PURPOSE OF REVIEW: Upper tract urothelial carcinoma (UTUC) is a rare malignancy posing significant diagnostic and management challenges. This review provides an overview of the evidence supporting various imaging modalities and offers insights into future innovations in UTUC imaging. RECENT FINDINGS: With the growing use of advancements in computed tomography (CT) technologies for both staging and follow-up of UTUC patients, continuous innovations aim to enhance performance and minimize the risk of excessive exposure to ionizing radiation and iodinated contrast medium. In patients unable to undergo CT, magnetic resonance imaging serves as an alternative imaging modality, though its sensitivity is lower than CT. Positron emission tomography, particularly with innovative radiotracers and theranostics, has the potential to significantly advance precision medicine in UTUC. Endoscopic imaging techniques including advanced modalities seem to be promising in improved visualization and diagnostic accuracy, however, evidence remains scarce. Radiomics and radiogenomics present emerging tools for noninvasive tumor characterization and prognosis. SUMMARY: The landscape of imaging for UTUC is rapidly evolving, with significant advancements across various modalities promising improved diagnostic accuracy, patient outcomes, and safety.
- MeSH
- Carcinoma, Transitional Cell * diagnosis diagnostic imaging therapy pathology MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Kidney Neoplasms diagnostic imaging therapy diagnosis pathology MeSH
- Ureteral Neoplasms diagnostic imaging diagnosis therapy pathology MeSH
- Tomography, X-Ray Computed methods MeSH
- Positron-Emission Tomography methods MeSH
- Neoplasm Staging MeSH
- Urologic Neoplasms diagnosis diagnostic imaging therapy pathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Cancer is a heterogeneous disease, which contributes to its rapid progression and therapeutic failure. Besides interpatient tumor heterogeneity, tumors within a single patient can present with a heterogeneous mix of genetically and phenotypically distinct subclones. These unique subclones can significantly impact the traits of cancer. With the plasticity that intratumoral heterogeneity provides, cancers can easily adapt to changes in their microenvironment and therapeutic exposure. Indeed, tumor cells dynamically shift between a more differentiated, rapidly proliferating state with limited tumorigenic potential and a cancer stem cell (CSC)-like state that resembles undifferentiated cellular precursors and is associated with high tumorigenicity. In this context, CSCs are functionally located at the apex of the tumor hierarchy, contributing to the initiation, maintenance, and progression of tumors, as they also represent the subpopulation of tumor cells most resistant to conventional anti-cancer therapies. Although the CSC model is well established, it is constantly evolving and being reshaped by advancing knowledge on the roles of CSCs in different cancer types. Here, we review the current evidence of how CSCs play a pivotal role in providing the many traits of aggressive tumors while simultaneously evading immunosurveillance and anti-cancer therapy in several cancer types. We discuss the key traits and characteristics of CSCs to provide updated insights into CSC biology and highlight its implications for therapeutic development and improved treatment of aggressive cancers.
- MeSH
- Humans MeSH
- Neoplastic Stem Cells * pathology metabolism MeSH
- Tumor Microenvironment * MeSH
- Neoplasms * pathology genetics metabolism therapy MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
OBJECTIVES: The development of External Quality Assessment Schemes (EQAS) for clinical flow cytometry (FCM) is challenging in the context of rare (immunological) diseases. Here, we introduce a novel EQAS monitoring the primary immunodeficiency Orientation Tube (PIDOT), developed by EuroFlow, in both a 'wet' and 'dry' format. This EQAS provides feedback on the quality of individual laboratories (i.e., accuracy, reproducibility and result interpretation), while eliminating the need for sample distribution. METHODS: In the wet format, marker staining intensities (MedFIs) within landmark cell populations in PIDOT analysis performed on locally collected healthy control (HC) samples, were compared to EQAS targets. In the dry format, participants analyzed centrally distributed PIDOT flow cytometry data (n=10). RESULTS: We report the results of six EQAS rounds across 20 laboratories in 11 countries. The wet format (212 HC samples) demonstrated consistent technical performance among laboratories (median %rCV on MedFIs=34.5 %; average failure rate 17.3 %) and showed improvement upon repeated participation. The dry format demonstrated effective proficiency of participants in cell count enumeration (range %rCVs 3.1-7.1 % for the major lymphoid subsets), and in identifying lymphoid abnormalities (79.3 % alignment with reference). CONCLUSIONS: The PIDOT-EQAS allows laboratories, adhering to the standardized EuroFlow approach, to monitor interlaboratory variations without the need for sample distribution, and provides them educational support to recognize rare clinically relevant immunophenotypic patterns of primary immunodeficiencies (PID). This EQAS contributes to quality improvement of PID diagnostics and can serve as an example for future flow cytometry EQAS in the context of rare diseases.
PURPOSE: The aim of this study was to develop a simple, robust, and easy-to-use calibration procedure for correcting misalignments in rosette MRI k-space sampling, with the objective of producing images with minimal artifacts. METHODS: Quick automatic calibration scans were proposed for the beginning of the measurement to collect information on the time course of the rosette acquisition trajectory. A two-parameter model was devised to match the measured time-varying readout gradient delays and approximate the actual rosette sampling trajectory. The proposed calibration approach was implemented, and performance assessment was conducted on both phantoms and human subjects. RESULTS: The fidelity of phantom and in vivo images exhibited significant improvement compared with uncorrected rosette data. The two-parameter calibration approach also demonstrated enhanced precision and reliability, as evidenced by quantitative T2*$$ {\mathrm{T}}_2^{\ast } $$ relaxometry analyses. CONCLUSION: Adequate correction of data sampling is a crucial step in rosette MRI. The presented experimental results underscore the robustness, ease of implementation, and suitability for routine experimental use of the proposed two-parameter rosette trajectory calibration approach.
- MeSH
- Algorithms * MeSH
- Artifacts * MeSH
- Phantoms, Imaging * MeSH
- Calibration MeSH
- Humans MeSH
- Magnetic Resonance Imaging * methods MeSH
- Brain diagnostic imaging MeSH
- Image Processing, Computer-Assisted * methods MeSH
- Reproducibility of Results MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Increased lung cancer risks for low socioeconomic status (SES) groups are only partially attributable to smoking habits. Little effort has been made to investigate the persistent risks related to low SES by quantification of potential biases. METHODS: Based on 12 case-control studies, including 18 centers of the international SYNERGY project (16,550 cases, 20,147 controls), we estimated controlled direct effects (CDE) of SES on lung cancer via multiple logistic regression, adjusted for age, study center, and smoking habits and stratified by sex. We conducted mediation analysis by inverse odds ratio weighting to estimate natural direct effects and natural indirect effects via smoking habits. We considered misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by genetic risk, both separately and by multiple quantitative bias analyses, using bootstrap to create 95% simulation intervals (SI). RESULTS: Mediation analysis of lung cancer risks for SES estimated mean proportions of 43% in men and 33% in women attributable to smoking. Bias analyses decreased the direct effects of SES on lung cancer, with selection bias showing the strongest reduction in lung cancer risk in the multiple bias analysis. Lung cancer risks remained increased for lower SES groups, with higher risks in men (fourth vs. first [highest] SES quartile: CDE, 1.50 [SI, 1.32, 1.69]) than women (CDE: 1.20 [SI: 1.01, 1.45]). Natural direct effects were similar to CDE, particularly in men. CONCLUSIONS: Bias adjustment lowered direct lung cancer risk estimates of lower SES groups. However, risks for low SES remained elevated, likely attributable to occupational hazards or other environmental exposures.
- MeSH
- Mediation Analysis * MeSH
- Adult MeSH
- Smoking * epidemiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Logistic Models MeSH
- Lung Neoplasms * epidemiology MeSH
- Odds Ratio MeSH
- Risk Factors MeSH
- Aged MeSH
- Social Class * MeSH
- Case-Control Studies MeSH
- Bias * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Brucellosis is one of the most important zoonoses worldwide, primarily affecting livestock but also posing a serious threat to public health. The major Brucella species are known to cause a feverish disease in humans with various clinical signs. These classical Brucella species are (re-)emerging, but also novel strains and species, some of them transmitted from rodents, can be associated with human infections. As a result of our review on rodent-borne brucellosis, we emphasise the need for more comprehensive surveillance of Brucella and especially Brucella microti in rodent populations and call for further research targeting the ecological persistence of rodent-associated Brucella species in the environment, their epizootic role in wild rodents and their virulence and pathogenicity for wildlife.
- MeSH
- Brucella * isolation & purification MeSH
- Brucellosis * epidemiology veterinary microbiology transmission MeSH
- Rodentia * microbiology MeSH
- Humans MeSH
- Public Health * MeSH
- Zoonoses * MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Mitochondria are vital organelles with their own DNA (mtDNA). mtDNA is circular and composed of heavy and light chains that are structurally more accessible than nuclear DNA (nDNA). While nDNA is typically diploid, the number of mtDNA copies per cell is higher and varies considerably during development and between tissues. Compared with nDNA, mtDNA is more prone to damage that is positively linked to many diseases, including cancer. Similar to nDNA, mtDNA undergoes repair processes, although these mechanisms are less well understood. In this review, we discuss the various forms of mtDNA damage and repair and their association with cancer initiation and progression. We also propose horizontal mitochondrial transfer as a novel mechanism for replacing damaged mtDNA.
- MeSH
- Humans MeSH
- DNA, Mitochondrial * genetics MeSH
- Mitochondria * genetics metabolism MeSH
- Neoplasms * genetics pathology MeSH
- DNA Repair * MeSH
- DNA Damage * genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
While there is substantial research on what people want in their romantic and sexual partners, much of this work focuses on WEIRD, youthful samples, fails to consider the role of undesirable characteristics (i.e., things people do not want in partners) at all, or in conjunction with desirable characteristics (i.e., things people do want in partners), and may be overly reliant on psychometric approaches to pivotal variables in mating psychology like mate value and sociosexuality. In a nationally representative (online) sample of 2280 people from Czechia (aged between 18 and 50 years old), we examined linear and quadratic age, education, and self-perceived mate value (desirability) effects on the desired levels in mate choice of eight undesirable and seven desirable characteristics in men and women in relation to ostensible metrics of mate value. Self-perceived mate value alone explained little variance (men 1%, women 2%), while all mate value and mating strategy indicators together explained little variance of mate preferences and aversions (men 3%, women 5%). Desirable characteristics were better explained by mate value than undesirable ones. Our results are in line with evolutionary predictions suggesting that women are more demanding. Also, more qualities to offer correlate with more expectations in a partner.
- MeSH
- Adult MeSH
- Interpersonal Relations MeSH
- Middle Aged MeSH
- Humans MeSH
- Marriage psychology MeSH
- Adolescent MeSH
- Young Adult MeSH
- Surveys and Questionnaires MeSH
- Self Concept MeSH
- Sexual Behavior psychology MeSH
- Sexual Partners * psychology MeSH
- Choice Behavior MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
BACKGROUND AND OBJECTIVE: Biparametric magnetic resonance imaging (bpMRI), excluding dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), is a potential replacement for multiparametric MRI (mpMRI) in diagnosing clinically significant prostate cancer (csPCa). An extensive international multireader multicase observer study was conducted to assess the noninferiority of bpMRI to mpMRI in csPCa diagnosis. METHODS: An observer study was conducted with 400 mpMRI examinations from four European centers, excluding examinations with prior prostate treatment or csPCa (Gleason grade [GG] ≥2) findings. Readers assessed bpMRI and mpMRI sequentially, assigning lesion-specific Prostate Imaging Reporting and Data System (PI-RADS) scores (3-5) and a patient-level suspicion score (0-100). The noninferiority of patient-level bpMRI versus mpMRI csPCa diagnosis was evaluated using the area under the receiver operating curve (AUROC) alongside the sensitivity and specificity at PI-RADS ≥3 with a 5% margin. The secondary outcomes included insignificant prostate cancer (GG1) diagnosis, diagnostic evaluations at alternative risk thresholds, decision curve analyses (DCAs), and subgroup analyses considering reader expertise. Histopathology and ≥3 yr of follow-up were used for the reference standard. KEY FINDINGS AND LIMITATIONS: Sixty-two readers (45 centers and 20 countries) participated. The prevalence of csPCa was 33% (133/400); bpMRI and mpMRI showed similar AUROC values of 0.853 (95% confidence interval [CI], 0.819-0.887) and 0.859 (95% CI, 0.826-0.893), respectively, with a noninferior difference of -0.6% (95% CI, -1.2% to 0.1%, p < 0.001). At PI-RADS ≥3, bpMRI and mpMRI had sensitivities of 88.6% (95% CI, 84.8-92.3%) and 89.4% (95% CI, 85.8-93.1%), respectively, with a noninferior difference of -0.9% (95% CI, -1.7% to 0.0%, p < 0.001), and specificities of 58.6% (95% CI, 52.3-63.1%) and 57.7% (95% CI, 52.3-63.1%), respectively, with a noninferior difference of 0.9% (95% CI, 0.0-1.8%, p < 0.001). At alternative risk thresholds, mpMRI increased sensitivity at the expense of reduced specificity. DCA demonstrated the highest net benefit for an mpMRI pathway in cancer-averse scenarios, whereas a bpMRI pathway showed greater benefit for biopsy-averse scenarios. A subgroup analysis indicated limited additional benefit of DCE MRI for nonexperts. Limitations included that biopsies were conducted based on mpMRI imaging, and reading was performed in a sequential order. CONCLUSIONS AND CLINICAL IMPLICATIONS: It has been found that bpMRI is noninferior to mpMRI in csPCa diagnosis at AUROC, along with the sensitivity and specificity at PI-RADS ≥3, showing its value in individuals without prior csPCa findings and prostate treatment. Additional randomized prospective studies are required to investigate the generalizability of outcomes.
- MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Multiparametric Magnetic Resonance Imaging * MeSH
- Prostatic Neoplasms * diagnostic imaging pathology MeSH
- Observer Variation MeSH
- Aged MeSH
- Neoplasm Grading MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Comparative Study MeSH
- Geographicals
- Europe MeSH
BACKGROUND: Suicides are a major public health problem with serious consequences for societies. AIM: To compare epidemiological patterns and trends of suicides in the Czech Republic, Slovakia, Hungary, and Poland in 1990-2019, and analyze them in the European and global context. METHODS: A trend analysis was conducted in Czech Republic, Slovakia, Hungary, Poland, in Western Europe and on global level for 1990-2019. All data were obtained from the Global Burden of Diseases study 2019. Numbers and age-standardized rates of deaths and Years of Life Lost (YLL) due to suicides were analyzed, stratified by sex and age (0-14 years old, 15-49 years old, 50-69 years old, 70+ years). RESULTS: In 2019, 759,028 suicides occurred globally, 17,408 (2.3%) in Central Europe. The proportion of males was substantially larger, compared to the global and Western European levels (e.g., 82 vs. 69 and 75%, respectively). The highest rates of suicide were in Hungary (19.7 per 100,000), lowest in Slovakia (12.8); the rate in Central Europe was higher than the global rate (15.2 vs. 9.8), and the rate in Western Europe (11.4). A steady decline of rates was observed in all countries, particularly in Hungary. In Czech Republic we found an increasing relative importance of suicides among people 70 years and older. CONCLUSIONS: Death rates due to suicides have been declining in the analyzed countries, but some characteristics and trends when compared to global and regional estimates, such as substantially higher proportion of male suicides or high death rates among the elderly warrant specifically tailored preventative action coordinated by governments with community involvement.
- MeSH
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Suicide * statistics & numerical data trends MeSH
- Aged MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
- Europe MeSH
- Hungary MeSH
- Poland MeSH
- Slovakia MeSH
