One of the most common statistical analyses in experimental psychology concerns the comparison of two means using the frequentist t test. However, frequentist t tests do not quantify evidence and require various assumption tests. Recently, popularized Bayesian t tests do quantify evidence, but these were developed for scenarios where the two populations are assumed to have the same variance. As an alternative to both methods, we outline a comprehensive t test framework based on Bayesian model averaging. This new t test framework simultaneously takes into account models that assume equal and unequal variances, and models that use t-likelihoods to improve robustness to outliers. The resulting inference is based on a weighted average across the entire model ensemble, with higher weights assigned to models that predicted the observed data well. This new t test framework provides an integrated approach to assumption checks and inference by applying a series of pertinent models to the data simultaneously rather than sequentially. The integrated Bayesian model-averaged t tests achieve robustness without having to commit to a single model following a series of assumption checks. To facilitate practical applications, we provide user-friendly implementations in JASP and via the RoBTT package in R . A tutorial video is available at https://www.youtube.com/watch?v=EcuzGTIcorQ.

• MeSH
• Bayes Theorem MeSH
• Psychology, Experimental * methods   MeSH
• Data Interpretation, Statistical MeSH
• Humans MeSH
• Models, Statistical * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

OBJECTIVE: The study objectives were (i) to explore the agreement between the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and physical examination in assessing enthesitis in patients with spondyloarthritis (SpA) and (ii) to investigate the prevalence and clinical relevance of subclinical enthesitis in this population. METHODS: Twenty rheumatology centers participated in this cross-sectional study. Patients with SpA, including axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for "active enthesitis" by our group. Subclinical enthesitis was defined as the presence of "active enthesitis" in ≥1 enthesis in patients with SpA without clinical enthesitis (ie, number of positive entheses on physical examination and Leeds Enthesitis Index score = 0). RESULTS: A total of 4,130 entheses in 413 patients with SpA (224 with axSpA and 189 with PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (ie, enthesophytes) to almost perfect (ie, power Doppler and "active enthesitis"). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158 (38.3%) of 413 patients with SpA with clinical enthesitis, 108 (68.4%) exhibited no "active enthesitis" on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of patients with SpA with and without subclinical enthesitis. CONCLUSION: Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in patients with SpA.

• MeSH
• Achilles Tendon diagnostic imaging   MeSH
• Axial Spondyloarthritis diagnostic imaging   MeSH
• Adult MeSH
• Enthesopathy * diagnostic imaging   MeSH
• Physical Examination * MeSH
• Middle Aged MeSH
• Humans MeSH
• Cross-Sectional Studies MeSH
• Arthritis, Psoriatic diagnostic imaging   complications   MeSH
• Spondylarthritis * diagnostic imaging   complications   MeSH
• Ultrasonography * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

BACKGROUND: Optimal management of outpatients with heart failure (HF) requires serially updating the estimates of their risk for adverse clinical outcomes to guide treatment. Patient-reported outcomes (PROs) are becoming increasingly used in clinical care. The purpose of this study was to determine whether the inclusion of PROs can improve the risk prediction for HF hospitalization and death in ambulatory patients with HF. METHODS AND RESULTS: We included consecutive patients with HF with reduced ejection fraction (HFrEF) and HF with preserved EF (HFpEF) seen in a HF clinic between 2015 and 2019 who completed PROs as part of routine care. Cox regression with a least absolute shrinkage and selection operator regularization and gradient boosting machine analyses were used to estimate risk for a combined outcome of HF hospitalization, heart transplant, left ventricular assist device implantation, or death. The performance of the prediction models was evaluated with the time-dependent concordance index (Cτ). Among 1165 patients with HFrEF (mean age 59.1 ± 16.1, 68% male), the median follow-up was 487 days. Among 456 patients with HFpEF (mean age 64.2 ± 16.0 years, 55% male) the median follow-up was 494 days. Gradient boosting regression that included PROs had the best prediction performance - Cτ 0.73 for patients with HFrEF and 0.74 in patients with HFpEF, and showed very good stratification of risk by time to event analysis by quintile of risk. The Kansas City Cardiomyopathy Questionnaire overall summary score, visual analogue scale and Patient Reported Outcomes Measurement Information System dimensions of satisfaction with social roles and physical function had high variable importance measure in the models. CONCLUSIONS: PROs improve risk prediction in both HFrEF and HFpEF, independent of traditional clinical factors. Routine assessment of PROs and leveraging the comprehensive data in the electronic health record in routine clinical care could help more accurately assess risk and support the intensification of treatment in patients with HF.

• MeSH
• Risk Assessment methods   MeSH
• Patient Reported Outcome Measures * MeSH
• Hospitalization statistics & numerical data   MeSH
• Quality of Life * psychology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Heart Failure * physiopathology   psychology   therapy   diagnosis   mortality   MeSH
• Stroke Volume physiology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

The formation of memories is a complex, multi-scale phenomenon, especially when it involves integration of information from various brain systems. We have investigated the differences between a novel and consolidated association of spatial cues and amphetamine administration, using an in situ hybridisation method to track the short-term dynamics during the recall testing. We have found that remote recall group involves smaller, but more consolidated groups of neurons, which is consistent with their specialisation. By employing machine learning analysis, we have shown this pattern is especially pronounced in the VTA; furthermore, we also uncovered significant activity patterns in retrosplenial and prefrontal cortices, as well as in the DG and CA3 subfields of the hippocampus. The behavioural propensity towards the associated localisation appears to be driven by the nucleus accumbens, however, further modulated by a trio of the amygdala, VTA and hippocampus, as the trained association is confronted with test experience. Moreover, chemogenetic analysis revealed central amygdala as critical for linking appetitive emotional states with spatial contexts. These results show that memory mechanisms must be modelled considering individual differences in motivation, as well as covering dynamics of the process.

• MeSH
• Amphetamine pharmacology   MeSH
• Amygdala physiology   MeSH
• Hippocampus * physiology   MeSH
• Memory Consolidation * physiology   MeSH
• Rats MeSH
• Brain physiology   MeSH
• Neurons physiology   metabolism   MeSH
• Nucleus Accumbens * physiology   MeSH
• Reward * MeSH
• Memory physiology   MeSH
• Cues MeSH
• Prefrontal Cortex physiology   MeSH
• Mental Recall * physiology   MeSH
• Machine Learning MeSH
• Ventral Tegmental Area * physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Clear-cell renal cell carcinoma (ccRCC) is a common urological malignancy with an increasing incidence. The development of molecular biomarkers that can predict the response to treatment and guide personalized therapy selection would substantially improve patient outcomes. Dysregulation of non-coding RNA (ncRNA) has been shown to have a role in the pathogenesis of ccRCC. Thus, an increasing number of studies are being carried out with a focus on the identification of ncRNA biomarkers in ccRCC tissue samples and the connection of these markers with patients' prognosis, pathological stage and grade (including metastatic potential), and therapy outcome. RNA sequencing analysis led to the identification of several ncRNA biomarkers that are dysregulated in ccRCC and might have a role in ccRCC development. These ncRNAs have the potential to be prognostic and predictive biomarkers for ccRCC, with prospective applications in personalized treatment selection. Research on ncRNA biomarkers in ccRCC is advancing, but clinical implementation remains preliminary owing to challenges in validation, standardization and reproducibility. Comprehensive studies and integration of ncRNAs into clinical trials are essential to accelerate the clinical use of these biomarkers.

• MeSH
• Carcinoma, Renal Cell * genetics   diagnosis   MeSH
• Humans MeSH
• Biomarkers, Tumor * genetics   MeSH
• Kidney Neoplasms * genetics   diagnosis   MeSH
• RNA, Untranslated * genetics   MeSH
• Prognosis MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Gene Expression Profiling MeSH
• Transcriptome * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The small-molecule alkaloid halofuginone (HF) is obtained from febrifugine. Recent studies on HF have aroused widespread attention owing to its universal range of noteworthy biological activities and therapeutic functions, which range from parasite infections and fibrosis to autoimmune diseases. In particular, HF is believed to play an excellent anticancer role by suppressing the proliferation, adhesion, metastasis, and invasion of cancers. This review supports the goal of demonstrating various anticancer effects and molecular mechanisms of HF. In the studies covered in this review, the anticancer molecular mechanisms of HF mainly included transforming growth factor-β (TGF-β)/Smad-3/nuclear factor erythroid 2-related factor 2 (Nrf2), serine/threonine kinase proteins (Akt)/mechanistic target of rapamycin complex 1(mTORC1)/wingless/integrated (Wnt)/β-catenin, the exosomal microRNA-31 (miR-31)/histone deacetylase 2 (HDAC2) signaling pathway, and the interaction of the extracellular matrix (ECM) and immune cells. Notably, HF, as a novel type of adenosine triphosphate (ATP)-dependent inhibitor that is often combined with prolyl transfer RNA synthetase (ProRS) and amino acid starvation therapy (AAS) to suppress the formation of ribosome, further exerts a significant effect on the tumor microenvironment (TME). Additionally, the combination of HF with other drugs or therapies obtained universal attention. Our results showed that HF has significant potential for clinical cancer treatment.

• Publication type
• Journal Article MeSH
• Review MeSH

In the last two decades, a school of thought emerged that perceives male reproductive health, testicular function, and sperm output as a sentry for general, somatic health. Large-scale epidemiologic studies have already linked the reduced sperm count to increased risk of chronic somatic disease (e.g., cancer, cardiovascular, neurological and bone diseases), yet most of these studies have not taken full advantage of advanced andrological analysis. Altered proteostasis, i.e., the disbalance between protein synthesis and turnover, is a common denominator of many diseases, including but not limited to cancer and neurodegenerative diseases. This chapter introduces the concept of cellular proteostasis as a measure of sperm structural and functional integrity and an endpoint of varied impacts on spermiogenesis and sperm maturation, including heritability, general health, lifestyle, and occupational and environmental reprotoxic exposure. Special consideration is given to small molecule protein modifiers, sperm-binding seminal plasma proteins, zinc-interacting proteins, and redox proteins responsible for the maintenance of protein structure and the protection of spermatozoa from oxidative damage. While the main focus is on human male infertility, serious consideration is given to relevant animal models, and in particular to male food animals with extensive records of fertility from artificial insemination services. Altogether, the proteostatic biomarker discovery and validation studies set the stage for the integration of proteomics of sperm proteostasis with genomic and high throughput phenomic approaches to benefit both human and animal reproductive medicine.

• MeSH
• Fertility * physiology   MeSH
• Proteostasis * physiology   MeSH
• Humans MeSH
• Infertility, Male * metabolism   genetics   pathology   physiopathology   MeSH
• Spermatogenesis * MeSH
• Spermatozoa * metabolism   pathology   physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Drug consumption rooms (DCRs) are harm reduction facilities providing safer and hygienic setting for supervised administration of drugs aimed at decreasing negative health and social consequences of drug use. The first DCR in Czechia was opened in September 2023 in city of Brno in a mobile form operating in a socially excluded area (SEA). A research project informed the implementation of the DCR. METHODS: A mixed methods design was applied in the following phases: desk review, research before and after the launch of the mobile DCR, and routine monitoring of programme performance. Two cross-sectional questionnaire surveys among PWUDs (n = 131 and 135), ethnographic observation, focus group (n = 19), interviews with PWUDs (n = 26 and 19), with personnel of addiction services and local officials (n = 16 and 12), and residents (n = 7 and 6) were performed prior to and after the launch of the DCR. Thematic analysis of qualitative data, descriptive and regression analyses of quantitative data were performed. RESULTS: There was a need and high willingness to use the DCR among potential clients. The significant predictors were opioid use (adjusted odds ratio, AOR = 3.4 in survey 1 and 3.9 in survey 2), drug injection in the last 30 days (AOR 4.3 in survey 1), being in the probationary period during the previous 30 days (AOR 10.0 in survey 1), witnessing an overdose in the past 30 days (AOR 8.5 in survey 2), HCV positivity ever in life (AOR 2.9 in survey 2), living in SEA (AOR 2.7 in survey 2) and Roma ethnicity (AOR 2.8 in survey 2). The beginnings of the DCR were relatively slow with low initial number of clients and drug administrations. However, with time, and programme adjustments following research results, the attendance at the facility has grown. CONCLUSIONS: Research was instrumental in shaping the DCR in Brno before and during its implementation. The DCR showed a potential to attract the most vulnerable PWUDs from SEA. Despite a slow start, the DCR has become an integral part of low-threshold services for PWUDs in Brno and has proven its feasibility in the Czech settings.

• MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Mobile Health Units * organization & administration   MeSH
• Substance-Related Disorders * MeSH
• Cross-Sectional Studies MeSH
• Surveys and Questionnaires MeSH
• Harm Reduction * MeSH
• Drug Users * statistics & numerical data   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

Aim: The aim of this integrative literature review was to identify and synthetize empowering educational actions (EEA) that can be taken by nurses to support the empowerment of patients with long-term health problems. Design: An integrative literature review. Methods: The review followed methodology by Whittemore and Knafl. Four databases (PubMed, Web of Science, CINAHL, Scopus) were searched between January 2000 and October 2023 for relevant studies published in English. After complimentary manual searches, the quality of the included studies (n = 9) was assessed independently by two researchers using a tool by Hawker et al. Data were analyzed using inductive content analysis. Results: Three main categories of nurses' actions were synthetized: supporting patients' knowledge and skills, supporting patients' well-being, and supporting trust-based relationships and collaboration. Conclusion: Empowering patient education (EPE) is essential in supporting patients with long-term health problems to manage their own health. Nurses use varied empowering educational actions as part of EPE. The review's results can be used to increase awareness and understanding of actions nurses can take to support empowerment of patients with long-term health problems as part of patient education both in clinical practice and nursing education.

The use of microfluidic sperm sorting (MFSS) systems in infertility treatment is increasing due to their practicality and ease of use. While often presented as highly effective, their efficacy in patients with varying sperm analysis results remains uncertain. In this study, we evaluated the effectiveness of MFSS compared with the swim-up (SU) technique in terms of oxygen radical levels and spermiogram parameters. Samples from each patient were processed using both methods, followed by assessments of sperm concentration, motility, morphology, DNA integrity, acrosomal status, and mitochondrial membrane potential. Participants were selected based on sperm analysis and categorized as normozoospermic (n = 40) or non-normozoospermic (n = 28). An analysis of separation techniques revealed no significant differences, except for a lower percentage of DNA-fragmented sperm in the MFSS group compared with SU within the non-normozoospermic cohort (SU: 10.0% vs. MFSS: 5.69%, p = 0.027). No differences were observed between SU and MFSS in normozoospermic men. The MFSS method is a simple technique, frequently used in laboratories, that yields good results but does not offer a substantial advantage over SU. The primary benefit of MFSS appears to be a significant reduction in the proportion of sperm with DNA fragmentation compared with SU in patients with abnormal sperm analysis results.

• MeSH
• Semen Analysis methods   MeSH
• Adult MeSH
• DNA Fragmentation MeSH
• Sperm Injections, Intracytoplasmic * methods   MeSH
• Humans MeSH
• Membrane Potential, Mitochondrial MeSH
• Microfluidics * methods   MeSH
• Sperm Motility * MeSH
• Infertility, Male therapy   MeSH
• Cell Separation * methods   MeSH
• Spermatozoa * cytology   metabolism   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH