• MeSH
• Electroencephalography MeSH
• Cognition physiology   MeSH
• Cognitive Science methods   MeSH
• Humans MeSH
• Brain physiology   MeSH
• Neurons physiology   MeSH
• Perception physiology   MeSH
• Reflex physiology   MeSH
• Sleep Stages MeSH
• Consciousness * physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• MeSH
• Central Nervous System anatomy & histology   physiology   MeSH
• Dissection MeSH
• Electroencephalography MeSH
• Humans MeSH
• Brain * anatomy & histology   surgery   physiology   pathology   MeSH
• Neuroimaging methods   MeSH
• Consciousness Disorders MeSH
• Models, Theoretical MeSH
• Consciousness physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• Publication type
• Published Erratum MeSH

BACKGROUND: The research on possible cerebral involvement in Crohn's disease (CD) has been largely marginalized and failed to capitalize on recent developments in magnetic resonance imaging (MRI). OBJECTIVE: This cross-sectional pilot study searches for eventual macrostructural and microstructural brain affection in CD in remission and early after the disease onset. METHODS: 14 paediatric CD patients and 14 healthy controls underwent structural, diffusion weighted imaging and quantitative relaxation metrics acquisition, both conventional free precession and adiabatic rotating frame transverse and longitudinal relaxation time constants as markers of myelination, iron content and cellular loss. RESULTS: While no inter-group differences in cortical thickness and relaxation metrics were found, lower mean diffusivity and higher intracellular volume fraction were detected in CD patients over vast cortical regions essential for the regulation of the autonomous nervous system, sensorimotor processing, cognition and behavior, pointing to wide-spread cytotoxic oedema in the absence of demyelination, iron deposition or atrophy. CONCLUSION: Although still requiring further validation in longitudinal projects enrolling larger numbers of subjects, this study provides an indication of wide-spread cortical oedema in CD patients very early after the disease onset and sets possible directions for further research.

• Publication type
• Journal Article MeSH

BACKGROUND: Placenta previa is the abnormal implantation of the placenta into the lower segment of the uterus, is associated with adverse maternal and fetal outcomes such as placenta accreta spectrum disorders, antepartum and postpartum hemorrhage, fetal growth restriction, prematurity, stillbirth and neonatal death, thrombophlebitis, and septicemia. The aim of the study was to assess retrospectively how the later onset of placenta previa affects the microRNA expression profile in the whole peripheral blood during the first trimester of gestation. METHODS: Regarding the occurrence of the association between aberrant microRNA expression profiles at early stages of gestation and later onset of various pregnancy-related complications, we selected for the study pregnancies developing placenta previa as the only pregnancy-related disorder. In total, 24 singleton pregnancies diagnosed with placenta previa that underwent first-trimester prenatal screening and delivered on-site within the period November 2012-May 2018 were included in the study. Overall, 80 normal pregnancies that delivered appropriate-for-gestational age newborns after completing 37 weeks of gestation were selected as the control group based on the equality of the length of biological sample storage. RESULTS: Downregulation of multiple microRNAs (miR-20b-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-103a-3p, miR-130b-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-195-5p, miR-210-3p, miR-342-3p, and miR-574-3p) was observed in pregnancies destined to develop placenta previa. The combination of seven microRNAs (miR-130b-3p, miR-145-5p, miR-155-5p, miR-181a-5p, miR-210-3p, miR-342-3p, and miR-574-3p) showed the highest accuracy (AUC 0.937, p < 0.001, 100.0% sensitivity, 83.75% specificity) to differentiate, at early stages of gestation, between pregnancies with a normal course of gestation and those with placenta previa diagnosed in the second half of pregnancy. Overall, 75% of pregnancies destined to develop placenta previa were correctly identified at 10.0% FPR. CONCLUSION: Consecutive large-scale analyses must be performed to verify the reliability of the proposed novel early predictive model for placenta previa occurring as the only pregnancy-related disorder.

• Publication type
• Journal Article MeSH

BACKGROUND AND OBJECTIVES: Early treatment of multiple sclerosis (MS) reduces disease activity and the risk of long-term disease progression. Effectiveness of ocrelizumab is established in relapsing MS (RMS); however, data in early RMS are lacking. We evaluated the 4-year effectiveness and safety of ocrelizumab as a first-line therapy in treatment-naive patients with recently diagnosed relapsing-remitting MS (RRMS). METHODS: ENSEMBLE was a prospective, 4-year, international, multicenter, single-arm, open-label, phase IIIb study. Patients were treatment naive, aged 18-55 years, had early-stage RRMS with a disease duration ≤3 years, Expanded Disability Status Scale (EDSS) score ≤3.5, and ≥1 clinically reported relapse(s) or ≥1 signs of brain inflammatory activity on MRI in the prior 12 months. Patients received IV ocrelizumab 600 mg every 24 weeks. Effectiveness endpoints over 192 weeks were proportion of patients with no evidence of disease activity (NEDA-3; defined as absence of relapses, 24-week confirmed disability progression [CDP], and MRI measures, with prespecified MRI rebaselining at week 8), 24-week/48-week CDP and 24-week confirmed disability improvement, annualized relapse rate (ARR), mean change in EDSS score from baseline, and safety. Cognitive status, patient-reported outcomes, and serum neurofilament light chain (NfL) were assessed. Descriptive analysis was performed on the intention-to-treat population. RESULTS: Baseline characteristics (N = 678) were consistent with early-stage RRMS (n = 539 patients, 64.6% female, age 40 years and younger; median age: 31.0 years; duration since: MS symptom onset 0.78 years, RRMS diagnosis 0.24 years; mean baseline EDSS score [SD] 1.71 [0.95]). At week 192, most of the patients had NEDA-3 (n = 394/593, 66.4%), 85.0% had no MRI activity, 90.9% had no relapses, and 81.8% had no 24-week CDP over the study duration. Adjusted ARR at week 192 was low (0.020, 95% CI 0.015-0.027). NfL levels were reduced to and remained within the healthy donor range, by week 48 and week 192, respectively. No new or unexpected safety signals were observed. DISCUSSION: Disease activity based on clinical and MRI measures was absent in most of the patients treated with ocrelizumab over 4 years in the ENSEMBLE study. Safety was consistent with the known profile of ocrelizumab. Although this single-arm study was limited by lack of a parallel group for comparison of outcome measures, the positive benefit-risk profile observed may provide confidence to adopt ocrelizumab as a first-line treatment in newly diagnosed patients with early RMS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that adult patients with early-stage MS who were treatment naive maintained low disease activity (NEDA-3) over 4 years with ocrelizumab treatment; no new safety signals were detected. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier NCT03085810; first submitted March 16, 2017; first patient enrolled: March 27, 2017; available at clinicaltrials.gov/ct2/show/NCT03085810.

• MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   adverse effects   administration & dosage   MeSH
• Immunologic Factors * therapeutic use   adverse effects   administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Adolescent MeSH
• Young Adult MeSH
• Disability Evaluation MeSH
• Disease Progression MeSH
• Prospective Studies MeSH
• Multiple Sclerosis, Relapsing-Remitting * drug therapy   diagnostic imaging   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH

The antibiotic resistance genes (ARGs) limit the susceptibility of bacteria to antimicrobials, representing a problem of high importance. Current research on the presence of ARGs in microorganisms focuses mainly on humans, livestock, hospitals, or wastewater. However, the spectrum of ARGs in the dust resistome in workplaces and households has gone relatively unexplored. This pilot study aimed to analyze resistome in indoor dust samples from participants' workplaces (a pediatric hospital, a maternity hospital, and a research center) and households and compare two different approaches to the ARGs analysis; high-throughput quantitative PCR (HT-qPCR) and whole metagenome shotgun sequencing (WMGS). In total, 143 ARGs were detected using HT-qPCR, with ARGs associated with the macrolides, lincosamides, and streptogramin B (MLSB) phenotype being the most abundant, followed by MDR (multi-drug resistance) genes, and genes conferring resistance to aminoglycosides. A higher overall relative quantity of ARGs was observed in indoor dust samples from workplaces than from households, with the pediatric hospital being associated with the highest relative quantity of ARGs. WMGS analysis revealed 36 ARGs, of which five were detected by both HT-qPCR and WMGS techniques. Accordingly, the efficacy of the WMGS approach to detect ARGs was lower than that of HT-qPCR. In summary, our pilot data revealed that indoor dust in buildings where people spend most of their time (workplaces, households) can be a significant source of antimicrobial-resistant microorganisms, which may potentially pose a health risk to both humans and animals.

• MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Bacteria genetics   isolation & purification   drug effects   classification   MeSH
• Genes, Bacterial genetics   MeSH
• Drug Resistance, Bacterial genetics   MeSH
• Family Characteristics MeSH
• Real-Time Polymerase Chain Reaction MeSH
• Humans MeSH
• Metagenome MeSH
• Air Microbiology MeSH
• Pilot Projects MeSH
• Dust * analysis   MeSH
• Workplace * MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Air Pollution, Indoor MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

OBJECTIVES: Propose a methodology to identify COVID-19 associated deaths using healthcare billing records and evaluate its effectiveness by comparing the results with excess mortality data from 2020 to 2022 and confirmed COVID-19 deaths. METHODS: A retrospective quantitative analysis was conducted by merging healthcare billing records with cause of death data. The term "COVID-19 associated death" was defined as any death occurring within a defined timeframe following a confirmed contact with COVID-19. This category includes individuals who died directly due to COVID-19, with COVID-19 as a contributing factor, or as an aftermath of a COVID-19 infection, as well as those who died from other causes but had previously contracted COVID-19. This broader definition provides a more comprehensive measure of excess mortality compared to the officially confirmed COVID-19 deaths attributed to the virus. RESULTS: We identified 35,399 COVID-19 associated deaths during the 3-year pandemic in Slovakia compared to 21,395 confirmed COVID-19 deaths. CONCLUSION: The identification of COVID-19 associated deaths with our methodology offers a more accurate explanation for the notably high excess mortality observed in Slovakia (31,789 deaths) during the pandemic, relative to the EU27. Given the high level of excess mortality, the officially confirmed deaths are likely underestimated, and the presented methodology provides a more precise measure of mortality. Additionally, healthcare billing records prove valuable in identifying these deaths at the individual patient level using claims data of health insurance companies, which is crucial for implementing targeted preventive measures and improving preparedness for future pandemics.

• MeSH
• COVID-19 * mortality   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Pandemics MeSH
• Cause of Death * MeSH
• Retrospective Studies MeSH
• SARS-CoV-2 MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Slovakia MeSH

OBJECTIVES: The aim of this qualitative study was to identify the main factors that help and hinder adolescents' wellbeing at school using their perspectives and experiences. METHODS: We used data from 45 adolescents in the first year of high school in Slovakia (mean age = 14.98; 22.2% boys). We obtained the data using 11 semi-structured group interviews conducted in 2020/2021. Participants were selected from three types of high school with regard to graduation system. Data was analysed using consensual qualitative research and thematic analysis. RESULTS: We identified three main themes of factors contributing to their wellbeing at school: 1. School (atmosphere and organisation of life at school, physical environment, threats and the ability of school to deal with issues); 2. Relationships (with peers and teachers, and teachers' behaviour towards them); 3. Myself (own perceived obstacles and resilience resources). CONCLUSION: The organisation of life at school, surroundings, threats and dealing with issues importantly affect adolescents' wellbeing. Therefore, adjustment of physical environment and interpersonal competences of teachers, supporting of resilience resources of adolescents should be targets for interventions and prevention programmes at schools.

• MeSH
• Interpersonal Relations MeSH
• Qualitative Research * MeSH
• Humans MeSH
• Adolescent MeSH
• Personal Satisfaction MeSH
• Interviews as Topic MeSH
• Schools * MeSH
• Students psychology   MeSH
• School Teachers psychology   MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Slovakia MeSH

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigms for hematological malignancies. However, more than half of these patients cannot achieve sustainable tumor control, partially due to the inadequate potency of CAR-T cells in eradicating tumor cells. T cells are crucial components of the anti-tumor immune response, and multiple intrinsic T-cell features significantly influence the outcomes of CAR-T cell therapy. Herein, we review progressing research on T-cell characteristics that impact the effectiveness of CAR-T cells, including T-cell exhaustion, memory subsets, senescence, regulatory T-cells, the CD4+ to CD8+ T-cell ratio, metabolism, and the T-cell receptor repertoire. With comprehensive insight into the biological processes underlying successful CAR-T cell therapy, we will further refine the applications of these novel therapeutic modalities, and enhance their efficacy and safety for patients.

• MeSH
• Receptors, Chimeric Antigen * immunology   MeSH
• Hematologic Neoplasms * therapy   immunology   MeSH
• Immunotherapy, Adoptive * methods   MeSH
• Humans MeSH
• T-Lymphocytes immunology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH