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Iris Haimov,1,* Faiga Magzal,2,3,* Snait Tamir,2,3 Maya Lalzar,4 Kfir Asraf,1 Uzi Milman,5 Maayan Agmon,6,* Tamar Shochat6,* 1Department of Psychology and the Center for Psychobiological Research, The Max Stern Yezreel Valley College, Yezreel Valley, Israel; 2Laboratory of Human Health and Nutrition Sciences, MIGAL-Galilee Research Institute, Kiryat Shmona, Israel; 3Nutritional Science Department, Tel Hai College, Kiryat Shmona, Israel; 4Bioinformatics Service Unit, University of Haifa, Haifa, Israel; 5Clinical Research Unit, Clalit Health Services, Haifa, Israel; 6The Cheryl Spencer Department of Nursing, University of Haifa, Haifa, Israel*These authors contributed equally to this workCorrespondence: Iris Haimov, Department of Psychology and the Center for Psychobiological Research, the Max Stern Yezreel Valley College, Yezreel Valley, 1930600, Israel, Email i_haimov@yvc.ac.ilPurpose: Insomnia, a chronic condition affecting 50% of older adults, is often accompanied by cognitive decline. The mechanism underlying this comorbidity is not fully understood. A growing literature suggests the importance of gut microbiota for brain function. We tested associations between sleep quality and cognitive performance with gut microbiota in older adults with insomnia.Patients and Methods: Seventy-two older adults with insomnia (age 73.2 ± 5.73 years, 56 females) provided stool samples for gut microbial sequencing. Microbiota profile was determined using the DADA2 bioinformatics pipeline. Cognition was assessed with the Cambridge Neuropsychological Test Automated Battery. Objective sleep quality was monitored by a two-week actigraphic recording, and participants completed the Insomnia Severity Index (ISI). We used partial canonical correspondence analysis (pCCA) to examine the relative contribution of insomnia, based on actigraphic sleep efficiency (SE) and ISI, and of cognitive status, based on the Multitasking test of Median Reaction Latency (MTTLMD) and the Spatial Working Memory Between Errors (SWMBE), to variance in microbiota composition. We used Pearson correlations to correlate insomnia and cognitive status parameters with microbiota amplicon sequence variants, genera, and families.Results: The pCCA revealed that sleep quality and cognitive performance explained a variation of 7.5– 7.9% in gut microbiota composition in older adults with insomnia. Correlation analysis demonstrated that Lachnoclostridium (genus) correlates positively with SE (r=0.42; P=0.05) and negatively with MTTLMD (r=− 0.29; P=0.03), whereas Blautia (genus) correlates negatively with MTTLMD (r=− 0.31; P=0.01).Conclusion: Findings demonstrate the associations of sleep quality and cognitive performance with variance in gut microbiota composition and with specific genus abundance in older adults with insomnia. Further studies should validate the findings, determine causal relationships, and evaluate potential interventions for the comorbidity of insomnia and cognitive impairment in older adults with insomnia.Keywords: actigraphy, cognition, older adults, microbiome, sleep efficiency

Primary hepatocyte transplantation (HTx) is a safe cell therapy for patients with liver disease, but wider application is circumvented by poor cell engraftment due to limitations in hepatocyte quality and transplantation strategies. Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (hiPSC) are considered a promising alternative but also require optimisation of transplantation and are often transplanted prior to full maturation. Whole-body in vivo imaging would be highly beneficial to assess engraftment non-invasively and monitor the transplanted cells in the short and long-term.Here we report a lentiviral transduction approach designed to engineer hiPSC-derived HLCs during differentiation. This strategy resulted in the successful production of sodium iodide symporter (NIS)-expressing HLCs that were functionally characterised, transplanted into mice, and subsequently imaged using radionuclide tomography. Keywords: Cell tracking, Hepatocyte-like cells, Human sodium iodide symporter, Induced pluripotent stem cells, Lentivirus, Radionuclide imaging

Abstract Jet mixing is a critical factor in various engineering applications, influencing pollutant dispersion, chemical processes, medical treatments, and combustion enhancement. Hitherto, jet mixing has typically been optimized by either passive or active control techniques. In this experimental study, we combine simultaneous optimization of active control with 12 inward-pointing minijets and a tuneable nozzle exit shape commanded by 12 stepper motors. Jet mixing is monitored at the end of the potential core with an array of 7 $$\times$$ 7 Pitot tubes. This high-dimensional actuation space is conquered with Particle Swarm Optimization through Targeted, Position-Mutated Elitism. Our results underscore the significant impact of combining control techniques, illustrating the complex interactions of both passive and active control on jet flow dynamics. The mixing area of the combined control optimization is 4.5 times larger than the area of the unforced state. This mixing increase significantly outperforms the effect of shape optimization of the nozzle alone. Our study points at the potential of optimization in high-dimensional design spaces for shapes as well as passive and active control—leveraging the rapid development of flow control hardware and the increasingly powerful tools of artificial intelligence for optimization.

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Introduction/backgroundPhosphatase and tensin homolog (PTEN) genomic deletions and transmembrane protease, serine 2/v-ets avian erthyroblastosis virus E26 oncogene homolog (ERG) rearrangements are two of the most common genetic abnormalities associated with prostate cancer. Prior studies have demonstrated these alterations portend worse clinical outcomes. Our objective is to evaluate the impact of biopsy-determined PTEN losses and TMPRSS2-ERG fusion on biochemical progression-free survival (bPFS) and overall survival (OS) in patients who receive SBRT for localized prostate cancer.Methods/materialsPatients received SBRT for localized prostate cancer on a prospective quality-of-life (QoL) and cancer outcomes study. For each patient, the single biopsy core with the highest grade/volume of cancer was evaluated for PTEN and ERG abnormalities. Differences in baseline patient and disease characteristics between groups were analyzed using ANOVA for age and χ2 for categorical groupings. bPFS and OS were calculated using the Kaplan Meier (KM) method with Log-Rank test comparison between groups. Predictors of bPFS and OS were identified using the Cox proportional hazards method. For all analyses, p

Annually, about 300 million surgeries lead to significant intraoperative adverse events (iAEs), impacting patients and surgeons. Their full extent is underestimated due to flawed assessment and reporting methods. Inconsistent adoption of new grading systems and a lack of standardization, along with litigation concerns, contribute to underreporting. Only half of relevant journals provide guidelines on reporting these events, with a lack of standards in surgical literature. To address these issues, the Intraoperative Complications Assessment and Reporting with Universal Standard (ICARUS) Global Surgical Collaboration was established in 2022. The initiative involves conducting global surveys and a Delphi consensus to understand the barriers for poor reporting of iAEs, validate shared criteria for reporting, define iAEs according to surgical procedures, evaluate the existing grading systems' reliability, and identify strategies for enhancing the collection, reporting, and management of iAEs. Invitation to participate are extended to all the surgical specialties, interventional cardiology, interventional radiology, OR Staffs and anesthesiology. This effort represents an essential step towards improved patient safety and the well-being of healthcare professionals in the surgical field.

Limiting the suspension stroke in vehicles holds critical and conceivable benefits. It is crucial for the safety, stability, ride comfort, and overall performance of the vehicle. Furthermore, it improves the reliability of suspension components and maintains consistent handling during regular and rough driving conditions. Hence, the design of a safety-critical controller to limit the suspension stroke for active suspension systems is of high importance. In this study, we employed a quarter-car model that incorporates a suspension spring with cubic nonlinearity. The proposed safety-critical controller is the control Lyapunov function–control barrier function–quadratic programming (CLF-CBF-QP). Initially, we designed the reference controller as a linear quadratic regulator (LQR) controller based on the linearized quarter-car model. The reference state-feedback LQR controller simplified the design of the control Lyapunov function. Consequently, from the nonlinear model, we construct a simple control Lyapunov function that relies only on the sprung mass velocity to have a relative degree of one. The CLF intends to improve the performance by considering the nonlinearity and via online optimization. We then formulate the control barrier function to restrict the suspension stroke from breaching its limits. To assess the effectiveness of the proposed controller, we present two challenging road inputs for the nonlinear quarter-car model when employing CLF-CBF-QP and LQR controllers. The CLF-CBF-QP findings surpassed the LQR controller in terms of safety and performance. This study highlights the immense potential of CLF-CBF-QP for suspension systems, improving the time-domain performance, limiting the suspension stroke, and guaranteeing safety.

PurposeIntensity-modulated radiation therapy (IMRT) with brachytherapy boost for unfavorable prostate cancer has been shown to improve biochemical relapse-free survival compared to IMRT alone. Stereotactic body radiation therapy (SBRT) is a less-invasive alternative to brachytherapy. Early outcomes utilizing SBRT boost suggest low rates of high-grade toxicity with a maintained patient-reported quality of life. Here, we report the 5-year progression-free survival (PFS) and prostate cancer-specific survival (PCSS) of patients treated with IMRT plus SBRT boost.Materials and methodsBetween 2008 and 2020, 255 patients with unfavorable prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45–50.4 Gy) according to an institutional protocol. For the first year, the patient’s PSA level was monitored every 3 months, biannually for 2 years, and annually thereafter. Failure was defined as nadir + 2 ng/mL or a rising PSA with imaging suggestive of recurrence. Detection of recurrence also included digital rectal examination and imaging studies, such as MRI, CT, PET/CT, and/or bone scans. PFS and PCSS were calculated using the Kaplan–Meier method.ResultsThe median follow-up period was 71 months. According to the NCCN risk classification, 5% (13/255) of the patients had favorable intermediate-risk disease, 23% (57/255) had unfavorable intermediate-risk disease, 40% (102/255) had high-risk disease, and 32% (83/255) had very high-risk disease. Androgen deprivation therapy was administered to 80% (204/255) of the patients. Elective pelvic lymph node IMRT was performed in 28 (10%) patients. The PFS for all patients at 5 years was 81% (favorable intermediate risk, 91%; unfavorable intermediate risk, 89%; high-risk, 78%; and very-high risk, 72%). The PCSS for all patients at 5 years was 97% (favorable intermediate risk, 100%; unfavorable intermediate risk, 100%; high risk, 100%; and very high risk, 89%).ConclusionThe incidence of failure following IMRT plus SBRT for unfavorable prostate cancer remains low at 5 years.

ObjectiveTo train and validate the use of a novel artificial intelligence-based thermal imaging system as a screening tool to rule out malignancy in cutaneous and subcutaneous masses in dogs.AnimalsTraining study: 147 client-owned dogs with 233 masses. Validation Study: 299 client-owned dogs with 525 masses. Cytology was non-diagnostic in 94 masses, resulting in 431 masses from 248 dogs with diagnostic samples.ProceduresThe prospective studies were conducted between June 2020 and July 2022. During the scan, each mass and its adjacent healthy tissue was heated by a high-power Light-Emitting Diode. The tissue temperature was recorded by the device and consequently analyzed using a supervised machine learning algorithm to determine whether the mass required further investigation. The first study was performed to collect data to train the algorithm. The second study validated the algorithm, as the real-time device predictions were compared to the cytology and/or biopsy results.ResultsThe results for the validation study were that the device correctly classified 45 out of 53 malignant masses and 253 out of 378 benign masses (sensitivity = 85% and specificity = 67%). The negative predictive value of the system (i.e., percent of benign masses identified as benign) was 97%.Clinical relevanceThe results demonstrate that this novel system could be used as a decision-support tool at the point of care, enabling clinicians to differentiate between benign lesions and those requiring further diagnostics.

Abstract We improve convergence speed by two orders of magnitude and the global exploration capabilities of particle swarm optimization (PSO) through targeted position-mutated elitism (TPME). The proposed fast-converging TPME operator requires a fitness-based classification technique to categorize the particles. The introduced classification is motivated by its simplicity, low memory requirements, and automated termination criteria based on convergence. The three key innovations address particle classification, elitism, and mutation in the cognitive and social model. PSO-TPME is benchmarked against five popular PSO variants for multi-dimensional functions, which are extensively adopted in the optimization field, In particular, the convergence accuracy, convergence speed, and the capability to find global minima are investigated. The statistical error is assessed by numerous repetitions. The simulations confirmed that in ten of the thirteen investigated functions, the proposed PSO variant outperforms other variants in terms of convergence rate and accuracy by at least two orders of magnitude. On the other hand, the simulations demonstrated the early exploration capabilities of PSO-TPME in all tested functions. In the first ten iterations, PSO-TPME outperformed all the investigated PSO variants by at least two orders of magnitude.

Abstract Background The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial is aimed at addressing the urgent need to find effective treatments for patients hospitalised with suspected or confirmed COVID-19. The trial has had many successes, including discovering that dexamethasone is effective at reducing COVID-19 mortality, the first treatment to reach this milestone in a randomised controlled trial. Despite this, it continues to use standard or ‘fixed’ randomisation to allocate patients to treatments. We assessed the impact of implementing response adaptive randomisation within RECOVERY using an array of performance measures, to learn if it could be beneficial going forward. This design feature has recently been implemented within the REMAP-CAP platform trial. Methods Trial data was simulated to closely match the data for patients allocated to standard care, dexamethasone, hydroxychloroquine, or lopinavir-ritonavir in the RECOVERY trial from March-June 2020, representing four out of five arms tested throughout this period. Trials were simulated in both a two-arm trial setting using standard care and dexamethasone, and a four-arm trial setting utilising all above treatments. Two forms of fixed randomisation and two forms of response-adaptive randomisation were tested. In the two-arm setting, response-adaptive randomisation was implemented across both trial arms, whereas in the four-arm setting it was implemented in the three non-standard care arms only. In the two-arm trial, randomisation strategies were performed at the whole trial level as well as within three pre-specified patient subgroups defined by patients’ respiratory support level. Results All response-adaptive randomisation strategies led to more patients being given dexamethasone and a lower mortality rate in the trial. Subgroup specific response-adaptive randomisation reduced mortality rates even further. In the two-arm trial, response-adaptive randomisation reduced statistical power compared to FR, with subgroup level adaptive randomisation exhibiting the largest power reduction. In the four-arm trial, response-adaptive randomisation increased statistical power in the dexamethasone arm but reduced statistical power in the lopinavir arm. Response-adaptive randomisation did not induce any meaningful bias in treatment effect estimates nor did it cause any inflation in the type 1 error rate. Conclusions Using response-adaptive randomisation within RECOVERY could have increased the number of patients receiving the optimal COVID-19 treatment during the trial, while reducing the number of patients needed to attain the same study power as the original study. This would likely have reduced patient deaths during the trial and lead to dexamethasone being declared effective sooner. Deciding how to balance the needs of patients within a trial and future patients who have yet to fall ill is an important ethical question for the trials community to address. Response-adaptive randomisation deserves to be considered as a design feature in future trials of COVID-19 and other diseases.

This paper investigates the effect of employing an inerter on the performance of active suspension systems. A quarter-car model with cubic-nonlinear spring is considered. The inerter is installed in parallel with the primary suspension spring and damper. First, feedback linearization (FBL) is used to linearize the mathematical model. Then the linear quadratic regulator (LQR) is adopted to control the suspension system. The proposed design is ride comfort-oriented and considers structural constraints. Numerical simulations are executed for passive systems with different values of inertance. Results show that employing an inerter to the passive suspension can improve the ride comfort performance by more than 32%. Employing an inerter to active suspension systems can also improve the ride comfort and reduce actuator force significantly. The actuator force can be reduced by 25%. However, the results also show that the uncaring selection of the inerter can dramatically degrade the performance of the suspension system.

Nanocrystalline-twinned materials exhibit significantly higher strength and ductility than nanocrystalline face-centered cubic (f.c.c.) materials without twins. In this investigation, a dislocation-density-based multiple-slip crystalline constitutive and a nonlinear finite element formulation have been used to understand how twin volume fractions, grain and twin orientations and texture, dislocation-density accumulation, and large inelastic strains affect the competing effects of strengthening and toughening mechanisms in nanotwinned materials. The predictions have indicated that grain and twin orientations with respect to different loading axes significantly affect how dislocation densities evolve, and that this has a dominant effect on both ductility and strength. The predictions were validated with experiments pertaining to nanotwinned f.c.c. copper aggregates. The validated predictions can potentially be used as design guidelines for optimizing the mechanical behavior of nanotwinned crystalline materials, such that behavior can be mitigated and controlled at the nanocrystalline scale. [ABSTRACT FROM AUTHOR]