Abstract
Laryngeal squamous cell carcinoma (LSCC) is a common tumor type. High recurrence rates remain an important factor affecting the survival and quality of life of advanced LSCC patients. We ...aimed to build a new nomogram and a random survival forest model using machine learning to predict the risk of LSCC progress. The study included 671 patients with AJCC stages III–IV LSCC. To develop a prognostic model, Cox regression analyses were used to assess the relationship between clinic-pathologic factors and disease-free survival (DFS). RSF analysis was also used to predict the DFS of LSCC patients. The ROC curve revealed that the Cox model exhibited good sensitivity and specificity in predicting DFS in the training and validation cohorts (1 year, validation AUC = 0.679, training AUC = 0.693; 3 years, validation AUC = 0.716, training AUC = 0.655; 5 years, validation AUC = 0.717, training AUC = 0.659). Random survival forest analysis showed that N stage, clinical stage, and postoperative chemoradiotherapy were prognostically significant variables associated with survival. The random forest model exhibited better prediction ability than the Cox regression model in the training cohort; however, the two models showed similar prediction ability in the validation cohort.
In recent years, head-mounted display technologies have greatly advanced. In order to overcome the accommodation-convergence conflict, light field displays reconstruct three-dimensional (3D) images ...with a focusing cue but sacrifice resolution. In this paper, a hybrid head-mounted display system that is based on a liquid crystal microlens array is proposed. By using a time-multiplexed method, the display signals can be divided into light field and two-dimensional (2D) modes to show comfortable 3D images with high resolution compensated by the 2D image. According to the experimental results, the prototype supports a 12.28 ppd resolution in the diagonal direction, which reaches 82% of the traditional virtual reality (VR) head-mounted display (HMD).
Abstract
Background and aims
Domestic violence (DV) are one of the important risk factors for women’s health outcomes. The aim of this study was explored the risk of DV association with the poor ...pregnancy outcomes (PPOs), including premature delivery, abortion, and stillbirth.
Methods
A nested case–control study was applied. Data from the Taiwan National Health Insurance Research Database were collected from 2000 to 2015. A total of 41,730 participants were included in this study, including 8,346 participants in the case group and 33,384 age- and index year-matched control group. Assessments of DA and PPOs were determined according to the International Classification of Diseases, 9th Revision. We conducted a conditional logistic regression analysis to estimate the effect of DV on PPOs.
Results
The mean age was 35.53 in the 41,730 female participants. The overall incidence rate of PPOs of the participants, who had experienced DV, was 84.05 per 100,000 person-years. which was significantly higher than that for the controls (18.19 per 100,000 person-years). The risk of PPOs was higher in the participants who had experienced DV than in the controls (adjusted odds ratio AOR = 3.31; 95% confidence interval CI 95% CI: 2.83–3.86), including for premature delivery (AOR = 3.57; 95% CI: 3.05–4.17), abortion (AOR = 3.31; 95% CI: 2.83–3.86) and stillbirth (AOR = 2.98; 95% CI: 2.55–3.47). The results showed that the longer a participant has been suffering DV, the risk of PPOs was higher.
Conclusions
Present results reaved the risk of PPOs associated with DV. Especially, the longer a woman has been experiencing DV, the risk of PPOs was higher, showed a dose–response effect.
The noradrenergic fibers of the locus coeruleus, together with mossy fibers and climbing fibers, comprise the three types of cerebellar afferents that modulate the cerebellar neuronal circuit. We ...previously demonstrated that noradrenaline (NA) modulated synaptic transmission in the mouse cerebellar cortex via adrenergic receptors (ARs). In the present study, we investigated the effect of NA on facial stimulation-evoked cerebellar molecular layer interneuron (MLI)-Purkinje cell (PC) synaptic transmission in urethane-anesthetized mice using an in vivo cell-attached recording technique and a pharmacological method. MLI-PC synaptic transmission was induced by air-puff stimulation (duration: 60 ms) of the ipsilateral whisker pad, which exhibited positive components (P1 and P2) accompanied by a pause in simple spike activity. Cerebellar molecular layer application of NA (15 µM) decreased the amplitude and area under the curve of P1, and the pause in simple spike activity, but increased the P2/P1 ratio. The NA-induced decrease in P1 amplitude was concentration-dependent, and the half-inhibitory concentration was 10.94 µM. The NA-induced depression of facial stimulation-evoked MLI-PC GABAergic synaptic transmission was completely abolished by blockade of α-ARs or α2-ARs, but not by antagonism of α1-ARs or β-ARs. Bath application of an α2-AR agonist inhibited MLI-PC synaptic transmission and attenuated the effect of NA on the synaptic response. NA-induced depression of MLI-PC synaptic transmission was completely blocked by a mixture of α2A- and 2B-AR antagonists, and was abolished by inhibition of protein kinase A. In addition, electrical stimulation of the molecular layer evoked MLI-PC GABAergic synaptic transmission in the presence of an AMPA receptor antagonist, which was inhibited by NA through α2-ARs. Our results indicate that NA inhibits MLI-PC GABAergic synaptic transmission by reducing GABA release via an α2-AR/PKA signaling pathway.
Hypoxia inducible factors (HIFs) are the key transcription factors that allow cancer cells to survive hypoxia. HIF's stability is mainly controlled by von Hippel–Lindau (pVHL)‐mediated ...ubiquitylation. Unlike sporadic clear‐cell renal carcinomas, VHL mutation is rarely observed in hepatocellular carcinoma (HCC) and the regulatory mechanisms of pVHL‐HIF signaling remain elusive. Here, it is shown that deubiquitylase ovarian tumor domain‐containing 6B (OTUD6B) suppresses HCC metastasis through inhibiting the HIF activity. OTUD6B directly interacts with pVHL, decreases its ubiquitylation and proteasomal degradation to reduce HIF‐1α accumulation in HCC cells under hypoxia. Surprisingly, OTUD6B limits the ubiquitylation of pVHL independent of its deubiquitylase activity. OTUD6B couples pVHL and elongin B/C to form more CBCVHL ligase complex, which protects pVHL from proteasomal degradation. Depletion of OTUD6B results in the dissociation of CBCVHL complex and the degradation of pVHL by Trp Asp repeat and suppressors of cytokine signaling box‐containing protein 1 (WSB1). In human HCC tissues, the protein level of OTUD6B is positively correlated with pVHL, but negatively with HIF‐1α and vascular endothelial growth factor. Low expression of OTUD6B predicts poor patient survival. Furthermore, OTUD6B gene is a direct transcriptional target of HIF‐1α and upregulated upon hypoxia. These results indicate a previously unrecognized feedback loop consisting of OTUD6B, pVHL, and HIF‐1α, and provide insights into the targeted hypoxic microenvironment for HCC therapy.
In this study, it is revealed that deubiquitylase ovarian tumor domain‐containing 6B (OTUD6B) couples von Hippel–Lindau (VHL) and elongin B/C to form more Cul2‐elongin B/C‐VHL ligase complex, which protects VHL protein from proteasomal degradation and represses the hypoxia inducible factor (HIF) pathway. Furthermore, OTUD6B is identified as a direct target of HIF‐1α and the negative feedback loop between OTUD6B and HIF‐1α regulates liver cancer metastasis under hypoxia.
This study introduces session-aware recommendation models, leveraging GRU (Gated Recurrent Unit) and attention mechanisms for advanced latent interaction data integration. A primary advancement is ...enhancing latent context, a critical factor for boosting recommendation accuracy. We address the existing models’ rigidity by dynamically blending short-term (most recent) and long-term (historical) preferences, moving beyond static period definitions. Our approaches, pre-combination (LCII-Pre) and post-combination (LCII-Post), with fixed (Fix) and flexible learning (LP) weight configurations, are thoroughly evaluated. We conducted extensive experiments to assess our models’ performance on public datasets such as Amazon and MovieLens 1M. Notably, on the MovieLens 1M dataset, LCII-PreFix achieved a 1.85% and 2.54% higher Recall@20 than II-RNN and BERT4Rec+st+TSA, respectively. On the Steam dataset, LCII-PostLP outperformed these models by 18.66% and 5.5%. Furthermore, on the Amazon dataset, LCII showed a 2.59% and 1.89% improvement in Recall@20 over II-RNN and CAII. These results affirm the significant enhancement our models bring to session-aware recommendation systems, showcasing their potential for both academic and practical applications in the field.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Linear ubiquitination catalyzed by HOIL-1-interacting protein (HOIP), the key component of the linear ubiquitination assembly complex, plays fundamental roles in tissue homeostasis by executing ...domain-specific regulatory functions. However, a proteome-wide analysis of the domain-specific interactome of HOIP across tissues is lacking. Here, we present a comprehensive mass spectrometry-based interactome profiling of four HOIP domains in nine mouse tissues. The interaction dataset provides a high-quality HOIP interactome resource with an average of approximately 90 interactors for each bait per tissue. HOIP tissue interactome presents a systematic understanding of linear ubiquitination functions in each tissue and also shows associations of tissue functions to genetic diseases. HOIP domain interactome characterizes a set of previously undefined linear ubiquitinated substrates and elucidates the cross-talk among HOIP domains in physiological and pathological processes. Moreover, we show that linear ubiquitination of Integrin-linked protein kinase (ILK) decreases focal adhesion formation and promotes the detachment of Shigella flexneri-infected cells. Meanwhile, Hoip deficiency decreases the linear ubiquitination of Smad ubiquitination regulatory factor 1 (SMURF1) and enhances its E3 activity, finally causing a reduced bone mass phenotype in mice. Overall, our work expands the knowledge of HOIP-interacting proteins and provides a platform for further discovery of linear ubiquitination functions in tissue homeostasis.
Improvement of methods for reliable and early diagnosis of the cellular diseases is necessary. A biological selectivity probe, such as an aptamer, is one of the candidate recognition layers that can ...be used to detect important biomolecules. Lung cancer is currently a typical cause of cancer-related deaths. In this work, an electrical sensing platform is built based on amine-terminated aptamer modified-gold electrodes for the specific, label-free detection of a human lung carcinoma cell line (A549). The microdevice, that includes a coplanar electrodes configuration and a simple microfluidic channel on a glass substrate, is fabricated using standard photolithography and cast molding techniques. A procedure of self-assembly onto the gold surface is proposed. Optical microscope observations and electrical impedance spectroscopy measurements confirm that the fabricated microchip can specifically and effectively identify A549 cells. In the experiments, the capacitance element that is dominant in the change of the impedance is calculated at the appropriate frequency for evaluation of the sensitivity of the biosensor. Therefore, a simple, inexpensive, biocompatible, and selective biosensor that has the potential to detect early-stage lung cancer would be developed.
Von Hippel-Lindau (VHL) is an important tumor suppressor, and its inactivation is a hallmark of inherited VHL disease and most sporadic clear cell renal cell carcinoma (ccRCC). VHL protein (pVHL) ...with missense point mutations are unstable and degraded by the proteasome because of the disruption of elongin binding. Deubiquitylase ovarian tumor domain-containing 6B (OTUD6B) had been documented to couple pVHL and elongin B to form stable VHL - elonginB - elonginC complex, which protects pVHL from degradation. However, whether OTUD6B governs the stability of pVHL wild type and the missense mutants in ccRCC remains largely elusive. Here, we reported that low OTUD6B level predicted poorer survival in ccRCC patients with VHL missense mutation, but not frameshift deletion and nonsense mutation. OTUD6B is able to interact with wild type pVHL and tumor-derived pVHL missense mutants, except for pVHL I151T, and decrease their ubiquitylation and proteasomal degradation in ccRCC cells. Functionally, we revealed that OTUD6B depletion enhanced cell migration and HIF-2α level in ccRCC cells in a pVHL dependent manner. In addition, OTUD6B depletion reduced the inhibitory effects of ectopic pVHL missense mutants on cell migration and HIF-2α level, except for pVHL I151T. Thus, we speculated that I151 residue might be one of key sites of pVHL binding to OTUD6B. These results suggested that OTUD6B is an important regulator for the stability of pVHL missense mutants, which provides a potential therapeutic strategy for ccRCC with VHL mutations.
In the era of Internet of Things, the demand for flexible and transparent electronic devices has shifted to the forefront of materials science research. However, the radiation damage to key ...performance of transparent devices under radiative environment remains as a critical issue. Here, we present a promising technology for nonvolatile transparent electronic devices based on flexible oxide heteroepitaxy. A direct fabrication of epitaxial lead lanthanum zirconate titanate on transparent flexible mica substrate with indium tin oxide electrodes is presented. The transparent flexible ferroelectric heterostructures not only retain their superior performance, thermal stability, reliability, and mechanical durability, but also exhibit remarkably robust properties against to a strong radiation exposure. Our study demonstrates an extraordinary concept to realize transparent flexible nonvolatile electronic devices for the design and development of next-generation smart devices with potential application in electronics, automotive, aerospace, and nuclear systems.
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