-2 infection is important for the development of new treatment strategies for COVID-19.

5.
Plant Cell ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39283506

RESUMEN

The geometric shape and arrangement of individual cells play a role in shaping organ functions. However, analyzing multicellular features and exploring their connectomes in centimeter-scale plant organs remain challenging. Here, we established a set of frameworks named Large-Volume Fully Automated Cell Reconstruction (LVACR), enabling the exploration of three-dimensional (3D) cytological features and cellular connectivity in plant tissues. Through benchmark testing, our framework demonstrated superior efficiency in cell segmentation and aggregation, successfully addressing the inherent challenges posed by light sheet fluorescence microscopy (LSFM) imaging. Using LVACR, we successfully established a cell atlas of different plant tissues. Cellular morphology analysis revealed differences of cell clusters and shapes in between different poplar (P. simonii Carr. and P. canadensis Moench.) seeds, whereas topological analysis revealed that they maintained conserved cellular connectivity. Furthermore, LVACR spatiotemporally demonstrated an initial burst of cell proliferation, accompanied by morphological transformations at an early stage in developing the shoot apical meristem. During subsequent development, cell differentiation produced anisotropic features, thereby resulting in various cell shapes. Overall, our findings provided valuable insights into the precise spatial arrangement and cellular behavior of multicellular organisms, thus enhancing our understanding of the complex processes underlying plant growth and differentiation.

6.
BMC Cancer ; 24(1): 1144, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39272022

RESUMEN

BACKGROUND: HPV status in a subset of HNSCC is linked with distinct treatment outcomes. Present investigation aims to elucidate the distinct clinicopathological features of HPV-positive and HPV-negative HNSCC and investigate their association with the HNSCC patient survival. MATERIALS AND METHODS: The total RNA of exosomes from HPV-positive (93VU147T) and HPV-negative (OCT-1) HNSCC cells was isolated, and the transcripts were estimated using Illumina HiSeq X. The expression of altered transcripts and their clinical relevance were further analyzed using publicly available cancer transcriptome data from The Cancer Genome Atlas (TCGA). RESULTS: Transcriptomic analyses identified 3785 differentially exported transcripts (DETs) in HPV-positive exosomes compared to HPV-negative exosomes. DETs that regulate the protein machinery, cellular redox potential, and various neurological disorder-related pathways were over-represented in HPV-positive exosomes. TCGA database revealed the clinical relevance of altered transcripts. Among commonly exported abundant transcripts, SGK1 and MAD1L1 showed high expression, which has been correlated with poor survival in HNSCC patients. In the top 20 DETs of HPV-negative exosomes, high expression of FADS3, SGK3, and TESK2 correlated with poor survival of the HNSCC patients in the TCGA database. CONCLUSION: Overall, our study demonstrates that HPV-positive and HPV-negative cells' exosomes carried differential transcripts cargo that may be related to pathways associated with neurological disorders. Additionally, the altered transcripts identified have clinical relevance, correlating with patient survival in HNSCC, thereby highlighting their potential as biomarkers and as therapeutic targets.


Asunto(s)
Exosomas , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Exosomas/metabolismo , Exosomas/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/virología , Neoplasias de Cabeza y Cuello/metabolismo , Masculino , Femenino , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Persona de Mediana Edad , Línea Celular Tumoral , Transcriptoma , Pronóstico , Anciano
7.
Diagnostics (Basel) ; 14(17)2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39272720

RESUMEN

This study aimed to compare and evaluate the accuracy of the Demirjian (DE) and the London Atlas (LAE) dental age estimation methods in a Saudi population sample. This retrospective cross-sectional study used digital radiographs from electronic health records in three different dental institutes. In total, 357 male and 354 female (ages 5-15 years) digital orthopantomograms were selected for age estimation. The mean difference between the chronological age (CA) and age estimation method among males and females was 0.03 ± 0.34 and 0.00 ± 0.34, respectively, for LAE and 0.55 ± 0.84 and 0.76 ± 0.51, respectively, for DE. The mean difference between the LAE and DE methods among males and females was 0.52 ± 0.89 and -0.76 ± 0.57, respectively. No statistically significant difference between CA and LAE was found in either males (p = 0.079) or females (p = 0.872). A statistically significant difference was found between CA and DE in both genders (p < 0.001). A statistically significant difference was found between the LAE and DE groups (p < 0.001) in both genders. An overestimation of dental age was observed with DE compared with that in CA. LAE showed higher accuracy than CA, with no clinically significant difference. Although the difference between the LAE and DE methods was insignificant, the LAE method proved to be more accurate.

8.
Psychiatry Res Neuroimaging ; 344: 111885, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39217669

RESUMEN

BACKGROUND: Current models of major depressive disorder (MDD) primarily focus on the structural and functional changes in key prefrontal areas responsible for emotional regulation. Among these regions some sections such as the dorsal prefrontal area, has received limited attention regarding its structural abnormalities in MDD. This study aims to evaluate volumetric abnormalities in brain regions associated with markers of depression severity and episode frequency. METHODS: The study included 33 MDD patients and 33 healthy subjects. Using an atlas-based method, we measured the volumes of several key brain regions based on MRI data. The regions of interest included prefrontal and posterior sections of the middle frontal gyrus (MFG) and superior frontal gyrus (SFG). Additionally, we evaluated the volumes of the dorsal anterior cingulate cortex (dACC), perigenual (rostral) anterior cingulate cortex (pgACC), subgenual cingulate cortex (sgACC), posterior cingulate cortex (PCC), hippocampus (HPC), and parahippocampus (paraHPC). Hamilton Depression Scale (HAM-D) scores and count of the depressive episodes of patients were also obtained. A regression analysis with sex as the confounding factor has been made. RESULTS: Analysis of covariances, controlling for sex, showed significant atrophy in the sgACC in the depression group: F(1, 63) = 4.013, p = 0.049 (left) and F(1, 63) = 8.786, p < 0.004 (right). Poisson regression, also controlling for sex, found that each additional depressive episode was associated with a significant reduction in left posterior MFG volume (0.952 times, 95 % CI, 0.906 to 1.000; p = 0.049). CONCLUSIONS: Findings in this study highlight the structural abnormalities in MDD patients in correlation to either current depression severity or chronicity of the disease.


Asunto(s)
Atrofia , Trastorno Depresivo Mayor , Imagen por Resonancia Magnética , Corteza Prefrontal , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/patología , Trastorno Depresivo Mayor/psicología , Masculino , Femenino , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/patología , Adulto , Atrofia/patología , Persona de Mediana Edad , Atlas como Asunto , Índice de Severidad de la Enfermedad
9.
bioRxiv ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39253414

RESUMEN

Scientific interest in the cerebellum has surged in the last few decades with an emerging consensus on a multifaceted functionality and intricate, but not yet fully understood, functional topography over the cerebellar cortex. To further refine this structure-function relationship and quantify its inter-subject variability, a high-resolution digital anatomical atlas is fundamental. Using a combination of manual labeling and image processing, we turned a recently published reconstruction of the human cerebellum, the first such reconstruction fine enough to resolve the individual folia, into a digital atlas with both surface and volumetric representations. Its unprecedented granularity (0.16 mm) and detailed expert labeling make the atlas usable as an anatomical ground truth, enabling new ways of analyzing and visualizing cerebellar data through its digital format.

10.
Front Cell Dev Biol ; 12: 1444706, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39268087

RESUMEN

Yaks (Bos grunniens) exhibit exceptional adaptation to the challenging high-altitude environment of the Qinghai-Tibetan plateau, making them the sole bovine species capable of thriving in such exreme conditions. Investigating the cellular and molecular characteristics of yak ovaries across different reproductive states is crucial for gaining insight into their ovarian functions. Herein, the cellular atlases of yak ovaries in different reproductive states were depicted by single-cell RNA-sequencing (scRNA-seq). The cellular atlases of the ovaries were established by identifying specific gene expression patterns of various cell types, including granulosa cells, theca cells, stromal cells, smooth muscle cells, endothelial cells, glial cell, macrophages, natural killer cells, and proliferating cells. The cellular compositions of the ovaries vary among different reproductive states. Furthermore, the granulosa cells comprise six cell subtypes, while theca cells consist of eight cell subtypes. The granulosa cells and theca cells exhibit distinct biological functions throughout different reproductive states. The two cell types were aligned along their respective pseudotime trajectories. Moreover, a cell-to-cell communication network was constructed among distinct cell types within the ovary, spanning the three reproductive states. Notably, during the estrus period, the granulosa cells demonstrated more prominent interactions with other cell types compared to the remaining reproductive states.

11.
Oncol Lett ; 28(5): 510, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39268167

RESUMEN

Thyroid cancer (THCA) is a malignant tumor that affects the endocrine system. At present, an effective treatment for THCA remains elusive, particularly for medullary carcinoma and undifferentiated carcinoma, due to the lack of suitable medications and prognostic markers. Patient RNA-sequencing and clinical data were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Protein-protein interaction analyses were performed for differentially expressed genes related to THCA. Moreover, the associations between fibronectin 1 (FN1), clinical data, immune checkpoint genes and immune cell infiltration was assessed. The potential functional role of the FN1 gene was evaluated through gene set enrichment analysis. Immunohistochemistry was used to assess FN1 expression in 103 cases of THCA, comprising 32 with papillary carcinoma, 30 with follicular carcinoma, 35 with medullary carcinoma and 6 with undifferentiated carcinoma. Finally, 11 co-expression modules were constructed and the expression of five identified hub genes (FN1, mucin-1, keratin 19, intracellular adhesion molecule 1 and neural cell adhesion molecule) were evaluated. The results demonstrated that higher FN1 gene expression levels were strongly associated with a higher pathologic stage and tumor stage, and were significantly associated with immune cell infiltration in THCA. Significant increases in FN1 protein expression levels were noted among patients diagnosed with four types of THCA, comprising papillary carcinoma, follicular carcinoma, medullary carcinoma and undifferentiated carcinoma. Patients diagnosed with medullary carcinoma and undifferentiated carcinoma, and with low FN1 expression levels, exhibited a significant survival advantage compared with those with high FN1 expression levels. In conclusion, the present study identified five hub genes involved in the onset and progression of THCA. Furthermore, FN1 could serve as a candidate biomarker and a therapeutic target for THCA and may be a key gene mediating THCA immune infiltration.

12.
Cureus ; 16(8): e66585, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39252738

RESUMEN

Type II odontoid fracture, classified by Anderson and D'Alonzo, is the most common traumatic injury to the odontoid process. Surgical management of this lesion is particularly challenging in underresourced countries. This study aims to report the preliminary experience of the Kinshasa University Teaching Hospital in Kinshasa, Democratic Republic of the Congo, particularly using adaptive techniques. Three patients, aged 22, 30, and 32 years, respectively, were admitted to the neurosurgery department with Anderson and D'Alonzo type II odontoid fractures as confirmed by CT scan imaging. The first two patients underwent anterior odontoid fixation using a non-cannulated orthopaedic screw with an image intensifier. In the third case, partial resection of the C1 posterior arch was performed, followed by immobilisation using a rigid Philadelphia neck brace. Postoperative follow-up in all three cases was uneventful, and neurological outcomes were satisfactory. Odontoid surgery remains challenging for developing countries. The use of a non-cannulated orthopaedic screw for anterior fixation and posterior spinal cord decompression via partial resection of the C1 posterior arch, followed by external cervical immobilisation with a rigid neck brace for neglected fractures, could be effective alternatives to conventional surgical techniques. However, randomised multicentre studies are required to confirm the efficacy and safety of these techniques.

14.
Breast Cancer Res ; 26(1): 129, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232806

RESUMEN

BACKGROUND: The internal heterogeneity of breast cancer, notably the tumor microenvironment (TME) consisting of malignant and non-malignant cells, has been extensively explored in recent years. The cells in this complex cellular ecosystem activate or suppress tumor immunity through phenotypic changes, secretion of metabolites and cell-cell communication networks. Macrophages, as the most abundant immune cells within the TME, are recruited by malignant cells and undergo phenotypic remodeling. Tumor-associated macrophages (TAMs) exhibit a variety of subtypes and functions, playing significant roles in impacting tumor immunity. However, their precise subtype delineation and specific function remain inadequately defined. METHODS: The publicly available single-cell transcriptomes of 49,141 cells from eight breast cancer patients with different molecular subtypes and stages were incorporated into our study. Unsupervised clustering and manual cell annotation were employed to accurately classify TAM subtypes. We then conducted functional analysis and constructed a developmental trajectory for TAM subtypes. Subsequently, the roles of TAM subtypes in cell-cell communication networks within the TME were explored using endothelial cells (ECs) and T cells as key nodes. Finally, analyses were repeated in another independent publish scRNA datasets to validate our findings for TAM characterization. RESULTS: TAMs are accurately classified into 7 subtypes, displaying anti-tumor or pro-tumor roles. For the first time, we identified a new TAM subtype capable of proliferation and expansion in breast cancer-TUBA1B+ TAMs playing a crucial role in TAMs diversity and tumor progression. The developmental trajectory illustrates how TAMs are remodeled within the TME and undergo phenotypic and functional changes, with TUBA1B+ TAMs at the initial point. Notably, the predominant TAM subtypes varied across different molecular subtypes and stages of breast cancer. Additionally, our research on cell-cell communication networks shows that TAMs exert effects by directly modulating intrinsic immunity, indirectly regulating adaptive immunity through T cells, as well as influencing tumor angiogenesis and lymphangiogenesis through ECs. CONCLUSIONS: Our study establishes a precise single-cell atlas of breast cancer TAMs, shedding light on their multifaceted roles in tumor biology and providing resources for targeting TAMs in breast cancer immunotherapy.


Asunto(s)
Neoplasias de la Mama , Análisis de la Célula Individual , Transcriptoma , Microambiente Tumoral , Macrófagos Asociados a Tumores , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Femenino , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Comunicación Celular/inmunología , Biomarcadores de Tumor/genética , Células Endoteliales/metabolismo , Células Endoteliales/patología
15.
Front Mol Biosci ; 11: 1425422, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234567

RESUMEN

Introduction: Esophageal squamous cell carcinoma (ESCC) accounts for over 90% of all esophageal tumors. However, the molecular mechanism underlying ESCC development and prognosis remains unclear, and there are still no effective molecular biomarkers for diagnosing or predicting the clinical outcome of patients with ESCC. Here, we used bioinformatics analysis to identify potential biomarkers and therapeutic targets for ESCC. Methodology: Differentially expressed genes (DEGs) between ESCC and normal esophageal tissue samples were obtained by comprehensively analyzing publicly available RNA-seq datasets from the TCGA and GTEX. Gene Ontology (GO) annotation and Reactome pathway analysis identified the biological roles of the DEGs. Moreover, the Cytoscape 3.10.1 platform and subsidiary tools such as CytoHubba were used to visualize the DEGs' protein-protein interaction (PPI) network and identify hub genes, Furthermore our results are validated by using Single-cell RNA analysis. Results: Identification of 2524 genes exhibiting altered expression enriched in pathways including keratinization, epidermal cell differentiation, G alpha(s) signaling events, and biological process of cell proliferation and division, extracellular matrix (ECM) disassembly, and muscle function. Moreover, upregulation of hallmarks E2F targets, G2M checkpoints, and TNF signaling. CytoHubba revealed 20 hub genes that had a valuable influence on the progression of ESCC in these patients. Among these, the high expression levels of four genes, CDK1 MAD2L1, PLK1, and TOP2A, were associated with critical dependence for cell survival in ESCC cell lines, as indicated by CRISPR dependency scores, gene expression data, and cell line metadata. We also identify the molecules targeting these essential hub genes, among which GSK461364 is a promising inhibitor of PLK1, BMS265246, and Valrubicin inhibitors of CDK1 and TOP2A, respectively. Moreover, we identified that elevated expression of MMP9 is associated with worse overall survival in ESCC patients, which may serve as potential prognostic biomarker or therapeutic target for ESCC. The single-cell RNA analysis showed MMP9 is highly expressed in myeloid, fibroblast, and epithelial cells, but low in T cells, endothelial cells, and B cells. This suggests MMP9's role in tumor progression and matrix remodeling, highlighting its potential as a prognostic marker and therapeutic target. Discussion: Our study identified key hub genes in ESCC, assessing their potential as therapeutic targets and biomarkers through detailed expression and dependency analyses. Notably, MMP9 emerged as a significant prognostic marker with high expression correlating with poor survival, underscoring its potential for targeted therapy. These findings enhance our understanding of ESCC pathogenesis and highlight promising avenues for treatment.

16.
Antimicrob Agents Chemother ; : e0067024, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39254297

RESUMEN

Ceftazidime-avibactam (CZA) and ceftolozane-tazobactam (C/T) are important agents for treating multidrug-resistant P. aeruginosa infections. In this study, we evaluated the molecular characteristics of 300 globally collected clinical P. aeruginosa isolates non-susceptible (NS) to CZA, C/T, or both agents. Isolates were CZA-NS and C/T-NS (n = 57), CZA-susceptible (S) and C/T-NS (n = 145), or CZA-NS and C/T-S (n = 98) selected from the Antimicrobial Testing Leadership and Surveillance (ATLAS) surveillance program from 2020 to 2021. Characterization was by whole-genome sequencing. Analysis was performed to identify ß-lactamase genes and mutations that impact efflux regulation, AmpC regulation, and target binding (PBP3). Of the 57 CZA-NS+C/T-NS isolates, 64.9% carried a metallo-ß-lactamase (MBL), and a cumulative 84.2% carried any non-intrinsic ß-lactamase [i.e., not Pseudomonas-derived cephalosporinase (PDC) or OXA-50-like]. Of the 145 CZA-S+C/T-NS isolates, 26.2% carried an extended-spectrum ß-lactamase (ESBL) and no carbapenemase, 17.9% carried a serine-carbapenemase, and 42.1% were negative for non-intrinsic ß-lactamases. Of 98 CZA-NS+C/T-S isolates, 34.7% carried mutations previously described as causing an upregulation of the MexAB-OprM efflux pump, while only 9.2% carried a non-intrinsic ß-lactamase, and no resistance mechanism was identified in 29.6% of these isolates. MBLs were present in most isolates NS to both agents. More than half of the CZA-S+C/T-NS isolates carried serine ß-lactamases. The most frequently identified resistance mechanism identified in CZA-NS+C/T-S isolates was a marker indicating the upregulation of MexAB-OprM. No mechanism was identified that is thought to support resistance to these agents in numerous isolates. This may be due in part to the fact that whole genome sequencing (WGS) cannot directly measure gene expression of chromosomal resistance mechanisms.

17.
Front Neurol ; 15: 1391799, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39099782

RESUMEN

Background: Treating wide-neck bifurcated cerebral aneurysms (WNBAs) using various techniques and new devices has shown favorable outcomes. However, endovascular coiling can be technically challenging when the aneurysm neck is incorporated into the parent vessel. Furthermore, although recent research has reported favorable outcomes of Neuroform Atlas stent (NAS)-assisted coiling, broad inclusion criteria have hampered precise evaluations of their effectiveness and safety for treating complex WNBAs. Therefore, this study evaluated whether the use of a single NAS is a safe and effective approach for treating complex WNBAs. Methods: We treated 76 complex WNBAs (unruptured, n = 49; ruptured, n = 27) using single NAS-assisted coil embolization and retrospectively analyzed the clinical and angiographic outcomes. Results: In a cohort of 68 patients (mean age, 58.3 ± 11.6 years; males n = 20, 29.4%; females, n = 48, 70.6%), 76 stents were successfully delivered to the target aneurysms, yielding a technical success rate of 98.6%. Complete occlusion was evident in 59 (77.6%) of 76 aneurysms, with neck remnants found in 16 (21.1%) and partial occlusion in 1 (1.3%). Treatment-related morbidities comprised one branch occlusion and one parenchymal hemorrhage. However, no new neurological symptoms of unruptured aneurysms were evident at discharge. The outcomes of 20 of the 27 ruptured aneurysms were favorable (Glasgow Outcome Scale scores of 4 or 5) at the final follow-up assessment (mean 12.2 [6-29] months), except for one initial subarachnoid hemorrhage. Post-treatment angiography revealed complete occlusion in 89.1%, neck remnants in 7.8%, and incomplete occlusion in 3.1% of the aneurysms. Approximately 88.2% of the patients were assessed at least once by follow-up diagnostic or magnetic resonance angiography (mean, 12.5 ± 4.3 [range, 6-29] months), with five (7.8%) minor and two (3.1%) major recurrences. Conclusion: A single NAS is safe and effective for treating WNBAs incorporated into parent vessels.

18.
Neurosurg Rev ; 47(1): 404, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39103656

RESUMEN

Basilar invagination (BI) is a common deformity. This study aimed to quantitatively evaluate the height of clivus and atlanto-occipital lateral mass (LM) in patients with BI with or without atlas occipitalization (AOZ). We evaluated 166 images of patients with BI and of controls. Seventy-one participants were control subjects (group A), 68 had BI with AOZ (group B), and 27 had BI without AOZ (group C). Parameters were defined and measured for comparisons across the groups. Multiple linear regression analysis was used to test the relationship between Chamberlain's line violation (CLV) and the clivus height ratio or atlanto-occipital LM height. Based on the degree of AOZ, the lateral masses in group B were classified as follows: segmentation, incomplete AOZ, complete AOZ. From groups A to C, there was a decreasing trend in the clivus height and clivus height ratio. There was a linear negative correlation between the clivus height ratio and CLV in the three groups. Generally, the atlanto-occipital LM height followed the order of group B < group C < group A. The atlanto-occipital LM height was included only in the equations of groups B. There were no cases of atlantoaxial dislocation (AAD) in group C. There was a decreasing trend in LM height from the segmentation type to the complete AOZ type in group B. BI can be divided into three categories: AOZ causes LM height loss; Clivus height loss; Both clivus and LM height loss. The clivus height ratio was found to play a decisive role in both controls and BI group, while the atlanto-occipital LM height loss caused by AOZ could be a secondary factor in patients with BI and AOZ. AOZ may be a necessary factor for AAD in patients with congenital BI. The degree of AOZ is associated with LM height in group B.


Asunto(s)
Articulación Atlantooccipital , Fosa Craneal Posterior , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Adolescente , Atlas Cervical/diagnóstico por imagen , Imagen por Resonancia Magnética , Anciano , Niño , Tomografía Computarizada por Rayos X
19.
Brain Struct Funct ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39192084

RESUMEN

The brain atlas is essential for exploring the anatomical structure and function of the brain. Non-human primates, such as cynomolgus macaque, have received increasing attention due to their genetic similarity to humans. However, current macaque brain atlases only offer coarse sections with intervals along the coronal direction, failing to meet the needs of single-cell resolution studies in functional and multi-omics research of the macaque brain. To address this issue, we utilized fluorescence micro-optical sectioning tomography to obtain sub-micron resolution cytoarchitectonic images of the macaque brain at the sagittal plane. Based on the obtained 8000 image sequences, a reference brain atlas comprising 45 sagittal sections was created, delineating 270 brain regions other than the cortex. Additionally, a website was established to share the reference atlas corresponding image data. This study is expected to provide an essential dataset and tool for scientists studying the macaque brain.

20.
Sci Total Environ ; 950: 175362, 2024 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-39117199

RESUMEN

Information about sea surface nitrate (SSN) concentrations is crucial for estimating oceanic new productivity and for carbon cycle studies. Due to the absence of optical properties in SSN and the intricate relationships with environmental factors affecting spatiotemporal dynamics, developing a more representative and widely applicable remote sensing inversion algorithm for SSN is challenging. Most methods for the remote estimation of SSN are based on data-driven neural networks or deep learning and lack mechanistic descriptions. Since fitting functions between the SSN and sea surface temperature (SST), mixed layer depth (MLD), and chlorophyll (Chl) content have been established for the open ocean, it is important to include the remote sensing indicator photosynthetically active radiation (PAR), which is critical in nitrate biogeochemical processes. In this study, we employed an algorithm for estimating the monthly average SSN on a global 1° by 1° resolution grid; this algorithm relies on the empirical relationship between the World Ocean Atlas 2018 (WOA18) monthly interpolated climatology of nitrate in each 1° × 1° grid and the estimated monthly SST and PAR datasets from Moderate Resolution Imaging Spectroradiometer (MODIS) and MLD from the Hybrid Coordinate Ocean Model (HYCOM). These results indicated that PAR potentially affects SSN. Furthermore, validation of the SSN model with measured nitrate data from different months and locations for the years 2018-2023 yielded a high prediction accuracy (N = 12,846, R2 = 0.93, root mean square difference (RMSE) = 3.12 µmol/L, and mean absolute error (MAE) = 2.22 µmol/L). Further independent validation and sensitivity tests demonstrated the validity of the algorithm for retrieving SSN.

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