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Abstract Background Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. Methods Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. Discussion The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. Trial registration anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Abstract Background Nanotechnology has demonstrated its vital significance in all aspects of daily life. Our research was conducted to estimate the potential of primed seed with chitosan nanoparticles in seed growth and yield by inducing plant secondary metabolism of Pancratium maritimum L. one of the important medicinal plants. Petri dish and pot experiments were carried out. Seeds of Pancratium maritimum L. were soaked in Nano solution (0.1, 0.5, 1 mg/ ml) for 4, 8, 12 h. Germination parameters (germination percentage, germination velocity, speed of germination, germination energy, germination index, mean germination time, seedling shoot and root length, shoot root ratio, seedling vigor index, plant biomass and water content), alkaloids and antioxidant activity of Pancratium maritimum L. were recorded and compared between coated and uncoated seeds. Results Our results exhibited that chitosan nanopriming had a positive effect on some growth parameters, while it fluctuated on others. However, the data showed that most germination parameters were significantly affected in coated seeds compared to uncoated seeds. GC-MS analysis of Pancratium maritimum L. with different nanopriming treatments showed that the quantity of alkaloids decreased, but the amount of pancratistatin, lycorine and antioxidant content increased compared with the control. Conclusions Applying chitosan nanoparticles in priming seeds might be a simple and effective way to improve the quantity of secondary metabolites of Pancratium maritimum L. valuable medicinal plant.

Background: Traditional tumor markers such as cancer antigen 15.3 (CA15.3) and carcinoembryonic antigen (CEA) exhibit limited clinical utility in breast cancer due to their lack of sensitivity and specificity, particularly for detecting low-volume tumors. Other serum markers, such as nestin, may offer more promise. This study aimed to assess the clinical significance of serum nestin and CA15.3 in breast cancer patients.Method: This case-control study enrolled 80 normal control females and 80 females with breast cancer. Serum samples were collected from both control and breast cancer groups. The serum nestin and CA15.3 levels were measured in all samples using enzyme-linked immunosorbent assay (ELISA) kits.Results: The serum levels of nestin and CA15.3 were found to be significantly elevated in the breast cancer patient group compared with the control group. Preoperative serum nestin levels exceeding 9.9 ng/ml demonstrated a substantial odds ratio of 27 (confidence interval: 4.57-159.67; P = 0.0003). In receiver operating characteristic curve analysis, serum nestin exhibited the highest significant area under the curve at 85.2% (P < 0.001), followed by serum CA15.3 at 70% (P = 0.021). Post-surgery serum nestin levels significantly decreased compared with pre-surgery levels (P = 0.045).Conclusion: Serum nestin outperforms serum CA15.3 in diagnosing breast cancer patients. Elevated serum nestin levels may represent a significant risk factor for the development of breast cancer. Furthermore, serum nestin can monitor the effects of surgery, whereas none of the assessed biomarkers exhibit a significant role in monitoring the effects of chemotherapy on breast cancer patients.

Abstract The crude extract of Hemimycale sp. marine sponge was evaluated as a cytotoxic drug against different cell lines; whereas it exhibited promising selective activity toward the breast cancer cell line only with IC50 value 199.6 ± 0.00512 µg/ml. Moreover, its cytotoxic activity against the breast cancer cell line was reevaluated upon forming total extract-loaded niosomes. This revealed an IC50 value of 44.35 ± 0.011128 µg/ml, indicating the potential contribution of niosomes in boosting cell penetration and activity as a result. Owing to highlight the bioactive constituents responsible for the cytotoxic activity, metabolomics profiling of Hemimycale sp. was performed using liquid chromatography coupled with high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS) revealing tentative identification of phytoconstituents clusters like as, diterpenes, sesterterpenes and sterols. Additionally, the cytotoxic activity of the crude extract was explained on the molecular level, whereas the dereplicated compounds were evaluated in silico against the Epidermal Growth Factor Receptor tyrosine kinase (EGFR). The sesterterpenoid derivatives phorbaketal A acetate (12) and secoepoxy ansellone A (13) together with mycalol-522 (17) showed the best binding energy.

Real-time localization is a crucial task in various applications, such as automatic vehicles (AV), robotics, and smart city. This study proposes a framework for map-aided LiDAR-inertial localization, with the objective of accurately estimating the trajectory in a point clouds map. The proposed framework addresses the localization problem through a factor graph optimization (FGO), enabling the fusion of homogenous measurements for sensor fusion and designed absolute and relative constraints. Specifically, the framework estimates the light detection and ranging (LiDAR) odometry by leveraging inertial measurement unit (IMU) and registering corresponding featured points. To eliminate the accumulative error, this paper employs a ground plane distance and a map matching error to constraint the positioning error along the trajectory. Finally, local odometry and constraints are integrated using a FGO, including LiDAR odometry, IMU pre-integration, and ground constraints, map matching constraints, and loop closure. Experimental results were evaluated on an open-source dataset, UrbanNav, with an overall localization accuracy of 2.29 m (root mean square error, RMSE).

The coexistence of mixed numerologies with OFDM introduces significant inter-numerology interference (INI) due to high out-of-band emission (OOBE). This interference worsens with increasing offset between numerologies, negatively impacting system performance. To address this issue, this paper proposes the use of a Hybrid Waveforms (HW) technique to mitigate the effects of INI in mixed-numerology systems. Specifically, f-OFDM, UFMC, and WOLA waveforms are employed instead of OFDM to suppress OOBE for users with higher numerology. The effectiveness of the proposed technique is evaluated using the Vienna 5G link-level simulator. Simulation results demonstrate that utilizing f-OFDM, UFMC, and WOLA waveforms for higher numerology users is more efficient in reducing INI compared to OFDM. By implementing the proposed framework, user throughput increases and Bit Error Rate (BER) decreases. Among the hybrid waveforms, f-OFDM proves to be the most effective, providing the highest throughput and the lowest BER when compared to UFMC, WOLA, and OFDM. For instance, in the case of f-OFDM, when the power of the second user is ten times that of the first user, the user BER in the uplink can be reduced by 63.3%, and its throughput can be increased by 47.3%. Similarly, in the downlink, the user BER can be reduced by 60.9%, and its throughput can be increased by 43%. These improvements are observed when comparing against the traditional system (OFDM), where the first user uses a subcarrier spacing of 15 kHz and the second user uses a 60 kHz spacing with a 180 kHz guard band.

Abstract Background A missed abortion is a spontaneous abortion in which the embryo or fetus has already died but has remained in the uterus for days or weeks with a closed cervical ostium. Termination of pregnancy could be achieved either by surgical evacuation or medical or expectant management. Letrozole is a third-generation aromatase inhibitor. According to many recent studies, letrozole given for three days before the administration of misoprostol was more effective than misoprostol alone at inducing abortion. Our study compared the efficacy of various letrozole regimens (10 mg/d for three days and a single dose of 20 mg) combined with misoprostol vs. misoprostol alone in inducing abortion. To find the most efficient regimen of letrozole administered before misoprostol to induce an abortion. Methodology This prospective, parallel, three-arm, single-blinded, allocation-concealed randomized controlled trial was conducted in Sohag Teaching Hospital in Upper Egypt. We randomly divided 105 patients with anembryonic missed abortion (up to 63 days gestation) with no history of medical disorders or a history of allergies to misoprostol or letrozole into three equal groups (a single-dose letrozole group, a multiple-dose letrozole group, and a misoprostol-only group). The complete abortion rate, incomplete abortion rate, failure to abort rate, and induction-to-abortion interval were all collected. All statistical calculations were performed using the computer program SPSS (Statistical Package for the Social Science, SPSS Inc., Chicago, IL, USA). Results The complete abortion rate was significantly higher in the single-dose letrozole and multiple-dose letrozole groups than in the misoprostol group (p values = 0.0455 and 0.001, respectively). On the other hand, there was no significant difference in the complete abortion rate between the single-dose group and the multiple-dose letrozole group (p-value = 0.1713). The time to complete abortion was significantly shorter in the single-dose and multiple-dose letrozole groups than in the misoprostol group (p values = 0.0036 and 0.0049, respectively). On the other hand, there was no significant difference in the time to complete abortion between the single-dose letrozole group and the multiple-dose letrozole group (P = 0.532). Conclusion Single- and multiple-dose letrozole regimens followed by misoprostol had a higher rate and a shorter time to complete abortion than misoprostol alone. Trial registration The trial is registered at gov with the name “letrozole and abortion” and the identifier “NCT05198050”. The date of registration was April 1, 2022, registered prospectively. URL: https://register.clinicaltrials.gov/prs/app/action/ViewOrUnrelease?uid=U0004GED&ts=25&sid=S000BPDQ&cx=43mobl .

PurposeIn this cohort study, 5-year data from the Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry (ie, CONFIRM) were examined to identify associations of baseline aspirin and statin use with mortality, major adverse cardiovascular events (MACE), and myocardial infarction (MI) in individuals without substantial (≥50%) stenosis.Materials and methodsIn this prospective cohort study, all participants in the registry underwent coronary CT angiography and were classified as having no detectable coronary plaque or having nonobstructive coronary artery disease (CAD) (1%-49% stenosis). Participants with obstructive (≥50%) stenosis were excluded from analysis. The study commenced in June 2003 and was completed in March 2016. All unadjusted and risk-adjusted analyses utilized the Cox proportional hazard model with hospital sites modeled using shared frailty.ResultsA total of 6386 participants with no detectable plaque or with nonobstructive CAD were included (mean age, 56.0 years ± 13.3 [SD], 52% men). The mean follow-up period was 5.66 years ± 1.10. Nonobstructive CAD (n = 2815, 44% of all participants included in the study) was associated with a greater risk of all-cause mortality (10.6% [298 of 2815] vs 4.8% [170 of 3571], P < .001) compared to those without CAD (n = 3571, 56%). Baseline aspirin and statin use was documented for 1415 and 1429 participants, respectively, with nonobstructive CAD, and for 1560 and 1565 participants without detectable plaque, respectively. In individuals with nonobstructive CAD, baseline aspirin use was not associated with a reduction in MACE (10.9% [102 of 936] vs 14.7% [52 of 355], P = .06), all-cause mortality (9.6% [95 of 991] vs 10.9% [46 of 424], P = .468), or MI (4.4% [41 of 936] vs 6.2% [22 of 355], P = .18). On multivariate risk-adjusted analysis, baseline statin use was associated with a lower rate of MACE (hazard ratio, 0.59; 95% CI: 0.40, 0.87; P = .007). Neither therapy improved clinical outcomes for participants with no detectable plaque.ConclusionIn participants with nonobstructive CAD, baseline use of statins, but not of aspirin, was associated with improved clinical outcomes. Neither therapy was associated with benefit in participants without plaque.Keywords: Aspirin, Statin, Coronary Artery Disease, CT Angiography, Nonobstructive Coronary Artery DiseaseClinical trial registration no. NCT01443637 Supplemental material is available for this article. © RSNA, 2022See also the commentary by Canan and Navar in this issue.

ABSTRACTHepatocellular carcinoma (HCC) has been linked to the gut microbiota, with recent studies revealing the potential of gut-generated responses to influence several arms of the immune responses relevant to HCC formation. The pro- or anti-tumor effects of specific bacterial strains or gut microbiota-related metabolites, such as bile acids and short-chain fatty acids, have been highlighted in many human and animal studies. The critical role of the gut microbiota in HCC development has spurred interest in modulating the gut microbiota through dietary interventions, probiotics, and fecal microbiota transplantation as a potential strategy to improve liver cancer outcomes. Encouragingly, preclinical and clinical studies have demonstrated that modulation of the gut microbiota can ameliorate liver function, reduce inflammation, and inhibit liver tumor growth, underscoring the potential of this approach to improve HCC outcomes. As research continues to unravel the complex and dynamic mechanisms underlying the gut-liver axis, the development of safe and effective interventions to target this pathway for liver cancer prevention and treatment appears to be on the horizon, heralding a significant advance in our ongoing efforts to combat this devastating disease.

A novel technique is proposed for finding an approximate solution of the strongly nonlinear ordinary differential equation for the charged damped pendulum with one degree of freedom. The method relies on a transformation of the governing nonlinear differential equation that keeps unchanged the order of the highest derivative, in conjunction with a modified homotopy perturbation technique (MHPM). Only quadratic damping is considered for the numerical computations. To validate the used technique, the obtained results are compared to those arising from a numerical solution by Runge–Kutta of the fourth order (RK4) and by finite differences (FD). Good agreement between the two solutions is reached when quadratic damping is suppressed. In the presence of damping, agreement takes place only for a rather limited range of times. Plots of the analytical solutions are provided for both cases. The proposed method may be used to analyze a wide class of nonlinear differential equations.

Abstract Background Fear of falling is associated with numerous negative health outcomes in older adults and can limit the rehabilitation process. Hypnosis is now recognized as an effective treatment for a variety of conditions, especially anxiety and pain, which can be integrated safely with conventional medicine. The objective of this study was to assess the feasibility and acceptability of a hypnosis intervention in hospitalized older adults to reduce fear of falling. Methods In this feasibility randomized controlled trial, 32 older patients, hospitalized in geriatric rehabilitation wards, were randomly allocated (1:1 ratio) to either an intervention group (hypnosis, 2 sessions, one per week, plus usual rehabilitation program) or a control group (usual rehabilitation program only). Clinical assessors and statistician were blinded to group allocation. Primary outcomes were recruitment rate, retention rate, and adherence to the intervention. Exploratory outcomes, analyzed according to the intention-to-treat principle, included impact of hypnosis on fear of falling (assessed by a new scale perform-FES), functional status, in-hospital falls, and length of hospital stay. Results Recruitment rate was 1.3 patients per week. The recruitment of the population sample was achieved in 5.5 months. The retention rate did not differ significantly between groups and a good adherence to the hypnosis intervention was achieved (77% of patients received the full intervention). No adverse event related to the hypnosis intervention was observed. Regarding exploratory clinical outcomes, no differences were found between groups on any outcome. Conclusion Hypnosis is feasible and well accepted in a geriatric hospitalized population undergoing rehabilitation. Further pilot work should be conducted, with an increased number of hypnosis sessions, before conducting a full-scale trial to conclude whether, or not, hypnosis is effective to reduce fear of falling. Trial registration NCT04726774.

(1) Background: Geriatric patients are at high risk of complications of Coronavirus disease-2019 (COVID-19) and are good candidates for antiviral drugs. (2) Methods: A retrospective study of electronic health records (EHRs) aiming to describe antiviral (nirmatrelvir and ritonavir (nirmatrelvir/r) or remdesivir) use, drug–drug interactions (DDIs) and adverse drug reactions (ADRs) in elderly patients (75 and over), hospitalized with mild-to-moderate COVID-19 between July 2022 and June 2023. (3) Results: Out of 491 patients (mean age: 86.9 years), 180 (36.7%) received nirmatrelvir/r, 78 (15.9%) received remdesivir, and 233 (47.4%) received no antiviral therapy. No association was found between the choice of antiviral and the demographic or medical data. No serious ADR was observed. Nirmatrelvir/r dosage adjustment was inadequate in 65% of patients with renal impairment. In total, 128 patients (71%) on nirmatrelvir/r had potential pharmacokinetic DDIs, with 43 resulting in a possibly related ADR. In the remdesivir group, pharmacodynamic DDIs were more frequent, with QTc prolongation risk in 56 patients (72%). Only 20 patients underwent follow-up ECG, revealing QTc prolongation in 4. (4) Conclusions: There is an underutilization of antivirals despite their justified indications. Nirmatrelvir/r dosage was rarely adjusted to renal function. Dose adjustments and closer monitoring are needed due to the high risk of drug interactions.