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Abstract Background Overall Survival (OS) and Progression-Free Interval (PFI) as survival times have been collected in The Cancer Genome Atlas (TCGA). It is of biomedical interest to consider their dependence in pathway detection and survival prediction. We intend to develop novel methods for integrating PFI as condition based on parametric survival models for identifying pathways associated with OS and predicting OS. Results Based on the framework of conditional probability, we developed a family of frailty-based parametric-models for this purpose, with exponential or Weibull distribution as baseline. We also considered two classes of existing methods with PFI as a covariate. We evaluated the performance of three approaches by analyzing RNA-seq expression data from TCGA for lung squamous cell carcinoma and lung adenocarcinoma (LUNG), brain lower grade glioma and glioblastoma multiforme (GBMLGG), as well as skin cutaneous melanoma (SKCM). Our focus was on fourteen general cancer-related pathways. The 10-fold cross-validation was employed for the evaluation of predictive accuracy. For LUNG, p53 signaling and cell cycle pathways were detected by all approaches. Furthermore, three approaches with the consideration of PFI demonstrated significantly better predictive performance compared to the approaches without the consideration of PFI. For GBMLGG, ten pathways (e.g., Wnt signaling, JAK-STAT signaling, ECM-receptor interaction, etc.) were detected by all approaches. Furthermore, three approaches with the consideration of PFI demonstrated better predictive performance compared to the approaches without the consideration of PFI. For SKCM, p53 signaling pathway was detected only by our Weibull-baseline-based model. And three approaches with the consideration of PFI demonstrated significantly better predictive performance compared to the approaches without the consideration of PFI. Conclusions Based on our study, it is necessary to incorporate PFI into the survival analysis of OS. Furthermore, PFI is a survival-type time, and improved results can be achieved by our conditional-probability-based approach.

Abstract Objective This study assesses the influence of hyperkalemia on both disease severity and the risk of mortality among patients admitted to the emergency room. Methods This retrospective observational study utilized data from the Chinese Emergency Triage Assessment and Treatment database (CETAT, version 2.0), which was designed to evaluate and optimize management strategies for emergency room (ER) patients. Patients were systematically categorized based on serum potassium levels. Relationships between serum potassium levels, risk of mortality, and the severity of illness were then analyzed using multifactorial logistic regression and through Receiver Operating Characteristic (ROC) analysis. The effectiveness of various treatments at lowering potassium levels was also investigated. Results 12,799 emergency patients were enrolled, of whom 20.1% (n = 2,577) were hypokalemic and 2.98% (n = 381) were hyperkalemic. Among hyperkalemic patients, the leading reasons for visiting the ER were altered consciousness 23.88% (n = 91), cardiovascular symptoms 22.31% (n = 85), and gastrointestinal symptoms 20.47% (n = 78). Comparative analysis with patients exhibiting normal potassium levels revealed hyperkalemia as an independent factor associated with mortality in the ER. Mortality risk appears to positively correlate with increasing potassium levels, reaching peaks when blood potassium levels ranged between 6.5 and 7.0. Hyperkalemia emerged as a strong predictor of death in the ER, with an Area Under the Curve (AUC) of 0.89. The most frequently prescribed treatment for hyperkalemia patients was diuretics (57.32%, n = 188), followed by intravenous sodium bicarbonate (50.91%, n = 167), IV calcium (37.2%, n = 122), insulin combined with high glucose (27.74%, n = 91), and Continuous Renal Replacement Therapy (CRRT) for 19.82% (n = 65). Among these, CRRT appeared to be the most efficacious at reducing potassium levels. Diuretics appeared relatively ineffective, while high-glucose insulin, sodium bicarbonate, and calcium preparations having no significant effect on the rate of potassium decline. Conclusion Hyperkalemia is common in emergency situations, especially among patients with altered consciousness. There is a strong positive correlation between the severity of hyperkalemia and mortality risk. CRRT appears to be the most effective potassium reducting strategy, while the use of diuretics should be approached with caution.

Environmental surveillance (ES) is a useful approach for monitoring circulating viruses, including polioviruses (PVs) and non-polio enteroviruses (NPEVs). In this study, the results of nine years of ES from 2013 to 2021 at six sampling sites in three cities in Fujian Province, China, were summarized. It showed that the sewage samples contained abundant viruses, but the positive rate was affected by different sampling sites. From the 520 samples, 431 PVs, 1,713 NPEVs, and 281 human adenoviruses (HAdVs) were isolated. PV isolates had been markedly affected following the adjustment of the immunization strategy. All but one PV isolate were Sabin-like strains without wild PVs. One isolate was vaccine-derived PV type 3 with 10 variation points in the VP1 region. After May 2016, PV type 2 was no longer detected, and PV type 3 became a superior serotype. Of 1,713 NPEVs, 24 serotypes were identified, including echovirus11 (E11), E6, coxsackievirus B3 (CVB3), CVB5, E7, and E3 were the predominant serotypes (37.65%, 20.96%, 11.50%, 8.87%, 8.23%, and 7.06%, respectively). The temporal dynamic of the six common serotypes was inconsistent. E3 was frequently isolated, but the number of isolates was low, with no obvious peaks. E6, E7, and CVB3 exhibited periodic changes with a high peak every three to four years, and E11 only had one high peak lasting four years. Summer-fall peaks of the echoviruses and spring-winter peaks of CVB were observed in the monthly distribution of virus isolation. The infectious isolates of various serotypes of different species identified from the sewage samples showed that ES is an essential part of pathogen surveillance.

Abstract In this paper, we take a numerical simulation of a complex moving rigid body under the impingement of a shock wave in three-dimensional space. Both compressible inviscid fluid and viscous fluid are considered with suitable boundary conditions. We develop a high order numerical boundary treatment for the complex moving geometries based on finite difference methods on fixed Cartesian meshes. The method is an extension of the inverse Lax-Wendroff (ILW) procedure in our works (Cheng et al., Appl Math Mech (Engl Ed) 42: 841–854, 2021; Liu et al.) for 2D problems. Different from the 2D case, the local coordinate rotation in 3D required in the ILW procedure is not unique. We give a theoretical analysis to show that the boundary treatment is independent of the choice of the rotation, ensuring the method is feasible and valid. Both translation and rotation of the body are taken into account in this paper. In particular, we reformulate the material derivative for inviscid fluid on the moving boundary with no-penetration condition, which plays a key role in the proposed algorithm. Numerical simulations on the cylinder and sphere are given, demonstrating the good performance of our numerical boundary treatments.

Myocardial infarction is one of the most severe heart diseases, leading to sudden death. Currently, angiography and stenting are widely performed in clinics, yet more effective treatment is still needed. Herein, we presented that dioscin, a natural product, showed protective effect on infarcted hearts via mitochondrial maintenance. Upon dioscin treatment, cardiac dysfunction was alleviated, and remodeling is prevented. Mechanistically, disocin maintains mitochondria function through the maintenance of Kreb's cycle, and suppresion of ROS accumulation. In this way, by targeting mitochondrial dysfunction, dioscin is a potential drug for infarcted hearts.

Purpose: Metastatic nasopharyngeal carcinoma (mNPC) remains incurable. This prospective study aimed to investigate whether adding cetuximab to cisplatin-based induction therapy could improve efficacy and survival for chemotherapy-naïve mNPC patients.Patients and Methods: Eligible chemotherapy-naïve mNPC patients were enrolled, including those initially diagnosed with mNPC (IM) and those with first-relapse metastases after radiotherapy (RM). Patients all received induction chemotherapy (IC) including docetaxel and cisplatin plus cetuximab. Those who obtained objective remission after IC would continue to receive radiotherapy concurrent with cetuximab and cisplatin, and further capecitabine as maintenance. Contemporaneous patients who received conventional therapy served as controls.Results: Forty-three patients were enrolled, including 17 IM and 26 RM patients. Thirty-nine (90.7%) patients had WHO III subtype. The overall response and complete response (CR) rates were, respectively, 79.1 and 34.9% after induction therapy and 76.7 and 46.5% after chemoradiotherapy. The 5-year overall survival (OS) and progression-free survival (PFS) rates reached 34.9 and 30%, respectively. Subgroup analysis showed that compared with RM patients, IM patients had a higher 5-year OS (58.8 vs. 19.2%) and PFS (52.9 vs. 19.2%). The IM group had a higher CR rate of induction treatment than the RM group (52.9 vs. 23.1%). No treatment-related death was observed. Twelve patients (27.9%) remained alive with disease-free survival times from 60+ to 135+ months. Control patients showed a substantially lower survival rate (5-year OS, 10.9%) and few long-term survivors.Conclusions: This regimen resulted in significantly improved efficacy and survival, which indicates a potentially curative role for chemotherapy-naïve mNPC, especially in newly diagnosed patients. A phase III clinical trial (NCT02633176) is ongoing for confirmation.

This study aimed to develop and validate a risk score for early prediction of venous thromboembolism (VTE) in patients with lung cancer. A total of 827 patients with lung cancer from February 2013 to February 2018 in our hospital were retrospectively analyzed. Demographic and clinicopathological variables independently correlated to VTE were applied to develop the risk score in the development group while examined in the validation group. The regression coefficients of multivariable logistic regression test were applied to assign a risk score system. The incidence of VTE was 12.3%, 12.7%, and 11.8% in all patients, in the development and validation groups, respectively. The 496 patients in the development group were classified into 3 groups: low risk (scores ≤3), moderate risk (scores 4-5), and high risk (scores ≥6). The risk of VTE was significantly and positively related to the risk scores in both development and validation groups. The risk score system aided proper stratification of patients with either high or low risk of VTE in the development and validation groups ( c statistic = 0.819 and 0.827, respectively). This risk score system based on the factors with most significant correlation showed good predictive ability and is potentially useful for predicting VTE in patients with lung cancer. However, it was developed and validated by a retrospective analysis and has significant limitations, and a prospective validation with all the classic variables assessing the thrombotic risk is needed for a solid conclusion.

Controversy continues on the tailored therapy for patients with larger renal cell carcinoma (RCC). We investigated whether partial nephrectomy (PN) can improve patient prognosis compared to radical nephrectomy (RN) and the indications for each approach in patients with T1b-2N0M0 RCC.A total of 9907 patients were identified from the Surveillance, Epidemiology, and End Results database from 2004 to 2012. Propensity scores were used to balance the selection bias of undergoing PN. Overall (OS) and cancer-specific survival (CSS) of patients undergoing PN and RN were compared. Cases were subdivided to investigate the advantages of each procedure.Overall, 1418 (14.3%) patients underwent PN. Before matching, PN led to better OS and CSS than RN in both Kaplan-Meier analysis and Cox regression (each p

Benzene, a known toxic, carcinogenic, and pervasively present environmental pollutant, necessitates effective monitoring strategies to assess human exposure. S-Phenylmercapturic acid (S-PMA) is a specific biomarker for benzene exposure. This study presents a point-of-care testing (POCT) assay for the detection of S-PMA in human urine, integrating salt-induced phase separation (SIPS) with surface-enhanced Raman spectroscopy (SERS). S-PMA in human urine was first effectively separated using SIPS and then detected using a portable Raman spectrometer employing Au colloids as the SERS substrate. The POCT assay exhibited a clear correlation between the signal intensity and logarithmic concentration of S-PMA (0-5 ppm), demonstrating satisfactory recovery and reproducibility. Moreover, high-throughput fingerprint identification and quantitative analysis of S-PMA in urine were achieved within 10 min, with a detection limit as low as 1.06 ppb, by performing SIPS-SERS on 96-well plates. This POCT method holds promise for personal exposure assessment and may potentially aid in the prevention of benzene-induced diseases. [ABSTRACT FROM AUTHOR]