OBJECTIVES: DNA repair proteins have emerged as potential predictors for immunotherapy response alongside PD-L1 expression, tumor-infiltrating lymphocytes (TILs) and tumor mutational burden. We analyzed expression of PD-L1, TILs count and expression of the homologous recombination (HR) protein RAD51, as potential prognostic factors in patients with resected non-small-cell lung carcinoma (NSCLC). MATERIALS AND METHODS: Discovery set included 96 NSCLC patients from the University Hospital Olomouc (Czech Republic) and a replication set included 1109 NSCLC patients from University Hospital Zurich (Switzerland). Tissue microarrays (TMAs) were stained using the automated staining platform Ventana Benchmark Ultra with antibodies against RAD51,CD3, CD8, CD68 and PD-L1. RESULTS: Loss of nuclear RAD51 protein was associated with high TILs (r=-0.25, p = 0.01) and PD-L1 status (10.6 vs. 2.4 %, p = 0.012) in patients receiving neoadjuvant chemo-/radiotherapy (CT/RT). In silico analysis from the TCGA data set showed a negative relationship between RAD51 mRNA expression and CD45 (r = ‒0.422, p < 0.0001), CD68 (r = ‒0.326, p < 0.001), CD3 (r = ‒0.266, p < 0.001) and CD8 (r = ‒0.102, p < 0.001). RAD51 low/PD-L1 high patients were clustered as separate entity in the replication set and in TCGA dataset. High TILs status was significantly associated with improved OS in the replication set (unadjusted HR = 0.57, 95 % CI 0.42-0.76, p < 0.001). Similar results have been seen for CD3, CD8 and CD68. CONCLUSIONS: In conclusion, RAD51 nuclear loss is weakly associated with increased TILs and high PD-L1 at the time of surgery in curatively resected NSCLC and after prior exposure to neoadjuvant chemo- or radiotherapy. Both high TILs and RAD51 nuclear loss were confirmed as independent prognostic factors in curatively resected NSCLC.

• MeSH
• antigeny CD274 genetika   MeSH
• lidé MeSH
• nádory plic * genetika   terapie   MeSH
• nemalobuněčný karcinom plic * genetika   terapie   MeSH
• oprava DNA MeSH
• prognóza MeSH
• rekombinasa Rad51 genetika   MeSH
• tumor infiltrující lymfocyty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Švýcarsko MeSH

Hodnocení zánětlivé celulizace (tumor infiltrujících lymfocytů – TIL) by u maligního melanomu mělo být standardní součástí bioptického vyšetření. Nejčastěji používaný způsob hodnocení podle Clarka však není optimální a je snaha o nalezení alternativního systému. V následujícím sdělení podáváme přehled možných přístupů zahrnujících pět různých způsobů hodnocení z barvení hematoxylin-eozinem včetně recentního návrhu sjednocené koncepce hodnocení TIL pro všechny solidní nádory. Diskutována je problematika metodiky, prognostického a prediktivního významu stanovení TIL a také význam imunohistochemické subtypizace zánětlivého infiltrátu.

The evaluation of inflammatory infiltrate (tumor infiltrating lymphocytes – TIL) should be a standard part of biopsy examination for malignant melanoma. Currently, the most commonly used assessment method according to Clark is not optimal and there have been attempts to find an alternative system. Here we present an overview of possible approaches involving five different evaluation methods based on hematoxylin-eosin staining, including the recent suggestion of unified TIL evaluation method for all solid tumors. The issue of methodology, prognostic and predictive significance of TIL determination as well as the importance of immunohistochemical subtyping of inflammatory infiltrate is discussed.

• MeSH
• biopsie MeSH
• imunohistochemie MeSH
• lidé MeSH
• melanom * diagnóza   imunologie   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• tumor infiltrující lymfocyty * imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Východiska: Triple negativní karcinomy prsu (triple-negative breast cancer - TNBC) jsou považovány za morfologicky a geneticky heterogenní skupinu karcinomů prsu charakterizovanou nízkou či nulovou expresí estrogenových i progesteronových receptorů, HER2/neu/ERBB2 proteinu, specifickým biologickým chováním a odpovědí na léčbu. Cílem naší práce bylo hodnocení intenzity lymfo/plazmocytární infiltrace (tumor-infiltrating lymphocytes/plasmocytes - TILs) v nádorovém parenchymu, jeho stromatu a v okolí invazivní fronty u časného karcinomu prsu bez předchozí chemoterapie a její korelace s morfologií nádoru, proliferační aktivitou, expresí Bcl-2 a dalšími vybranými klinicko-patologickými parametry. Materiál a metody: Z celkového počtu 3 544 karcinomů prsu diagnostikovaných na našem pracovišti mezi lety 2007 a 2017 bylo 413 TNBC (11,65 %). Z toho jsme získali pouze 61 případů, které byly primárně léčeny chirurgicky a které neměly morfologii poškozenou chemoterapií. U nich jsme korelovali intenzitu infiltrace TILs s morfologií, expresí Bcl-2 proteinu, proliferační aktivitou měřenou expresí Ki-67, věkem pacientek, stupněm diferenciace (grade) a výskytem metastáz. Výsledky: V našem souboru TNBC dominovaly invazivní karcinomy NST (no special type) s medulárními rysy (80,32 %), které formovaly poměrně dobře ohraničené léze průměrné velikosti 13,4 mm (rozmezí od 5 do 20 mm, medián 15 mm) s centrální nekrózou či fibrózou, často s vřetenobuněčnou transformací a/nebo alespoň v malém úseku s ložisky podobnými apokrinní diferenciaci a variabilně intenzivním TILs. V souboru se však vyskytly i nádory, jejichž morfologie není typická pro TNBC. Prokázali jsme statisticky významnou pozitivní korelaci infiltrace TILs s premenopauzálním stavem (p = 0,003), expresí Ki-67 (p = 0,015), gradem (p = 0,002), hraniční pozitivní korelaci s velikostí nádorů (p = 0,065) a statisticky významnou negativní korelaci s expresí proteinu Bcl-2 (p = 0,035). U mladších žen (do 50 let) s velikostí nádorů do 20 mm (pT1a-pT1c) jsme zaznamenali nižší počet případů s metastatickým postižením lymfatických uzlin (p = 0,001). Závěr: Intenzita a lokalizace TILs infiltrace vyhodnocovaná v kontextu morfologických změn a dalších klinicko-patologických znaků u terapií neovlivněných TNBC může mít prognostický význam a poskytnout podklad pro plánování efektivnější terapie.

Background: Triple-negative breast cancers (TNBCs) are considered a morphologically heterogeneous group of breast carcinomas characterized by the absence or low protein expression of hormone receptors and HER2/neu/ERBB2 with a specific biological behavior and therapeutic response. This study aimed to evaluate correlations of the density of tumor-infiltrating lymphocytes/plasmocytes (TILs) in the tumor parenchyma, stroma, and invasive margins with tumor morphology, the proliferation rate, Bcl-2 expression, and selected clinical and pathological parameters in early breast cancer patients prior to mastectomy who had not received initial chemotherapy. Materials and methods: Samples of 3,544 breast cancer patients investigated in our department between 2007 and 2017 were re-examined. In total, 413 (11.65%) patients were diagnosed with TNBC. Only 61 cases did not undergo neoadjuvant therapy prior to mastectomy. Correlations between the density of TILs and tumor morphology, Bcl-2 expression, proliferative activity measured by Ki-67, patient age at diagnosis, tumor grade, and metastases were investigated. Results: The samples were predominantly relatively well-localized invasive carcinomas of no special type with medullary features (80.32%) that measured on average 13.4 mm (range 5-20 mm, median 15 mm) and exhibited central necrosis or fibrosis, a tendency to undergo spindle cell and/or apocrine-like differentiation, and intensive infiltration of TILs. There were significant positive correlations between TILs and premenopausal status (p=0.003), Ki-67 expression (p=0.015), and tumor grade (p=0.002), a marginal positive correlation between TILs and tumor size (p=0.065), and a significant negative correlation between TILs and Bcl-2 expression (p=0.035). In younger patients (< 50 years) with tumor size less than or equal to 20 mm (pT1a-pT1c) we recorded a lower number of women with metastatic lymph node involvement (p=0.001). Conclusion: The density and location of TILs in non-therapeutically influenced TNBCs, evaluated in the context of morphological changes and other clinicopathological parameters, may have prognostic significance and assist effective therapy planning.

• MeSH
• dospělí MeSH
• geny bcl-2 MeSH
• lidé středního věku MeSH
• lidé MeSH
• mastektomie MeSH
• nádory prsu patologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• triple-negativní karcinom prsu * patologie   MeSH
• tumor infiltrující lymfocyty MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: We aimed to assess the prognostic value of tumor infiltrating lymphocytes (TILs) in patients with bladder cancer (BC) after radical cystectomy (RC). MATERIALS AND METHODS: We searched Pubmed, Web of Science and Scopus in April 2022 to identify studies assessing the prognostic value of TILs, including a subset of lymphocytes (eg, CD3, CD8, FOXP3), after RC. The endpoints were overall survival and recurrent free survival. Subgroup analyses were performed based on the evaluation method for TILs (ie, CD3, CD8, FOXP3, HE staining). RESULTS: Overall, 9 studies comprising 1413 patients were included in this meta-analysis. The meta-analysis revealed that elevated expressions of TILs were significantly associated with favorable OS (pooled hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.51-0.83) and RFS (pooled HR: 0.48, 95% CI: 0.35-0.64). In subgroup analyses, high CD8+ TILs were also associated with favorable OS (HR: 0.51, 95% CI: 0.33-0.80) and RFS (pooled HR: 0.53, 95% CI: 0.36-0.76). Among 3 studies comprising 146 patients, high intratumoral TILs were significantly associated with favorable OS (pooled HR: 0.34, 95% CI: 0.19-0.60). CONCLUSION: TILs are useful prognostic markers in patients treated with RC for BC. Although the prognostic value of TILs is varied, depending on the subset and infiltration site, CD8+ TILs and intratumoral TILs are associated with oncologic outcomes. Further studies are warranted to explicate the predictive value of TILs on the response to perioperative systemic therapy to help clinical decision-making in patients with BC.

• MeSH
• cystektomie MeSH
• forkhead transkripční faktory metabolismus   MeSH
• lidé MeSH
• nádory močového měchýře * patologie   MeSH
• prognóza MeSH
• tumor infiltrující lymfocyty * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• systematický přehled MeSH

This is an overview of current problematics regarding the role of tumor infiltrating lymphocytes (TILs) in malignant melanomas. Various and often conflicting data have been published, correlating tumor type, stage, prognosis, as well as sex and age of patients. This is partly due to heterogeneity in scaling systems and unstandardized TILs grading but also due to changes of tumor-host interactions. Melanomas are an immunologically heterogeneous group with variability of TILs, where distinct gene expression patterns were found in tumors with absent, and/or non- brisk TIL grade versus brisk TIL grade. However, the presence of TILs alone appears to be inadequate for implicating them as immunologically functional. Further characterisation of TIL phenotype and function is warranted. This especially concerns, evaluation of TILs of the suppressor phenotype but rather than as a prognostic factor, more for prediction of targeted immunotherapy.

• MeSH
• lidé MeSH
• melanom etiologie   patologie   MeSH
• nádory kůže etiologie   patologie   MeSH
• tumor infiltrující lymfocyty fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND/AIM: Tumour-infiltrating lymphocytes (TILs) and Granzyme B play crucial roles in immune reactions against colorectal carcinoma (CRCa). The inhibitor of Granzyme B is Serpin B9. The aim of this study was to evaluate the effect of immunohistological parameters of TILs on the prognosis of CRCa and presence of lymph node metastasis. PATIENTS AND METHODS: A total of 152 patients who underwent surgery for CRCa were analyzed, including 63 patients in cohort stage II, according to the Union for International Cancer Control (UICC), and 89 patients in cohort UICC stage III. The TIL pattern was classified as peritumoural (PTL), intratumoural (ITL), intrastromal (ISL) or Crohn-like, and immunohistological staining of TIL and cancer cells was also performed. RESULTS: A significantly higher density of CD8+ and CD4+ TILs was observed in the UICC II group, and significantly higher densities of CD4+ TILs were observed in the UICC II group in all distinguished patterns. In the same cohort, higher numbers of CD57+ cells and FoxP3+ TILs and Granzyme B levels were observed. In cohort UICC III, there was a higher density of ISL, PTL CD8+, CD25+ TILs and cancer cells showed staining for Serpin B9. CD57, Granzyme B and CD8 were demonstrated as positive prognostic factors of overall survival, and CD57 and CD4+ TILs were demonstrated as positive prognostic factors of recurrence. CONCLUSION: TILs and CD57 are promising prognostic factors of CRCa. The association of Serpin B9 with lymph node metastasis reveals a potential mechanism for tumour resistance to immune reaction.

• MeSH
• kolorektální nádory imunologie   patologie   MeSH
• lidé MeSH
• lymfatické metastázy imunologie   patologie   MeSH
• nádorové biomarkery imunologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tumor infiltrující lymfocyty imunologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Primary cilium (PC) is considered to be a functional homologue of the immune synapse. Microtubule structures, PC of cancer associated fibroblasts and immune synapses between cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) and cancer cells, are regularly found in varying amounts in the microenvironment of solid tumors. The purpose of this study was to find out the potential association and combined prognostic significance of the frequency of PC, PD-1 and CD8+ TILs in patients with intestinal cancer. METHODS: The frequency of PC, programmed cell death protein-1 receptor (PD-1) expression and the frequency of stromal and intraepithelial CD8+TILs were evaluated in samples of colorectal adenocarcinoma (32 patiens) and small bowel cancer (8 patients). RESULTS: The median frequency of PC was 0.25%. The expression of PD1 was <5% in 34 patients, 5-25% in 5 patients and 26-50% in 1 patient. The frequency of stromal CD8+ TILs was negative in 3 patients, <25% in 26, 26-50% in 10 and >50% in 1 patient, respectively. Intraepithelial CD8+ TILs were not detectable in 14, <25% in 24 and 26-50% in 2 patients, respectively. Statistically, the frequency of PC and PD-1 positivity were significantly associated (p=0.004). An association between the PC frequency and intraepithelial CD8+ TILs was of borderline statistical significance (p=0.059). An index combining the frequency of PC and stromal CD8+ TILs, but not the combination of frequency of PC and intraepithelial CD8+ TILs, was of borderline prognostic significance (p=0.067). CONCLUSIONS: The present study provides the first data on the potential association and combined prognostic significance of frequency of PC, PD-1 and CD8+ TILs in patients with intestinal cancer.

• MeSH
• antigeny CD279 metabolismus   MeSH
• CD8-pozitivní T-lymfocyty metabolismus   MeSH
• cilie patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• střevní nádory genetika   metabolismus   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Summary: Introduction: When checking tumour growth, a number of observations indicate that the immune system plays a significant role in patients with renal cell carcinoma (RCC). Infiltration by lymphocytes (tumour infiltrating lymphocytes, TILs) is more prevalent in RCC than any other tumours. T lymphocytes are the dominant population of TIL cells. Views concerning the role of T lymphocytic subpopulations, B lymphocytes and NK cells in an anti-tumour response are not established. Aim: The aim is to determine the phenotype and activation of T and B lymphocytic subpopulations and NK cells and to compare their representation in tumour stroma and peripheral blood lymphocytes (PBL) in patients with RCC. Material and methods: Samples of peripheral blood taken from the cubital and renal veins and tumour stroma cells were obtained from 44 patients in the course of their surgeries carried out due to primary RCC. TILs were isolated from mechanically disintegrated tumour tissue. Immunophenotype multiparametric analysis of PBL and TILs was carried out. Their surface and activation characteristics were determined by means of flow cytometer. Results: CD3+ T lymphocytes (69.7 %) were the main population of TILs. The number of CD3+/CD8+ T lymphocytes was significantly higher in TILs, 42.6 % (p< 0.01), while CD4+ T lymphocytes were the majority population in peripheral blood, 41.35 % (p < 0.001). The representation of CD3+/69+ T lymphocytes was significantly higher in TILs, 32.9 %, compared to PBL (p<0.001). On the contrary, the numbers of CD3+/CD25+, CD8+/57+ and CD4+/RA+ (naive CD4+ T lymphocytes) were higher in PBL (p<0.001). The differences in representation of (CD3–/16+56+) NK cells and CD3+/DR+ T cells in TILs and PBL were not significant. Conclusion: The above-mentioned results prove that the characteristics and intensity of anti-tumour responses are different in compared compartments (tumour/PBL). CD3+/CD8+ T lymphocytes are the dominant lymphocytic population of TILs. The knowledge of the phenotype and functions of effector cells, which are responsible for anti-tumour response, are the basic precondition for understanding the anti-tumour immune response and the cause of its failure.

• MeSH
• B-lymfocyty cytologie   imunologie   MeSH
• buňky NK cytologie   imunologie   MeSH
• CD4-pozitivní T-lymfocyty cytologie   imunologie   MeSH
• CD8-pozitivní T-lymfocyty cytologie   imunologie   MeSH
• finanční podpora výzkumu jako téma MeSH
• karcinom z renálních buněk genetika   imunologie   krev   MeSH
• lidé MeSH
• průtoková cytometrie metody   využití   MeSH
• T-lymfocyty cytologie   imunologie   MeSH
• tumor infiltrující lymfocyty cytologie   imunologie   MeSH
• Check Tag
• lidé MeSH

Východiska: Cílem této studie je retrospektivně zhodnotit imunomodulační účinek před­operační radiochemoterapie lokálně pokročilého karcinomu rekta imunohistochemickým vyšetřením hustoty CD8+ tumor infiltrujících lymfocytů (TIL) v endobiopsii před předoperační radiochemoterapií a u stejných pacientů v chirurgickém resekátu po předoperační radiochemoterapii. Pacienti a metody: Do studie bylo zařazeno 53 pacientů s lokálně pokročilým adenokarcinomem rekta léčených předoperační radiochemoterapií. Výsledky: Medián hustoty CD8+ TIL v endobiopsii před radiochemoterapií činil 12 (1–232) CD8+ TIL a v chirurgickém resekátu po radiochemoterapii 18 (1–319) CD8+ TIL. V průběhu předoperační radiochemoterapie došlo u 30 (57 %) pacientů k nárůstu hustoty CD8+ TIL, u 18 (34 %) pacientů došlo k poklesu, u jednoho pacienta zůstala hustota CD8+ TIL zachována, u čtyř pacientů nebylo možné změnu hustoty CD8+ TIL hodnotit. Pacienti s nárůstem CD8+ TIL po radiochemoterapii měli statisticky nesignifikantní 2,5krát delší medián celkového přežití. Závěr: V hodnoceném souboru nebyl prokázán prediktivní ani prognostický význam hustoty CD8+ TIL u pacientů léčených předoperační radiochemoterapií pro lokálně pokročilý adenokarcinom rekta, což může být způsobeno limitovaným počtem pacientů.

Background: The goal of this study is to examine the effect of neoadjuvant radiochemotherapy on the density of CD8+ tumor infiltrating lymphocytes (TILs) in endoscopical biopsies and resection specimens from patients with rectal adenocarcinoma before and after therapy. Patients and Methods: In total, 53 patients with locally advanced rectal cancer were studied. Results: The median density of CD8+ TILs in pretreatment biopsies was 12 (1–232) and that in surgical specimens after radiochemotherapy was 18 (1–319). During radiochemotherapy, the density of CD8+ TILs increased in 30 patients (57%), decreased in 18 (34%), and did not change in one. It was not possible to assess the dynamics of CD8+ TILs density in four patients. The increased density of CD8+ TILs after radiochemotherapy was associated with a median survival rate 2.5 times longer than that associated with no increase in density. Conclusion: In the present study, the density of CD8+ TILs in endoscopical biopsies before radiochemotherapy, the density in resection specimens after radiochemotherapy, or in changes in the density after radiochemotherapy showed no predictive or prognostic significance. However, studying a larger number of patients may show that CD8+ TILs density is of predictive or prognostic significance.

• MeSH
• adenokarcinom chirurgie   radioterapie   MeSH
• CD8-pozitivní T-lymfocyty * účinky záření   MeSH
• chemoradioterapie * využití   MeSH
• dávka záření MeSH
• dospělí MeSH
• imunohistochemie využití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory rekta * chirurgie   radioterapie   MeSH
• prediktivní hodnota testů MeSH
• předoperační péče MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• výsledky a postupy - zhodnocení (zdravotní péče) MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: There is a growing importance of loneliness measurement through valid and reliable instruments. However, to establish valid and reliable measures, there is a need to explore their psychometric properties in different research settings and language environments. For this reason, this study aimed to validate the Three Item Loneliness Scale (TILS) in the Czech Republic within a Slavonic language environment. METHODS: A sample of Czech adults (n = 3236) was used consisting primarily of university students. We utilized Classical Test Theory to assess TILS internal consistency, temporal stability, and factor structure. Item Response Theory (IRT) was used to estimate Differential Item Functioning (DIF), the discrimination and difficulty of the TILS items and to estimate the measurement precision of the whole scale. Construct validity was explored through the Spearman correlation coefficient using personality traits, depression, and anxiety. RESULTS: The results showed satisfactory reliability and validity of the TILS in the Czech Republic. The scale's internal consistency and temporal stability were found to be satisfactory (Cronbach's α = 0.81, McDonald's ω = 0.82, ICC = 0.71). The parallel analysis supported the unidimensionality of the TILS. The IRT results indicated that the highest measurement precision was reached in individuals with lower and above-average levels of loneliness. Significant correlations between the TILS scores, anxiety, depression, and personality traits supported the construct validity of the scale. Although the DIF analysis identified statistically significant differences in responses to items TILS_2 and TILS_3 based on education level and employment status (with no significant differences observed for TILS_1), the effect sizes of these differences were small. This indicates that, despite statistical significance, the practical impact on the scale's validity across these groups is minimal. CONCLUSIONS: The validated TILS provides a reliable and valid tool for assessing loneliness in the Czech Republic. Its brevity makes it a practical option for researchers and clinicians seeking to measure loneliness time-efficiently. Future studies should explore how adding new items could increase the measurement precision of the TILS.

• MeSH
• deprese psychologie   diagnóza   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• osamocení * psychologie   MeSH
• průzkumy a dotazníky normy   MeSH
• psychometrie * MeSH
• reprodukovatelnost výsledků MeSH
• úzkost psychologie   diagnóza   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH