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PURPOSE: 18F-Flotufolastat (18F-rhPSMA-7.3) is a newly approved prostate-specific membrane antigen targeting radiopharmaceutical for diagnostic imaging of prostate cancer (PCa). SPOTLIGHT (National Clinical Trials 04186845) evaluated 18F-flotufolastat in men with suspected PCa recurrence. Here, we present results of predefined exploratory endpoints from SPOTLIGHT to evaluate the impact of clinical factors on 18F-flotufolastat detection rates (DR). METHODS AND MATERIALS: The impact of baseline prostate-specific antigen (PSA), PSA doubling time (PSAdt), and International Society of Urologic Pathology Grade Group (GG) on 18F-flotufolastat DR was evaluated among all SPOTLIGHT patients with an evaluable scan, with DR stratified according to the patients prior treatment (radical prostatectomy ± radiation therapy [RP] or radiation therapy only [RT]). The patients underwent positron emission tomography 50 to 70 minutes after receiving 18F-flotufolastat (296 MBq IV), and scans were read by 3 blinded central readers, with the majority read representing agreement between ≥2 readers. RESULTS: In total, 389 men (median PSA: 1.10 ng/mL) were evaluable. By majority read, 18F-flotufolastat identified distant lesions in 39% and 43% of patients treated with prior RP or RT, respectively. The overall DR broadly increased with increasing PSA (

With the development of the hyperspectral remote sensing technique, extensive chemical weathering profiles have been identified on Mars. These weathering sequences, formed through precipitation-driven leaching processes, can reflect the paleoenvironments and paleoclimates during pedogenic processes. The specific composition and stratigraphic profiles mirror the mineralogical and chemical trends observed in weathered basalts on Hainan Island in south China. In this study, we investigated the laboratory reflectance spectra of a 53-m-long drilling core of a thick basaltic weathering profile collected from Hainan Island. We established a quantitative spectral model by combining the genetic algorithm and partial least squares regression (GA-PLSR) to predict the chemical properties (SiO2, Al2O3, Fe2O3) and index of laterization (IOL). The entire sample set was divided into a calibration set of 25 samples and a validation set of 12 samples. Specifically, the GA was used to select the spectral subsets for each composition, which were then input into the PLSR model to derive the chemical concentration. The coefficient of determination (R2) values on the validation set for SiO2, Al2O3, Fe2O3, and the IOL were greater than 0.9. In addition, the effects of various spectral preprocessing techniques on the model accuracy were evaluated. We found that the spectral derivative treatment boosted the prediction accuracy of the GA-PLSR model. The improvement achieved with the second derivative was more pronounced than when using the first derivative. The quantitative model developed in this work has the potential to estimate the contents of similar weathering basalt products, and thus infer the degree of alteration and provide insights into paleoclimatic conditions. Moreover, the informative bands selected by the GA can serve as a guideline for designing spectral channels for the next generation of spectrometers.

Veronika Hola,1 Hana Polanska,1 Tereza Jandova,1 Jana Jaklová Dytrtová,1 Josefina Weinerova,2 Michal Steffl,1 Veronika Kramperova,1 Klara Dadova,1 Krzysztof Durkalec-Michalski,3 Ales Bartos2,4 1Faculty of Physical Education and Sport, Charles University, Prague, Czech Republic; 2University Hospital Kralovske Vinohrady, Department of Neurology, Prague, Czech Republic; 3Department of Sports Dietetics, Poznan University of Physical Education, Pozna&nacute;, 61-871, Poland; 4Third Faculty of Medicine, Charles University, Department of Neurology, Prague, Czech RepublicCorrespondence: Michal Steffl, Faculty of Physical Education and Sport Charles University, José Martího 31, Prague, 162 52, Czech Republic, Tel +420778701882, Email michal.steffl@ftvs.cuni.czBackground: Maintaining healthy brain function during ageing is of great importance, especially for the self-sufficiency of older adults. The main aim of this study was to determine the effects of dance and martial arts on exerkines Brain Derived Neurotrophic Factor (BDNF) and irisin blood serum levels.Methods: This randomized controlled trial examined the effects of dance and martial arts on serum Brain-Derived Neurotrophic Factor (BDNF) and irisin levels, as well as cognitive function, mood, and physical measures in older adults. Seventy-seven independently living older adults (mean age 70.3± 3.8 years) were randomized into three groups: dance (DG), martial arts (MaG), and control (CG), followed over 12 weeks. Generalized linear models were used to assess the interventions’ effects.Results: There was a significant increase in BDNF levels in both the DG (1.8 ± 4.9, p < 0.05) and MaG (3.5 ± 6.3, p < 0.05), while CG experienced a decrease (− 4.9 ± 8.2, p < 0.05). Between-group effects were significant for BDNF, with DG and MaG showing higher levels than CG (p < 0.05). No significant changes in irisin levels were found. Cognitive performance, particularly attention and mental flexibility (measured by the Trail Making Test A and B), significantly improved in the DG compared to CG (p < 0.05). Additionally, participants in DG showed improved mood based on the Geriatric Depression Scale (p < 0.05) compared to CG. Anthropometric T-scores were significantly associated with changes in irisin levels (p < 0.05) after intervention.Conclusion: The study found that dance and martial arts upregulated BDNF levels, with dance showing notable improvements in cognitive function and mood in older adults. Changes in anthropometric measures were linked to increased irisin levels. These findings suggest that both dance and martial arts may promote healthy brain function in aging populations.Trial Registration: NCT05363228.Keywords: cognitive domains, ageing, cognitive performance, cognitive function, serum, biomarkers

Abstract We developed and evaluated the Digital Platform for Exercise (DPEx): a decentralized, patient-centric approach designed to enhance all aspects of clinical investigation of exercise therapy. DPEx integrated provision of a treadmill with telemedicine and remote biospecimen collection permitting all study procedures to be conducted in patient’s homes. Linked health biodevices enabled high-resolution monitoring of lifestyle and physiological response. Here we describe the rationale and development of DPEx as well as feasibility evaluation in three different cohorts of patients with cancer: a phase 0a development study among three women with post-treatment primary breast cancer; a phase 0b proof-of-concept trial of neoadjuvant exercise therapy in 13 patients with untreated solid tumors; and a phase 1a level-finding trial of neoadjuvant exercise therapy in 53 men with localized prostate cancer. Collectively, our study demonstrates the utility of a fully digital, decentralized approach to conduct clinical trials of exercise therapy in a clinical population.

Abstract Combining the frameworks of fundamental causes theory and diffusion of innovation, scholars had anticipated a delayed COVID-19 vaccination uptake for people in lower socioeconomic position depending on the socioeconomic context. We qualify these propositions and analyze educational differences in COVID-19 vaccination status over the first ten months of Germany’s vaccination campaign in 2021. Data from the study “Corona Monitoring Nationwide” (RKI-SOEP-2), collected between November 2021 and February 2022, is linked with district-level data of the German Index of Socioeconomic Deprivation (GISD). We estimated the proportion of people with at least one vaccination dose stratified by educational groups and within different settings of regional socioeconomic deprivation at three time points. Logistic multilevel regression models were applied to adjust for multiple covariates and to test cross-level-interactions between educational levels and levels of area-level socioeconomic deprivation. Vaccination rates were lower among respondents with lower education. With increasing area-level socioeconomic deprivation, educational differences were larger due to particularly low vaccination rates in groups with low education levels. The analysis of vaccination timing reveals that educational gaps and gaps by area-level socioeconomic deprivation had appeared early in the vaccination campaign and did not close completely before the 4th wave of COVID-19 infections

Abstract Background This monocentric randomized controlled pilot trial investigates the impact of virtual reality (VR) hypnosedation on perioperative anxiety, pain, patient satisfaction, and medication usage during port implantation under local anesthesia. Methods A total of 120 patients undergoing elective port implantation between January 2022 and August 2023 were enrolled and randomized in a 1:1 ratio to either a VR hypnosedation group or a control group. The VR group used a commercially available VR headset with the HypnoVR application, providing various environments, musical backgrounds, and a guiding voice, while the control group underwent the procedure without VR. Patients with ASA > 3, chronic pain, cognitive issues, and contraindications against VR use were excluded. The main outcomes measured were perioperative pain and anxiety scores, with secondary outcomes including perioperative medication usage. Due to the nature of the interventions, blinding of patients and physicians was not feasible. Statistical analysis was primarily descriptive and exploratory, focusing on estimating effect sizes for future trials. Results The study found no significant differences in immediate postoperative pain with 1.43 ± 1.63 vs. 1.6 ± 2.05 (p = 0.62) or anxiety scores 30.65 ± 9.13 vs. 31.78 ± 13.34 (p = 0.60) between the no VR and VR group, respectively. Additionally, there was a trend to less usage of certain medications, particularly remifentanil (mean dose of 200 mg vs. 100 mg (p = 0.12)) and novaminsulfon (mean dose of 1250 mg vs. 900 mg (p = 0.26)) in the VR group vs. no VR group, respectively. However, these differences were not statistically significant and therefore no definitive conclusions can be drawn regarding medication usage based on this data. Conclusion While VR hypnosedation did not significantly reduce perioperative pain or anxiety in this pilot trial, the observed trends in reduced medication usage suggest potential benefits. These findings warrant further investigation in larger, confirmatory trials to better understand the role of VR in enhancing patient comfort and potentially reducing reliance on pharmacological interventions during surgical procedures. Trial registration German Clinical Trials Register: DRKS00028508; registration date 15 March 2022; Universal Trial Number: U1111-1275–4995.

Background: A chronic disease occurring in a person’s life is a stressor, disrupting every aspect of their life. Objectives: This study aims to assess the relationship between functioning in chronic illness and quality of life with the prevalence of symptoms of depression and anxiety in patients with high cardiovascular risk. Material and methods: This study included 200 patients (aged 18–80 years) under the care of a primary care physician, diagnosed with hypertension and/or hypercholesterolemia, and/or diabetes between 6 and 24 months before the enrollment. The presented analysis assessed the symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS); and the quality of life of patients with cardiovascular disease using the Heart Quality of Life (HeartQoL) questionnaire and functioning in chronic illness using the Functioning in Chronic Illness Scale (FCIS). Results: The HADS scores amounted to 4.34 ± 3.414 points for the HADS-Anxiety subscale and 3.20 ± 2.979 points for the HADS-Depression subscale. The score indicative of functioning in chronic illness assessed with the FCIS was 98.32 ± 13.89 points. The independent predictors of HADS-anxiety were HeartQoL Emotional and FCIS Global, while HeartQoL Global and FCIS Global were the independent predictors for HADS-depression. Better functioning in chronic illness (FCIS Global) was associated with less frequent symptoms of anxiety and depression based on the HADS: HADS-Anxiety (R Spearmann = −0.3969; p < 0.0001) and HADS-Depression (R Spearmann = −0.5884; p < 0.0001). Higher HeartQoL scores, both globally, as well as in emotional and physical dimensions, were associated with a lower severity of anxiety and depression assessed with the HADS: HADS-Anxiety (R Spearmann = −0.2909; p = 0.0001) and HADS-Depression (R Spearmann = −0.2583; p = 0.0002). Conclusions: The quality of life and functioning in chronic illness are connected with symptoms of depression and anxiety. When assessing the severity of the depression symptoms in relation to the individual aspects of functioning in chronic illness, the areas requiring supportive-educational intervention can be identified. The assessment of both functioning in a chronic disease and the severity of the depression symptoms should be included in a standard nursing diagnosis and further supportive and educational intervention.

Abstract Herein, we report polyphosphonate covalent organic frameworks (COFs) constructed via P-O-P linkages. The materials are synthesized via a single-step condensation reaction of the charge-assisted hydrogen-bonded organic framework, which is constructed from phenylphosphonic acid and 5,10,15,20‐tetrakis[p‐phenylphosphonic acid]porphyrin and is formed by simply heating its hydrogen-bonded precursor without using chemical reagents. Above 210 °C, it becomes an amorphous microporous polymeric structure due to the oligomerization of P-O-P bonds, which could be shown by constant-time solid-state double-quantum 31P nuclear magnetic resonance experiments. The polyphosphonate COF exhibits good water and water vapor stability during the gas sorption measurements, and electrochemical stability in 0.5 M Na2SO4 electrolyte in water. The reported family of COFs fills a significant gap in the literature by providing stable microporous COFs suitable for use in water and electrolytes. Additionally, we provide a sustainable synthesis route for the COF synthesis. The narrow pores of the COF effectively capture CO2.

With the advancement of computational network science, its research scope has significantly expanded beyond static graphs to encompass more complex structures. The introduction of streaming, temporal, multilayer, and hypernetwork approaches has brought new possibilities and imposed additional requirements. For instance, by utilising these advancements, one can model structures such as social networks in a much more refined manner, which is particularly relevant in simulations of the spreading processes. Unfortunately, the pace of advancement is often too rapid for existing computational packages to keep up with the functionality updates. This results in a significant proliferation of tools used by researchers and, consequently, a lack of a universally accepted technological stack that would standardise experimental methods (as seen, e.g., in machine learning). This article addresses that issue by presenting an extended version of the Network Diffusion library. First, a survey of the existing approaches and toolkits for simulating spreading phenomena is shown, and then, an overview of the framework functionalities. Finally, we report four case studies conducted with the package to demonstrate its usefulness: the impact of sanitary measures on the spread of COVID-19, the comparison of information diffusion on two temporal network models, and the effectiveness of seed selection methods in the task of influence maximisation in multilayer networks. We conclude the paper with a critical assessment of the library and the outline of still awaiting challenges to standardise research environments in computational network science.

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendalls tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendalls tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.

PURPOSE: Intermediate-risk prostate cancer is a heterogeneous disease state with diverse treatment options. The 22-gene Decipher genomic classifier (GC) retrospectively has shown to improve risk stratification in these patients. We assessed the performance of the GC in men with intermediate-risk disease enrolled in NRG Oncology/RTOG 01-26 with updated follow-up. METHODS AND MATERIALS: After National Cancer Institute approval, biopsy slides were collected from NRG Oncology/RTOG 01-26, a randomized phase 3 trial of men with intermediate-risk prostate cancer randomized to 70.2 Gy versus 79.2 Gy of radiation therapy without androgen deprivation therapy. RNA was extracted from the highest-grade tumor foci to generate the locked 22-gene GC model. The primary endpoint for this ancillary project was disease progression (composite of biochemical failure, local failure, distant metastasis, prostate cancer-specific mortality, and use of salvage therapy). Individual endpoints were also assessed. Fine-Gray or cause-specific Cox multivariable models were constructed adjusting for randomization arm and trial stratification factors. RESULTS: Two-hundred fifteen patient samples passed quality control for analysis. The median follow-up was 12.8 years (range, 2.4-17.7). On multivariable analysis, the 22-gene GC (per 0.1 unit) was independently prognostic for disease progression (subdistribution hazard ratio [sHR], 1.12; 95% confidence interval [CI], 1.00-1.26; P = .04), biochemical failure (sHR, 1.22; 95% CI, 1.10-1.37; P < .001), distant metastasis (sHR, 1.28; 95% CI, 1.06-1.55; P = .01), and prostate cancer-specific mortality (sHR, 1.45; 95% CI, 1.20-1.76; P < .001). Ten-year distant metastasis in GC low-risk patients was 4% compared with 16% for GC high-risk patients. In patients with lower GC scores, the 10-year difference in metastasis-free survival rate between arms was -7%, compared with 21% for higher GC patients (P-interaction = .04). CONCLUSIONS: This study represents the first validation of a biopsy-based gene expression classifier, assessing both its prognostic and predictive value, using data from a randomized phase 3 trial of intermediate-risk prostate cancer. Decipher improves risk stratification and can aid in treatment decision-making in men with intermediate-risk disease.

Abstract Objective Deep vein thrombosis (DVT) is discussed as a source of embolism for cerebral ischemia in the presence of patent foramen ovale (PFO). However, previous studies reported varying rates of DVT in stroke patients, and recommendations for screening are lacking. This study aimed to characterize patients with stroke or transient ischemic attack (TIA) and concomitant PFO and explore the rate of DVT and associated parameters. Methods Medical records were screened for patients with stroke or TIA and echocardiographic evidence of PFO. Concomitant DVT was identified according to compression ultrasonography of the lower limbs. A variety of demographic, clinical, and laboratory parameters, the RoPE and Wells scores were compared between patients with and without DVT. Results Three-hundred-thirty-nine patients (mean age 61.2 ± 15.4 years, 61.1% male) with stroke or TIA and PFO, treated between 01/2015 and 12/2020, were identified. Stroke and TIA patients did not differ for demographic and vascular risk factors. DVT was found in 17 cases out of 217 (7.8%) with compression ultrasonography. DVT was associated with a history of DVT, cancer, previous immobilization, calf compression pain, calf circumference difference, and a few laboratory abnormalities, e.g., increased D-dimer. A multivariate regression model with stepwise backward selection identified the Wells score (odds ratio 35.46, 95%-confidence interval 4.71–519.92) as a significant predictor for DVT. Conclusion DVT is present in a relevant proportion of patients with cerebral ischemia and PFO, which needs to be considered for the individual diagnostic workup. The Wells score seems suitable for guiding additional examinations, i.e., compression ultrasonography.

In this study, the uncertainty of measurement paths was estimated using selected statistical methods. Specifically, temperature measurements obtained from contact temperature sensors used in a heat transfer test section were investigated. The experiments utilized a drywell temperature calibrator, thermoelements (types K, J, N, and T), and a data acquisition station. Additionally, a certified Pt-100 resistance sensor connected to the temperature meter was considered during measurements. The temperature range for the selected measurement points was 0.3 to 100 °C, covering both increasing and decreasing temperatures. To calculate the expanded uncertainty, both the uncertainty propagation method and the Monte Carlo method were employed. The results were analyzed and found to be similar.

Abstract Modern Mars is bipolar, cold, and oxidizing, while early Mars was characterized by icy highlands, episodic warmth and reducing atmosphere. The timing and association of the climate and redox transitions remain inadequately understood. Here we examine the spatiotemporal distribution of the low surface iron abundance in the ancient Martian terrains, revealing that iron abundance decreases with elevation in the older Noachian terrains but with latitude in the younger Noachian terrains. These observations suggest: (a) low-temperature conditions contribute to surface iron depletion, likely facilitated by anoxic leaching through freeze-thaw cycles under a reducing atmosphere, and (b) temperature distribution mode shifted from elevation-dominant to latitude-dominant during the Noachian period. Additionally, we find iron leaching intensity decreases from the Early to Late Noachian epoch, suggesting a gradual atmospheric oxidation coupled with temperature mode transition during the Noachian period. We think atmospheric oxidation led to Mars becoming cold and bipolar in its early history.

&Lstrok;ukasz Pietrzykowski,1,&ast; Agata Kosobucka-Ozdoba,1,&ast; Piotr Michalski,1 Micha&lstrok; Kasprzak,2 Jakub Ratajczak,1 Alicja Rzepka-Cholasi&nacute;ska,1 Joanna Siódmiak,3 Klaudyna Grzelakowska,2 Aldona Kubica1 1Department of Cardiac Rehabilitation and Health Promotion, Nicolaus Copernicus University in Toru&nacute;, Collegium Medicum in Bydgoszcz, Poland; 2Department of Cardiology and Internal Medicine, Nicolaus Copernicus University in Toru&nacute;, Collegium Medicum in Bydgoszcz, Poland; 3Department of Laboratory Medicine, Nicolaus Copernicus University in Toru&nacute;, Collegium Medicum in Bydgoszcz, Poland&ast;These authors contributed equally to this workCorrespondence: &Lstrok;ukasz Pietrzykowski, Department of Cardiac Rehabilitation and Health Promotion, Nicolaus Copernicus University in Toru&nacute;, Collegium Medicum in Bydgoszcz, Ul. M. Sk&lstrok;odowskiej Curie 9, Bydgoszcz, 85-094, Poland, Tel +48525855835, Email lukasz.pietrzykowski@cm.umk.plBackground: Anxiety and depression by affecting lifestyle interfere with preventive actions aimed at eliminating or reducing modifiable risk factors for cardiovascular diseases (CVD).Purpose: The objective of the study was to assess the impact of anxiety and depression on the achievement of therapeutic goals regarding CVD risk factors in patients without a history of atherosclerotic CVD.Patients and Methods: The study included 200 patients (median age 52.0 [IQR 43.0– 60.5] years). Control of the basic risk factors was assessed: blood pressure, BMI, waist circumference, physical activity, smoking status, LDL cholesterol, triglycerides, and blood glucose. The data analysis included a comparison of the number of controlled risk factors and the percentage of subjects who achieved the therapeutic goal for each of the cardiovascular risk factors. The risk of CVD was assessed with SCORE2 and SCORE2-OP. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). On both subscales (HADS Anxiety and HADS Depression), subjects could achieve normal, borderline, and abnormal scores.Results: The median number of controlled CVD risk factors was 4.0 (IQR 3.0– 5.0), and the median CVD risk assessed with SCORE2 and SCORE2-OP was 3.0% (IQR 1.5– 7.0%). Median scores for HADS Anxiety were 3.0 (IQR 2.0– 6.0) and for HADS Depression 3.0 (1.0– 5.0). Patients with symptoms of anxiety and depression had significantly fewer controlled risk factors (HADS Anxiety p=0.0014; HADS Depression p=0.0304). Among subjects with anxiety and depression, there was a significantly lower percentage of those with a normal waist circumference (HADS Anxiety p=0.0464; HADS Depression p=0.0200) and regular physical activity (HADS Anxiety p=0.0431; HADS Depression p=0.0055). Among subjects with anxiety, there was a significantly lower percentage of those with a normal BMI (p=0.0218) and normal triglyceride concentrations (p=0.0278).Conclusion: The presence of anxiety and depression may affect the control of CVD risk factors in individuals without a history of atherosclerotic CVD. Assessment of anxiety and depression symptoms should be part of a comprehensive examination of patients with high CVD risk.Keywords: anxiety, depression, cardiovascular diseases, risk factors

Objectives Examining similarities and differences in road behavior and knowledge about selected aspects of road safety in two different age groups of pedestrians, i.e. people under 18 and over 65 years of age. Material and methods The analysis is based on a study conducted using a survey questionnaire in the period December 20, 2022 - June 1, 2023. 625 people took part in the study, 268 people under 18 and 357 people over 65. Results Research shows that both groups tend to engage in dangerous behaviors. Young people are more likely to cross the road in unauthorized places and to cross pedestrian crossings without traffic lights, using mobile phones and headphones. Older people are less likely to wear reflective elements. Awareness of selected threats in both age groups is low. Conclusions The research shows that both young and older people do not always behave safely on the road. People under 18 are more often responsible for dangerous behavior at pedestrian crossings. Another important problem is the lack of proper knowledge about the threats to which pedestrians are exposed and the lack of awareness of dangerous situations. In this study, most respondents were not aware of the dangers posed, partly due to their inappropriate behavior. Most questions regarding possible threats were answered incorrectly almost every time by over half of respondents in both age groups. None of the surveyed groups has an advantage regarding road traffic hazards. People under 18 more often correctly answered questions about priority at a pedestrian crossing and the driver's reaction time to the appearance of a live obstacle. People over 65 more often indicated the correct answer regarding the braking distance and the distance covered by a driver traveling at a speed of 50 km/h.

Accumulation of DNA sequence data and its use in systematics of the family Argasidae reveals new incongruencies between genera and subgenera, since several groups defined by classical taxonomy appear to be paraphyletic, which is the case of the subgenus Pavlovskyella. In order to identify morphological characters unique to one of the monophyletic groupings within Pavlovskyella and improve its system, we describe all active stages of Ornithodoros (Pavlovskyella) tartakovskyi, a species with an incomplete original description. Larvae, nymphs, males and females from Iran were examined with scanning electron microscopy (SEM). The larva of O. (P.) tartakovskyi lacks dorsal plate, posteromedian seta, postcoxal setae and a spinose area in palpal article I; the dorsal surface has 13 pairs of setae and the hypostome has two short rows of denticles in the apex only. The first nymphal instar (N1) has a micromammillated body with faint dorsal and ventral disks. The second nymphal instar (N2) shows mammillated body with an incipient hood, and dorsal disks outlined as in subsequent instars. Both N1 and N2 have a small patch of glabrous surface in the anterior margin of preanal groove, absent in posterior stages. Third nymphal instar (N3) has a small hood and lack cheeks, which are incipient in the fourth nymphal instar (N4). The four nymphal instars (N1–N4) have blunt hypostomes, striated capitula, non-mammillated legs, and 3 humps on tarsi I. Females and males of O. (P.) tartakovskyi have mammillated bodies, small cheeks not covering the capitulum, the anteromedian disk is placed anteriorly to anterior central disks, and a posterior median file of disks is merged with the median disk. We describe all postembryonic stages of O. (P.) tartakovskyi providing morphological characters that define Pavlovskyella sensu stricto and Theriodoros, a sister subgenus that includes similarly shaped species.

Background: Despite some recent advances, pancreatic ductal adenocarcinoma (PDAC) remains a growing oncological challenge. New drugs capable of targeting more than one oncogenic pathway may be one way to improve patient outcomes. This study characterizes the effectiveness of Metavert a first-in-class dual inhibitor of GSK3-β and histone deacetylase in treating PDAC as a single agent or in combination with standard cytotoxics. Methods: Thirty-six Patient-Derived Organoids (hPDOs) characterised by RNASeq and whole exome sequencing were treated with Metavert alone or in combination with standard cytotoxics. Transcriptomic signatures (TS) representing sensitivity to Metavert alone or sensitivity to Metavert + irinotecan (IR) were evaluated in 47 patient samples, chemo-naïve in 26 and post-chemotherapy in 21 (gemcitabine=5; FOLFIRINOX=14, both=2) with companion multiplexed immunofluorescence and RNASeq data. Results: Metavert combined with gemcitabine, irinotecan, 5FU, oxaliplatin, and paclitaxel was synergistic in the hPDOs. Basal-subtype hPDOs were more sensitive to Metavert alone whereas the Metavert+IR combination exhibited synergy in Classical-subtype hPDOs with increased apoptosis and autophagy. hPDO-derived TS evaluated in PDAC tissues demonstrated that Metavert-TSHi samples were enriched for mRNA splicing and DNA repair processes; they were associated with Basal-like tissues but also with GATA6+ve-chemo-naïve samples and were higher following gemcitabine but not FOLFIRINOX treatment. In contrast, Metavert+IR-TSHI samples were enriched for TP53 pathways; they were associated with Classical-like pretreatment samples and with GATA6+ve/KRT17+ve hybrid cell types following FOLFIRINOX, but not gemcitabine treatment, and were unrelated to transcriptional subtypes. Conclusions: Metavert as a single agent and in combination with irinotecan offers novel strategies for treating pancreatic cancer.