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1.
J Med Cases ; 15(7): 126-129, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38993809

RESUMO

Renal cell carcinoma (RCC) is notorious for spreading to various organs, however, its occurrence in the gastrointestinal (GI) tract is uncommon and poses diagnostic challenges due to vague symptoms. Here, we present the case of a 64-year-old man experiencing recurrent RCC metastasis in the GI tract. He presented with multiple episodes of hematochezia and was found to have masses in the colon, liver, and peritoneum, with histopathology confirming RCC. The patient underwent systemic chemotherapy and palliative radiation therapy, leading to symptom relief. This case emphasizes the rarity of RCC metastasizing to the GI tract and the importance of timely recognition and frequent surveillance during the remission phase to detect recurrence.

2.
Eur Urol Open Sci ; 63: 81-88, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38572301

RESUMO

Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in "real-life" patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.

3.
BMC Genomics ; 24(1): 620, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37853316

RESUMO

BACKGROUND: Plants respond to stress through highly tuned regulatory networks. While prior works identified master regulators of iron deficiency responses in A. thaliana from whole-root data, identifying regulators that act at the cellular level is critical to a more comprehensive understanding of iron homeostasis. Within the root epidermis complex molecular mechanisms that facilitate iron reduction and uptake from the rhizosphere are known to be regulated by bHLH transcriptional regulators. However, many questions remain about the regulatory mechanisms that control these responses, and how they may integrate with developmental processes within the epidermis. Here, we use transcriptional profiling to gain insight into root epidermis-specific regulatory processes. RESULTS: Set comparisons of differentially expressed genes (DEGs) between whole root and epidermis transcript measurements identified differences in magnitude and timing of organ-level vs. epidermis-specific responses. Utilizing a unique sampling method combined with a mutual information metric across time-lagged and non-time-lagged windows, we identified relationships between clusters of functionally relevant differentially expressed genes suggesting that developmental regulatory processes may act upstream of well-known Fe-specific responses. By integrating static data (DNA motif information) with time-series transcriptomic data and employing machine learning approaches, specifically logistic regression models with LASSO, we also identified putative motifs that served as crucial features for predicting differentially expressed genes. Twenty-eight transcription factors (TFs) known to bind to these motifs were not differentially expressed, indicating that these TFs may be regulated post-transcriptionally or post-translationally. Notably, many of these TFs also play a role in root development and general stress response. CONCLUSIONS: This work uncovered key differences in -Fe response identified using whole root data vs. cell-specific root epidermal data. Machine learning approaches combined with additional static data identified putative regulators of -Fe response that would not have been identified solely through transcriptomic profiles and reveal how developmental and general stress responses within the epidermis may act upstream of more specialized -Fe responses for Fe uptake.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Deficiências de Ferro , Arabidopsis/genética , Modelos Logísticos , Raízes de Plantas/metabolismo , Ferro/metabolismo , Epiderme/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Arabidopsis/genética
4.
Plant Physiol ; 190(3): 2017-2032, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-35920794

RESUMO

Plants must tightly regulate iron (Fe) sensing, acquisition, transport, mobilization, and storage to ensure sufficient levels of this essential micronutrient. POPEYE (PYE) is an iron responsive transcription factor that positively regulates the iron deficiency response, while also repressing genes essential for maintaining iron homeostasis. However, little is known about how PYE plays such contradictory roles. Under iron-deficient conditions, pPYE:GFP accumulates in the root pericycle while pPYE:PYE-GFP is localized to the nucleus in all Arabidopsis (Arabidopsis thaliana) root cells, suggesting that PYE may have cell-specific dynamics and functions. Using scanning fluorescence correlation spectroscopy and cell-specific promoters, we found that PYE-GFP moves between different cells and that the tendency for movement corresponds with transcript abundance. While localization to the cortex, endodermis, and vasculature is required to manage changes in iron availability, vasculature and endodermis localization of PYE-GFP protein exacerbated pye-1 defects and elicited a host of transcriptional changes that are detrimental to iron mobilization. Our findings indicate that PYE acts as a positive regulator of iron deficiency response by regulating iron bioavailability differentially across cells, which may trigger iron uptake from the surrounding rhizosphere and impact root energy metabolism.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Deficiências de Ferro , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Arabidopsis/metabolismo , Ferro/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo
5.
Eur Phys J E Soft Matter ; 44(11): 135, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34779974

RESUMO

Patterns in drying droplets formed from colloidal solution of copper sulphate and gelatin are investigated with respect to variation of substrate hydrophobicity and salt concentration. Hydrophilic substrates as (i) glass, (ii) quartz and hydrophobic substrate as (iii) polypropylene (PP) have been used. It is observed that the dry residue pattern of salt crystals shows curved branches of crystalline aggregate growth about droplet centre for hydrophilic substrates, while thick, light and dark concentric bands of aggregates are observed for hydrophobic substrates. The geometry and topology of the patterns have been characterized through an analysis of fractal dimension and the topological measure, Euler characteristic. The fractal dimension of the deposit increases substantially with salt concentration for hydrophilic substrates, but decreases with concentration for hydrophobic substrate. Our analysis leads us to propose that an optimal viscosity contrast that facilitates prominent viscous fingers is a function of contact angle and salt concentration. We propose that substrate hydrophobicity and salt concentration together are responsible for DLA-like aggregation in evaporating droplets.

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