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PURPOSE OF REVIEW: Men face distinctive health-related challenges as a result of biological, behavioral, and sociocultural factors. In addition, the modern healthcare system does not offer men equal opportunities and options to ensure sex-specific access and delivery to health services. Men's health concerns are, indeed, often not addressed or even forgotten. In this review, we wanted to assess the impact of biology and sociocultural effects on sex-specific life-expectancy. RECENT FINDINGS: Globally, men have a shorter life expectancy than women. With a 5.8 years gender gap in the USA and 5.4 in the EU-27 (both in 2022). Cardiovascular disease, cancer, and accidents continue to represent the primary causes of mortality for both genders with all having disproportional preponderance in men. In recent years, there has been a notable decline in age-adjusted mortality rates related to cancer, while there has been an increase in deaths from accidental and intentional self-harm. Moreover, in the United States, men are more likely than women to develop and die from nonsex-specific cancers. As a result, men's poor health affects productivity, absenteeism, and employment. SUMMARY: The status of men in healthcare is complex. It is rooted in history, culture, and institutions. To address disparities, we need a comprehensive approach that includes policy reforms, sociocultural changes, and a fair and equitable public discourse. Grassroots and top-down strategies are needed to ensure a value-based societal healthcare system acknowledging the unique health needs of men.
- MeSH
- disparity zdravotní péče statistika a číselné údaje MeSH
- disparity zdravotního stavu MeSH
- dostupnost zdravotnických služeb statistika a číselné údaje MeSH
- lidé MeSH
- naděje dožití * MeSH
- poskytování zdravotní péče statistika a číselné údaje MeSH
- rovnost ve zdraví MeSH
- sexuální faktory MeSH
- zdraví mužů * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Spojené státy americké MeSH
BACKGROUND AND OBJECTIVES: N-acetyl-l-leucine (NALL) has been established to improve the neurologic manifestations of Niemann-Pick disease type C (NPC) after 12 weeks in a placebo-controlled trial. In the open-label extension phase (EP) follow-up, data were obtained after 12 and 18 months to evaluate the long-term effects of NALL for NPC. METHODS: This is an ongoing, multinational, multicenter EP. Patients with a genetic diagnosis of NPC aged 4 years or older who completed the placebo-controlled trial were eligible to continue in the EP and receive orally administered NALL 2-3 times per day in 3 tiers of weight-based dosing. The primary end point is the modified 5-domain NPC Clinical Severity Scale (NPC-CSS) (range 0-25 points; lower score representing better neurologic status); data from the EP cohort are compared with the expected annual trajectory of decline (i.e., disease progression) established in natural history studies. Analyses are also performed on exploratory end points, including the 15-domain and 4-domain NPC-CSSs and the Scale for Assessment and Rating of Ataxia (SARA). RESULTS: Fifty-three patients aged 5-67 years (45.3% female, 54.7% male) were enrolled in the EP. After 12 months, the mean (±SD) change from baseline on the 5-domain NPC-CSS was -0.27 (±2.42) with NALL vs +1.5 (±3.16) in the historical cohort (95% CI -3.05 to -0.48; p = 0.009), corresponding to a 118% reduction in annual disease progression. After 18 months, the mean (±SD) change was +0.05 (±2.95) with NALL vs +2.25 (±4.74) in the historical cohort (95% CI -4.06 to -0.35; p = 0.023). The 15-domain and 4-domain NPC-CSSs were consistent with the 5-domain NPC-CSS. The improvements in neurologic manifestations demonstrated in the placebo-controlled trial on the primary SARA end point were sustained over the long-term follow-up. NALL was well tolerated, and no treatment-related adverse events or serious reactions occurred. DISCUSSION: Treatment with NALL was associated with a significant reduction in NPC disease progression after 12 and 18 months, demonstrating a disease-modifying, neuroprotective effect. TRIAL REGISTRATION INFORMATION: The trial is registered with ClinicalTrials.gov (NCT05163288; registered December 6, 2021), EudraCT (2021-005356-10). The first patient was enrolled into the EP on March 8, 2023. The trial was funded by IntraBio Inc. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that NALL reduces disease progression in NPC.
- MeSH
- dítě MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- leucin * analogy a deriváty terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- následné studie MeSH
- neuroprotektivní látky * terapeutické užití MeSH
- Niemannova-Pickova nemoc typu C * farmakoterapie MeSH
- předškolní dítě MeSH
- progrese nemoci MeSH
- stupeň závažnosti nemoci MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
Traditionally, lithic artefacts have served as the principal proxy for the definition of archaeological cultures in the Upper Paleolithic. However, the culture-historical framework in use, constructed unsystematically and shaped by regional research traditions, features a number of widely acknowledged drawbacks. Here we use personal ornaments to explore the nature of Early Upper Paleolithic cultural entities and establish to what extent they represent distinct or evolving cultural adaptations. We present an analysis of an updated georeferenced dataset composed of personal ornaments coming from two key successive Upper Paleolithic technocomplexes, the Aurignacian (42-34,000 years ago) and the Gravettian (34-24,000 years ago). Using a range of multivariate statistics, we demonstrate that, at both European and regional scales, people belonging to these technocomplexes wore similar personal ornaments, though fully-shaped personal ornaments appear more different between technocomplexes. We additionally show that the variability of the Aurignacian ornaments suggests more fragmented cultural clusters compared to the Gravettian, implying more extensive symbolic networks in the latter. Despite a long-standing consensus based on other archaeological proxies, which emphasises the dissimilarity between these cultural entities, our results demonstrate the complex nature of Upper Paleolithic cultures which are characterised by discontinuities in economic and technical systems and continuity in the culturalisation of the body.
- MeSH
- archeologie * MeSH
- dějiny starověku MeSH
- kultura * MeSH
- kulturní evoluce * MeSH
- lidé MeSH
- multivariační analýza MeSH
- Check Tag
- dějiny starověku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
V letošním roce vzpomeneme 105. výročí narození doc. RNDr. Miroslava Polstera, CSc. (1920–1992), přední osobnosti v oboru mikrobiologie, mykotoxikologie a mykologie. Doc. Polster byl mimořádně schopným a vzdělaným odborníkem zaměřeným především na studium plísní a jejich toxických produktů – mykotoxinů (např. aflatoxinů, kyseliny cyklopiazonové, zearalenonu). Své výzkumné výsledky a poznatky bohatě publikoval. Vešel ve známost jako přední československý odborník v uvedené oblasti. Svou bohatou profesní činnost spojil s katedrou hygieny a epidemiologie na Lékařské fakultě Univerzity Jana Evangelisty Purkyně v Brně (dnes Masarykova univerzita), kde působil jako vedoucí vědecký pracovník a pedagog. Po odchodu do důchodu se od roku 1986 zapojil do práce v nově založeném Centru hygieny potravinových řetězců v Brně pod Institutem hygieny a epidemiologie v Praze (dnes Centrum zdraví, výživy a potravin v Brně spadající pod Státní zdravotní ústav v Praze). Pokračoval v odborné a výzkumné činnosti v oblasti mykologie potravin a mykotoxikologie se zaměřením na mykotoxin kyselinu cyklopiazonovou a studium účinků protiplísňových preparátů
This year we will commemorate the 105th birth anniversary of Assoc. Prof. RNDr. Miroslav Polster, CSc. (1920-1992), a leading figure in the field of microbiology, mycotoxicology and mycology. Miroslav Polster was an extremely capable and educated expert focused primarily on the study of microfungi and their toxic products - mycotoxins (e.g. aflatoxins, cyclopiazonic acid, zearalenone). He published his research results and findings extensively and became known as a leading Czechoslovak expert in the aforementioned field. His rich professional activities are affiliated with the Department of Hygiene and Epidemiology of the Faculty of Medicine at UJEP in Brno (now Masaryk University), where he worked as a senior researcher and teacher. After retirement, from 1986 he was involved in professional and research activities in the field of mycology at the newly founded Centre for the Hygiene of Food Chains in Brno, Institute of Hygiene and Epidemiology in Prague (today Centre for Health, Nutrition and Food in Brno, National Institute of Public Health in Prague). He continued his professional and research activities in the field of food and mycotoxicology focusing on cyclopiazonic acid (mycotoxin) and the study of the effects of antifungal preparations.
BACKGROUND: Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study. METHODS: Vivacity-MG3 was a phase 3, randomised, double-blind, placebo-controlled, phase 3 study conducted at 81 outpatient centres with expertise in myasthenia gravis in 17 countries in Asia-Pacific, Europe, and North America. Adults (aged ≥18 years) with generalised myasthenia gravis inadequately controlled with standard-of-care therapy (MG-ADL score ≥6) were randomly assigned (1:1) to either nipocalimab (30 mg/kg loading dose then 15 mg/kg every 2 weeks for maintenance dosing) or placebo infusions every 2 weeks, added to standard-of-care therapy in both groups, for 24 weeks. Randomisation was stratified by antibody status, day 1 MG-ADL total score, and region. The sponsor, investigators, clinical raters, and participants were masked to treatment assignment. The primary endpoint was the difference between nipocalimab and placebo based on least-squares mean change from baseline in MG-ADL total score averaged over weeks 22, 23, and 24 in the intention-to-treat population of patients who were antibody-positive (for AChR, anti-muscle-specific tyrosine kinase [MuSK], or anti-low-density lipoprotein receptor-related protein 4 [LRP4]). Adverse events were assessed in patients who received at least one dose of study drug. This study is registered at ClinicalTrials.gov, NCT04951622; the double-blind phase is completed and an open-label extension phase is ongoing. FINDINGS: Between July 15, 2021, and Nov 17, 2023, 199 patients were enrolled, and 196 patients received study drug (98 in the nipocalimab group and 98 in the placebo group); of these, 153 (77 in the nipocalimab group and 76 in the placebo group) were antibody-positive. The least-squares mean change in MG-ADL score from baseline to weeks 22, 23, and 24 was -4·70 (SE 0·329) in the nipocalimab group versus -3·25 (0·335) in the placebo group (difference -1·45 [95% CI -2·38 to -0·52]; p=0·0024). The incidence of adverse events was similar between groups (82 [84%] of 98 in both the nipocalimab and placebo groups), including infections (42 [43%] of 98 in the nipocalimab group and placebo group) and headache (14 [14%] of 98 in the nipocalimab group and 17 [17%] of 98 in the placebo group). Serious adverse events were reported for nine (9%) of 98 patients in the nipocalimab group and 14 (14%) of 98 patients in the placebo group, three of which had a fatal outcome (nipocalimab: myasthenic crisis; placebo: cardiac arrest and myocardial infarction). INTERPRETATION: Results from the completed double-blind phase of Vivacity-MG3 support the role of nipocalimab, added to standard-of-care therapies, as a safe treatment for sustained disease control over 6 months for a broad population of patients with generalised myasthenia gravis who are antibody-positive. The ongoing open-label extension phase should provide longer term sustained safety and efficacy data with nipocalimab. FUNDING: Janssen Research & Development, LLC, a Johnson & Johnson company.
- MeSH
- činnosti denního života MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- humanizované monoklonální protilátky * terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- myasthenia gravis * farmakoterapie MeSH
- receptory cholinergní imunologie MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Cognitive impairment in Parkinson's disease (PD) is a key non-motor complication during the disease course. OBJECTIVES: A review of detailed cognitive instruments to detect mild cognitive impairment (PD-MCI) or dementia (PDD) is needed to establish optimal tests that facilitate diagnostic accuracy. METHODS: We performed a systematic literature review of tests that assess memory, language including premorbid intelligence, and visuospatial domains (for tests of attention and executive functions see accompanying review) to determine suitability to assess cognition in PD. Based on in-depth scrutiny of psychometric and other relevant clinimetric properties, tests were rated as "recommended," "recommended with caveats," "suggested," or "listed" by the International Parkinson and Movement Disorder Society (IPMDS) panel of experts according to the IPMDS Clinical Outcome Assessment Scientific Evaluation Committee guidelines. RESULTS: We included 39 tests encompassing 48 outcome measures. Seven tests (different versions or subtests of the test counted once) were recommended, including four for memory, one for visuospatial domains, one for language (including three measures), and one for estimated premorbid intelligence. Furthermore, 10 tests (12 measures) were "recommended with caveats," 11 were "suggested," and 11 (15 measures) were "listed." CONCLUSIONS: Recommended neuropsychological tests in memory, visuospatial functions, and language are proposed to guide the assessment of cognitive impairment and its progression in PD-MCI and PDD, and for use in clinical trials to stratify participants or as outcome measures. Novel measures being developed will need extensive validation research to be "recommended." © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
BACKGROUND AND OBJECTIVES: Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS). METHODS: Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received ≥1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies. Patients were randomized to OCR or interferon β-1a for 96 weeks (double-blind controlled treatment period [DBP]), before switching to OCR in the open-label extension (OLE). Efficacy assessments included no evidence of disease activity (NEDA-3), 24-week confirmed disability progression (CDP), MRI lesion activity, change in whole-brain volume; with safety outcomes assessed over a 9-year treatment period. RESULTS: Overall, 757 patients were included (interferon-treated n = 382, mean age 36.3 years, 65.7% female; OCR-treated n = 375, mean age 35.5 years, 64.0% female); 505 of 757 (66.7%) completed 9 years of follow-up. The difference in NEDA status between OCR-treated and interferon-treated patients achieved during the DBP (72.5% and 43.8%, respectively, odds ratio 3.48, 95% CI 2.52-4.81) was maintained throughout the 7-year OLE (48.2% vs 25.7%; odds ratio 2.72, 95% CI 1.94-3.82). No 24-week CDP was observed in 78.7% of OCR-treated patients over 9 years. Brain volume loss over the entire study period remained numerically higher among patients starting OCR later (p = 0.09 at OLE at week 336). During the DBP, safety profiles in both groups were similar; no new safety signals were observed during the OLE. Over >9 years of continuous OCR treatment, the rate of infections remained low and stable over time. DISCUSSION: A higher proportion of OCR-treated patients achieved NEDA status compared with interferon-treated patients during the DBP, which was maintained throughout the OLE. After switching to OCR, disability accrual and brain volume loss among interferon-treated patients became similar to the OCR-OCR group, but disability and brain volume loss accrued during interferon treatment were not recovered. Possible study limitations include assessment bias due to unmaintained blinding during the OLE. These data support OCR as first-line therapy for these patients. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that OCR delays disease progression in treatment-naïve patients with early-stage RMS.
- MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- humanizované monoklonální protilátky * škodlivé účinky terapeutické užití aplikace a dávkování MeSH
- imunologické faktory * škodlivé účinky aplikace a dávkování terapeutické užití MeSH
- interferon beta 1a terapeutické užití aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- progrese nemoci MeSH
- relabující-remitující roztroušená skleróza * farmakoterapie diagnostické zobrazování MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 109/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017-004012-19). Oral rilzabrutinib 400 mg bid was given over 24 weeks, with optional long-term extension (LTE). Primary endpoints were safety and platelet counts ≥ 50 × 109/L on ≥ 8 of the last 12 weeks of main treatment without rescue medication. From 22 March2018 to 31 January2023, 26 patients were enrolled. Patients had baseline median platelet count 13 × 109/L, ITP duration 10.3 years, and six prior ITP therapies (46% splenectomized). Nine (35%) patients achieved the primary endpoint. Platelet counts ≥ 50 × 109/L or ≥ 30 × 109/L and doubling from baseline without rescue therapy were sustained for a mean 9.3 weeks. 11 (42%) LTE-eligible patients were ongoing with median LTE platelet > 80 × 109/L. Three (12%) patients received rescue medication during main treatment, none in LTE. Clinically meaningful improvements were observed in fatigue and women's health. With a median treatment duration of 167 days (main treatment), 16 (62%) patients had ≥ 1 treatment-related adverse event (AE), mainly grade 1, including diarrhea (35%), headache (23%), and nausea (15%). There was no treatment-related grade ≥ 2 bleeding/thrombotic events/infections, serious AE, or death. Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients. Trial Registration: NCT03395210, EudraCT 2017-004012-19.
- MeSH
- aplikace orální MeSH
- dospělí MeSH
- idiopatická trombocytopenická purpura * farmakoterapie MeSH
- inhibitory proteinkinas * škodlivé účinky terapeutické užití aplikace a dávkování MeSH
- inhibitory tyrosinkinasy MeSH
- lidé středního věku MeSH
- lidé MeSH
- počet trombocytů MeSH
- proteinkinasa BTK * antagonisté a inhibitory MeSH
- pyrazoly terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- pyrimidiny aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze I MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
INTRODUCTION: ND0612 is being investigated as a continuous, subcutaneous levodopa/carbidopa infusion, in combination with oral levodopa/carbidopa, for motor fluctuations in Parkinson's disease (PD). One-year data from the ongoing BeyoND study (NCT02726386) showed that the ND0612 regimen was safe and well tolerated and provided a sustained ≥2-h improvement in daily Good ON-time through 12 months of treatment. METHODS: We describe 3-year safety and efficacy outcomes for participants who completed 12 months of ND0612 treatment in the core study period and entered the extension phase. RESULTS: Of the 214 enrolled participants, 120 completed the core 1-year period, and 114 participants continued into the extension phase. Of these, 95/114 (83.3 %) completed 2 years and 77/114 (67.5 %) completed 3 years of study treatment. Key reasons for discontinuation were treatment-emergent adverse events (TEAEs) (n = 5 and n = 11 after 2 and 3 years, respectively) and withdrawal of consent (n = 9 and n = 5, respectively). TEAEs were reported by 105/114 (92.1 %) participants in Year 1, 77/114 (67.5 %) in Year 2, and 73/95 (76.8 %) in Year 3. While most participants experienced infusion site reactions, these led to discontinuation in only five participants during this extension. At Month 36, the mean reduction in OFF-time from baseline was 2.81 h and the increase in Good ON-time was 2.79 h. CONCLUSIONS: Three-year results from this open-label study support the long-term safety, tolerability, and efficacy of ND0612. For participants who entered the extension phase, the high rate of retention supports a favorable benefit-risk ratio of the ND0612 regimen for patients with PD experiencing motor fluctuations.
- MeSH
- antiparkinsonika * aplikace a dávkování škodlivé účinky MeSH
- fixní kombinace léků * MeSH
- karbidopa * aplikace a dávkování MeSH
- levodopa * aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc * farmakoterapie MeSH
- senioři MeSH
- subkutánní infuze * MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Building reliable and robust quantitative structure-property relationship (QSPR) models is a challenging task. First, the experimental data needs to be obtained, analyzed and curated. Second, the number of available methods is continuously growing and evaluating different algorithms and methodologies can be arduous. Finally, the last hurdle that researchers face is to ensure the reproducibility of their models and facilitate their transferability into practice. In this work, we introduce QSPRpred, a toolkit for analysis of bioactivity data sets and QSPR modelling, which attempts to address the aforementioned challenges. QSPRpred's modular Python API enables users to intuitively describe different parts of a modelling workflow using a plethora of pre-implemented components, but also integrates customized implementations in a "plug-and-play" manner. QSPRpred data sets and models are directly serializable, which means they can be readily reproduced and put into operation after training as the models are saved with all required data pre-processing steps to make predictions on new compounds directly from SMILES strings. The general-purpose character of QSPRpred is also demonstrated by inclusion of support for multi-task and proteochemometric modelling. The package is extensively documented and comes with a large collection of tutorials to help new users. In this paper, we describe all of QSPRpred's functionalities and also conduct a small benchmarking case study to illustrate how different components can be leveraged to compare a diverse set of models. QSPRpred is fully open-source and available at https://github.com/CDDLeiden/QSPRpred .Scientific ContributionQSPRpred aims to provide a complex, but comprehensive Python API to conduct all tasks encountered in QSPR modelling from data preparation and analysis to model creation and model deployment. In contrast to similar packages, QSPRpred offers a wider and more exhaustive range of capabilities and integrations with many popular packages that also go beyond QSPR modelling. A significant contribution of QSPRpred is also in its automated and highly standardized serialization scheme, which significantly improves reproducibility and transferability of models.
- Publikační typ
- časopisecké články MeSH