260 research outputs found

    Establishing a model predicting Gleason grade group upgrading in prostate cancer.

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    BACKGROUND: Gleason grade group (GG) upgrading is associated with increased biochemical recurrence (BCR), local progression, and decreased cancer-specific survival (CSS) in prostate cancer (PCa). However, descriptions of the risk factors of GG upgrading are scarce. The objective of this study was to identify risk factors and establish a model to predict GG upgrading. METHODS: There were 361 patients with PCa who underwent radical prostatectomy between May 2011 and February 2022 enrolled. Univariate and multivariate logistic regression analyses were identified and nomogram further narrowed down the contributing factors in GG upgrading. The correction curve and decision curve were used to assess the model. RESULTS: In the overall cohort, 141 patients had GG upgrading. But the subgroup cohort (GG ≤2) showed that 68 patients had GG upgrading. Multivariate logistic regression analysis showed that in the overall cohort, total prostate-specific antigen (tPSA) ≥10 ng/mL, systemic immune-inflammation index (SII) \u3e379.50, neutrophil-lymphocyte ratio (NLR) \u3e2.13, the GG of biopsy ≥3, the number of positive cores \u3e3 were independent risk factors in GG upgrading. In the cohort of biopsy GG ≤2, multivariate logistic regression showed that the tPSA ≥10 ng/mL, SII \u3e379.50 and the number of positive cores \u3e3 were independent risk factors in GG upgrading. A novel model predicting GG upgrading was established based on these three parameters. The area under the curve (AUC) of the prediction model was 0.759. The C-index of the nomogram was 0.768. The calibration curves of the model showed good predictive performance. Clinical decision curves indicated clinical benefit in the interval of 20% to 90% of threshold probability and good clinical utility. CONCLUSIONS: Combined levels of tPSA, SII and the positive biopsy cores distinguish patients with high-risk GG upgrading in the group of biopsy GG ≤2 and are helpful in the decision of treatment plans

    Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) patient with ARMC5 mutations.

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    BACKGROUND: Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a highly heterogeneous disease with divergent manifestations ranging from asymptomatic subclinical Cushing syndrome (CS) to overt Cushing syndrome with severe complications. ARMC5 mutations occur in 20 to 55% PBMAH patients usually with more severe phenotypes. Different ARMC5 mutations might be associated with diverse phenotypes of PBMAH. CASE PRESENTATION: A 39-year-old man was admitted to our hospital with progressive weight gain and severe hypertension. He presented typical CS and its classical metabolic and bone complications like hypertension and osteoporosis. The laboratory results showed high levels of cortisol and low levels of ACTH. Low- and high-dosed dexamethasone suppression tests were negative. Contrast-enhanced computed tomography (CT) revealed multiple bilateral irregular macronodular adrenal masses. Adrenal venous sampling (AVS) confirmed that the right adrenal gland with larger nodules secreted more hormone that the left side did. Right adrenalectomy and subsequent contralateral subtotal resection were conducted. His blood pressure and CS symptoms as well as comorbidities including backache and muscle weakness improved. Whole exome sequencing identified one ARMC5 germline mutation (c.1855C \u3e T, p. R619*), five ARMC5 somatic mutations (four novel mutations) in his right and left adrenal nodules. CONCLUSIONS: This PBMAH patient was identified with one ARMC5 germline mutation and five different somatic ARMC5 mutations (four novel mutations) in the different nodules of the bilateral adrenal masses. AVS combined with CT imagine could be helpful to determine the dominant side for adrenalectomy. Genetic testing is important for the diagnosis and management of the patient with PBMAH

    Heating of multi‐species upflowing ion beams observed by Cluster on March 28, 2001

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149495/1/epp320083.pd

    PHF8-GLUL axis in lipid deposition and tumor growth of clear cell renal cell carcinoma.

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    For clear cell renal cell carcinoma (ccRCC), lipid deposition plays important roles in the development, metastasis, and drug resistance. However, the molecular mechanisms underlying lipid deposition in ccRCC remain largely unknown. By conducting an unbiased CRISPR-Cas9 screening, we identified the epigenetic regulator plant homeodomain finger protein 8 (PHF8) as an important regulator in ccRCC lipid deposition. Moreover, PHF8 is regulated by von Hippel-Lindau (VHL)/hypoxia-inducible factor (HIF) axis and essential for VHL deficiency-induced lipid deposition. PHF8 transcriptionally up-regulates glutamate-ammonia ligase (GLUL), which promotes the lipid deposition and ccRCC progression. Mechanistically, by forming a complex with c-MYC, PHF8 up-regulates TEA domain transcription factor 1 (TEAD1) in a histone demethylation-dependent manner. Subsequently, TEAD1 up-regulates GLUL transcriptionally. Pharmacological inhibition of GLUL by l-methionine sulfoximine not only repressed ccRCC lipid deposition and tumor growth but also enhanced the anticancer effects of everolimus. Thus, the PHF8-GLUL axis represents a potential therapeutic target for ccRCC treatment

    Gene profiling and clinicopathological features for prognostic modeling of recurrence in non-metastatic clear-cell renal cell carcinoma.

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    BACKGROUND: Accurate risk stratification of renal cell carcinoma (RCC) is critical for selecting the most appropriate treatment options. Existing prognostic systems, which incorporate various clinical and pathological parameters, have limitations in terms of accuracy. However, it remains unclear whether integrating molecular data with clinicopathological features can enhance the identification of high-risk tumors. The objective of this study was to establish a model to predict RCC recurrence by integrating molecular data with clinicopathological features and to evaluate circulating tumor DNA (ctDNA) as a non-invasive prognostic marker. METHODS: Next-generation sequencing (NGS) was performed on 73 RCC patients, including 54 with clear-cell RCC (ccRCC). A prognostic model for disease-free survival (DFS) in non-metastatic ccRCC (NMCCRCC) was constructed and validated with two external datasets. The prognostic potential of ctDNA was assessed by its detection rates, mutation concordance with tumor tissue DNA, and association with clinical outcomes. RESULTS: Frequently altered genes in ccRCC included VHL (72.22%), PBRM1 (25.93%), BAP1 (20.37%), TP53 (11.11%), KDM5C (11.11%), and SETD2 (16.67%). Advanced T stage, BAP1, and SETD2 mutations were independent risk factors for recurrence in NMCCRCC patients. The model achieved a concordance index (C-index) of 0.833 and demonstrated area under the receiver operating characteristic (ROC) curve (AUC) values ranging from 0.900 to 0.821 for 1- to 5-year outcomes. In external validation, the model also demonstrated reliable performance in the external validation cohorts, with AUC values ranging from 0.688 to 0.751 and 0.721 to 0.768, respectively. The mutation concordance between ctDNA and tumor tissue DNA was 61.54%, with higher ctDNA detection rates observed in patients with distant metastasis. CONCLUSIONS: Our prognostic model, factoring in T stage and genetic mutations in BAP1 and SETD2, effectively predicted recurrence in NMCCRCC patients. The potential of ctDNA as a non-invasive prognostic biomarker was underscored by its high detection rates and mutation concordance

    Detection of magnetospheric ion drift patterns at Mars

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    Mars lacks a global magnetic field, and instead possesses small-scale crustal magnetic fields, making its magnetic environment fundamentally different from intrinsic magnetospheres like those of Earth or Saturn. Here we report the discovery of magnetospheric ion drift patterns, typical of intrinsic magnetospheres, at Mars usingmeasurements fromMarsAtmosphere and Volatile EvolutioNmission. Specifically, we observewedge-like dispersion structures of hydrogen ions exhibiting butterfly-shaped distributions within the Martian crustal fields, a feature previously observed only in planetary-scale intrinsic magnetospheres. These dispersed structures are the results of driftmotions that fundamentally resemble those observed in intrinsic magnetospheres. Our findings indicate that the Martian magnetosphere embodies an intermediate case where both the unmagnetized and magnetized ion behaviors could be observed because of the wide range of strengths and spatial scales of the crustal magnetic fields around Mars.Comment: 10 pages, 6 figure

    Evidence for lunar tide effects in Earth’s plasmasphere

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    Tides are universal and affect spatially distributed systems, ranging from planetary to galactic scales. In the Earth–Moon system, effects caused by lunar tides were reported in the Earth’s crust, oceans, neutral gas-dominated atmosphere (including the ionosphere) and near-ground geomagnetic field. However, whether a lunar tide effect exists in the plasma-dominated regions has not been explored yet. Here we show evidence of a lunar tide-induced signal in the plasmasphere, the inner region of the magnetosphere, which is filled with cold plasma. We obtain these results by analysing variations in the plasmasphere’s boundary location over the past four decades from multisatellite observations. The signal possesses distinct diurnal (and monthly) periodicities, which are different from the semidiurnal (and semimonthly) variations dominant in the previously observed lunar tide effects in other regions. These results demonstrate the importance of lunar tidal effects in plasma-dominated regions, influencing understanding of the coupling between the Moon, atmosphere and magnetosphere system through gravity and electromagnetic forces. Furthermore, these findings may have implications for tidal interactions in other two-body celestial systems

    Sciences for The 2.5-meter Wide Field Survey Telescope (WFST)

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    The Wide Field Survey Telescope (WFST) is a dedicated photometric survey facility under construction jointly by the University of Science and Technology of China and Purple Mountain Observatory. It is equipped with a primary mirror of 2.5m in diameter, an active optical system, and a mosaic CCD camera of 0.73 Gpix on the main focus plane to achieve high-quality imaging over a field of view of 6.5 square degrees. The installation of WFST in the Lenghu observing site is planned to happen in the summer of 2023, and the operation is scheduled to commence within three months afterward. WFST will scan the northern sky in four optical bands (u, g, r, and i) at cadences from hourly/daily to semi-weekly in the deep high-cadence survey (DHS) and the wide field survey (WFS) programs, respectively. WFS reaches a depth of 22.27, 23.32, 22.84, and 22.31 in AB magnitudes in a nominal 30-second exposure in the four bands during a photometric night, respectively, enabling us to search tremendous amount of transients in the low-z universe and systematically investigate the variability of Galactic and extragalactic objects. Intranight 90s exposures as deep as 23 and 24 mag in u and g bands via DHS provide a unique opportunity to facilitate explorations of energetic transients in demand for high sensitivity, including the electromagnetic counterparts of gravitational-wave events detected by the second/third-generation GW detectors, supernovae within a few hours of their explosions, tidal disruption events and luminous fast optical transients even beyond a redshift of 1. Meanwhile, the final 6-year co-added images, anticipated to reach g about 25.5 mag in WFS or even deeper by 1.5 mag in DHS, will be of significant value to general Galactic and extragalactic sciences. The highly uniform legacy surveys of WFST will also serve as an indispensable complement to those of LSST which monitors the southern sky.Comment: 46 pages, submitted to SCMP

    A Robust Point-Matching Algorithm for Remote Sensing Image Registration

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