Traditional radiomics models mainly rely on explicitly-designed handcrafted features from medical images. This paper aimed to investigate if deep features extracted via transfer learning can generate ...radiomics signatures for prediction of overall survival (OS) in patients with Glioblastoma Multiforme (GBM). This study comprised a discovery data set of 75 patients and an independent validation data set of 37 patients. A total of 1403 handcrafted features and 98304 deep features were extracted from preoperative multi-modality MR images. After feature selection, a six-deep-feature signature was constructed by using the least absolute shrinkage and selection operator (LASSO) Cox regression model. A radiomics nomogram was further presented by combining the signature and clinical risk factors such as age and Karnofsky Performance Score. Compared with traditional risk factors, the proposed signature achieved better performance for prediction of OS (C-index = 0.710, 95% CI: 0.588, 0.932) and significant stratification of patients into prognostically distinct groups (P < 0.001, HR = 5.128, 95% CI: 2.029, 12.960). The combined model achieved improved predictive performance (C-index = 0.739). Our study demonstrates that transfer learning-based deep features are able to generate prognostic imaging signature for OS prediction and patient stratification for GBM, indicating the potential of deep imaging feature-based biomarker in preoperative care of GBM patients.
The Weishancheng area of Tongbai County, Henan Province, is an important Au‐Ag polymetallic ore concentration area in China, characterized by a widespread distribution of plutons and frequent ...magmatic activities. To investigate the genetic relationship between magmatism and the mineralization of gold and silver polymetallic deposits in the area, this study focuses on the porphyritic monzogranite of the Liangwan pluton and the biotite granite of the Taoyuan pluton in detail. The zircon U‐Pb age of the Liangwan pluton is 128.5 ± 0.7 Ma, placing its intrusion age in the Early Cretaceous. Similarly, the zircon U‐Pb age of the Taoyuan pluton is 431.3 ± 2.7 Ma, indicating an intrusion age in the Early Silurian. Petrogeochemical analysis reveals that both the Liangwan and Taoyuan plutons exhibit high SiO2, Na2O and Al2O3 contents, along with low MgO, Fe2O3 and CaO contents, indicating a (high‐K) calc‐alkaline series, and have the properties of peraluminous I‐type granite. The total rare earth elements (REE) concentrations are low, with noticeable fractionation between light and heavy REE, and a negative Eu anomaly. High‐field‐strength elements (such as Nb, Ta, P, Ti) are depleted, while the large‐ion lithophile elements (such as Rb, K, Pb) are enriched. The εHf(t) values of the Liangwan and Taoyuan plutons range from −16.1 to −18.8 and from 11.0 to 14.6, respectively. The mean values of Hf two‐stage model ages (TDM2) are 603 Ma and 2230 Ma, respectively. These results suggest that the Liangwan pluton may have formed through partial melting of ancient crustal materials in the Palaeoproterozoic, during extensional tectonic events following the subduction of Izanagi Plate. It appears closely linked to Au‐Ag mineralization in the ore concentration area. The Taoyuan pluton likely originated from the depleted mantle and experienced some degree of crustal contamination. However, it is unrelated to regional mineralization.
The formation of the Liangwan granitic pluton in Weishancheng ore concentration area may be linked to the subduction of the Izanagi Plate towards the Eurasian Plate margin during the Early Cretaceous, the resulting upwelling of the asthenosphere led to the remelting of the overlying crust, which regionally correlates with the mineralization of the Poshan silver deposit. In contrast, the Taoyuan granitic pluton was formed through the partial melting of the Erlangping subarc crust under hydrothermal transformation during the Early Silurian, with no direct relationship with gold and silver mineralization in the region.
Riociguat, a soluble guanylate cyclase stimulator, has been shown in a phase 2 trial to be beneficial in the treatment of pulmonary arterial hypertension.
In this phase 3, double-blind study, we ...randomly assigned 443 patients with symptomatic pulmonary arterial hypertension to receive placebo, riociguat in individually adjusted doses of up to 2.5 mg three times daily (2.5 mg-maximum group), or riociguat in individually adjusted doses that were capped at 1.5 mg three times daily (1.5 mg-maximum group). The 1.5 mg-maximum group was included for exploratory purposes, and the data from that group were analyzed descriptively. Patients who were receiving no other treatment for pulmonary arterial hypertension and patients who were receiving endothelin-receptor antagonists or (nonintravenous) prostanoids were eligible. The primary end point was the change from baseline to the end of week 12 in the distance walked in 6 minutes. Secondary end points included the change in pulmonary vascular resistance, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class, time to clinical worsening, score on the Borg dyspnea scale, quality-of-life variables, and safety.
By week 12, the 6-minute walk distance had increased by a mean of 30 m in the 2.5 mg-maximum group and had decreased by a mean of 6 m in the placebo group (least-squares mean difference, 36 m; 95% confidence interval, 20 to 52; P<0.001). Prespecified subgroup analyses showed that riociguat improved the 6-minute walk distance both in patients who were receiving no other treatment for the disease and in those who were receiving endothelin-receptor antagonists or prostanoids. There were significant improvements in pulmonary vascular resistance (P<0.001), NT-proBNP levels (P<0.001), WHO functional class (P=0.003), time to clinical worsening (P=0.005), and Borg dyspnea score (P=0.002). The most common serious adverse event in the placebo group and the 2.5 mg-maximum group was syncope (4% and 1%, respectively).
Riociguat significantly improved exercise capacity and secondary efficacy end points in patients with pulmonary arterial hypertension. (Funded by Bayer HealthCare; PATENT-1 and PATENT-2 ClinicalTrials.gov numbers, NCT00810693 and NCT00863681, respectively.).
A convergent and highly stereoselective 4+2 cycloaddition of in situ‐generated ortho‐Quinone methides (o‐QMs) and azlactone enols has been successfully developed through a triple Brønsted acid ...catalysis strategy. This protocol provides an efficient and mild access to various densely functionalized dihydrocoumarins bearing adjacent quaternary and tertiary stereogenic centers in high yields with excellent diastereo‐ and enantioselectivity.
Triple activation! A convergent and highly stereoselective 4+2 cycloaddition of in situ generated ortho‐Quinone methides (o‐QMs) and azlactone enols has been successfully developed through a triple Brønsted acid catalysis strategy. This protocol provides an efficient and mild access to various densely functionalized dihydrocoumarins (see scheme).
A global view of pulmonary hypertension Hoeper, Marius M; Humbert, Marc; Souza, Rogerio ...
The lancet respiratory medicine,
04/2016, Letnik:
4, Številka:
4
Journal Article
Recenzirano
Pulmonary hypertension is a substantial global health issue. All age groups are affected with rapidly growing importance in elderly people, particularly in countries with ageing populations. Present ...estimates suggest a pulmonary hypertension prevalence of about 1% of the global population, which increases up to 10% in individuals aged more than 65 years. In almost all parts of the world, left-sided heart and lung diseases have become the most frequent causes of pulmonary hypertension. About 80% of affected patients live in developing countries, where pulmonary hypertension is frequently associated with congenital heart disease and various infectious disorders, including schistosomiasis, HIV, and rheumatic heart disease. These forms of pulmonary hypertension occur predominantly in those younger than 65 years. Independently of the underlying disease, the development of pulmonary hypertension is associated with clinical deterioration and a substantially increased mortality risk. Global research efforts are needed to establish preventive strategies and treatments for the various types of pulmonary hypertension.
Abstract
Background
Due to post-cleavage residence of the Cas9-sgRNA complex at its target, Cas9-induced DNA double-strand breaks (DSBs) have to be exposed to engage DSB repair pathways. Target ...interaction of Cas9-sgRNA determines its target binding affinity and modulates its post-cleavage target residence duration and exposure of Cas9-induced DSBs. This exposure, via different mechanisms, may initiate variable DNA damage responses, influencing DSB repair pathway choices and contributing to mutational heterogeneity in genome editing. However, this regulation of DSB repair pathway choices is poorly understood.
Results
In repair of Cas9-induced DSBs, repair pathway choices vary widely at different target sites and classical nonhomologous end joining (c-NHEJ) is not even engaged at some sites. In mouse embryonic stem cells, weakening the target interaction of Cas9-sgRNA promotes bias towards c-NHEJ and increases target dissociation and reduces target residence of Cas9-sgRNAs in vitro. As an important strategy for enhancing homology-directed repair, inactivation of c-NHEJ aggravates off-target activities of Cas9-sgRNA due to its weak interaction with off-target sites. By dislodging Cas9-sgRNA from its cleaved targets, DNA replication alters DSB end configurations and suppresses c-NHEJ in favor of other repair pathways, whereas transcription has little effect on c-NHEJ engagement. Dissociation of Cas9-sgRNA from its cleaved target by DNA replication may generate three-ended DSBs, resulting in palindromic fusion of sister chromatids, a potential source for CRISPR/Cas9-induced on-target chromosomal rearrangements.
Conclusions
Target residence of Cas9-sgRNA modulates DSB repair pathway choices likely through varying dissociation of Cas9-sgRNA from cleaved DNA, thus widening on-target and off-target mutational spectra in CRISPR/Cas9 genome editing.
Optoelectronic synapses integrating synaptic and optical-sensing functions exhibit large advantages in neuromorphic computing for visual information processing and complex learning, recognition, and ...memory in an energy-efficient way. However, electric stimulation is still essential for existing optoelectronic synapses to realize bidirectional weight-updating, restricting the processing speed, bandwidth, and integration density of the devices. Herein, a two-terminal optical synapse based on a wafer-scale pyrenyl graphdiyne/graphene/PbS quantum dot heterostructure is proposed that can emulate both the excitatory and inhibitory synaptic behaviors in an optical pathway. The simple device architecture and low-dimensional features of the heterostructure endow the optical synapse with robust flexibility for wearable electronics. This optical synapse features a linear and symmetric conductance-update trajectory with numerous conductance states and low noise, which facilitates the demonstration of accurate and effective pattern recognition with a strong fault-tolerant capability even at bending states. A series of logic functions and associative learning capabilities have been demonstrated by the optical synapses in optical pathways, significantly enhancing the information processing capability for neuromorphic computing. Moreover, an integrated visible information sensing memory processing system based on the optical synapse array is constructed to perform real-time detection, in situ image memorization, and distinction tasks. This work is an important step toward the development of optogenetics-inspired neuromorphic computing and adaptive parallel processing networks for wearable electronics.
Graphdiyne (GDY) is emerging as a promising material for various applications owing to its unique structure and fascinating properties. However, the application of GDY in electronics and ...optoelectronics are still in its infancy, primarily owing to the huge challenge in the synthesis of large-area and uniform GDY film for scalable applications. Here a modified van der Waals epitaxy strategy is proposed to synthesize wafer-scale GDY film with high uniformity and controllable thickness directly on graphene (Gr) surface, providing an ideal platform to construct large-scale GDY/Gr-based optoelectronic synapse array. Essential synaptic behaviors have been realized, and the linear and symmetric conductance-update characteristics facilitate the implementation of neuromorphic computing for image recognition with high accuracy and strong fault tolerance. Logic functions including “NAND” and “NOR” are integrated into the synapse which can be executed in an optical pathway. Moreover, a visible information sensing-memory-processing system is constructed to execute real-time image acquisition,
in situ
image memorization and distinction tasks, avoiding the time latency and energy consumption caused by data conversion and transmission in conventional visual systems. These results highlight the potential of GDY in applications of neuromorphic computing and artificial visual systems.
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