While measles-mumps and rubella vaccines (MMR) have reduced mumps incidence, outbreaks continue to occur in developed countries. The aim of the study was to evaluate the serological status against mumps and its association with vaccination history among medical students in Catalonia (Spain). A cross-sectional study was conducted during 2023-2025 among medical students attending four university teaching-units. Participants completed a questionnaire and provided blood samples for mumps IgG testing. Associations between positive serology and vaccination status and the independent variables were assessed calculating adjusted OR (aOR) and 95% confidence interval (CI) after adjustment for age, sex, and degree year. Among 235 participants, 94.5% had received 2-MMR doses, and 94.9% had been vaccinated more than 15 years earlier. Complete vaccination was associated with being a 5th-year student (aOR 5.45; 95%CI: 1.38-21.50); 80.4% showed positive IgG, being higher in women (aOR 2.52; 95%CI: 1.20-5.30). Seropositivity declined with increasing time since last vaccination. Although the proportion of students serologically protected is acceptable, more than 15 years have passed since the last vaccine dose in most of the students and waning immunity is expected. The recommendation of a third MMR dose for medical students and healthcare workers in mumps outbreak settings should be considered.

Infants and children under 5 years of age face a high risk of severe complications, including pneumonia and neurologic issues, from influenza virus infection. Hospital surveillance data can provide guidance for immunization recommendation policies to prevent severe influenza complications in the pediatric population. The aim of this study was to investigate the factors associated with influenza virus type and subtype in children and adolescents hospitalized with laboratory-confirmed influenza and compare the results obtained in previous analyses from 2010/11 to 2015/16 (P1) and 2016/17 to 2019/20 (P2). We carried out a retrospective descriptive study during ten influenza seasons (2010-2011 to 2019-2020) on laboratory-confirmed influenza in cases aged 0-17 years hospitalized for severe acute influenza virus infection (SHLCI). A total of 528 pediatric hospitalizations with laboratory-confirmed influenza were reported, 274 (51.9%) were male and 285 (54.0%) were aged 1-4 years. One hundred and two patients (19.3%) required ICU admission; 112 (21.2%) had preexisting comorbidities. The median length of stay was 5 days (range: 1-129). The main complications were pneumonia (61.8%), ARDS (29.7%) and 4 deaths. There was no significant difference in the incidence of complications according to virus type. The distribution according to influenza virus type and subtype was as follows: 79.4% had influenza A (43.7% H1N1pdm09, 14.1% H3N2), and 20.6% had influenza B. Only 5.4% had received the seasonal influenza vaccine. Our results confirm that, among the pediatric population, severe influenza predominantly affects younger children, who are often previously healthy, and is associated with substantial complications and ICU burden. The low degree of vaccination coverage among hospitalized children emphasizes the need to improve influenza immunization strategies in pediatric populations.

Measles is a highly contagious infectious disease. The importance of vaccinating healthcare workers (HCW) and medical students as future HCW is underlined by the numerous measles outbreaks in health institutions. We aimed to assess the factors associated with complete vaccination, and measles serological status in relation to vaccination history among medical students in Catalonia (Spain). A cross-sectional study was conducted among medical students attending four university teaching-units during the 2023–2024 and 2024–2025 academic years. Medical students completed a questionnaire and provided blood samples for measles IgG testing. Associations between positive serology, vaccination status, and independent variables (age, sex, country of birth, degree year, future speciality, vaccination attitudes, and measles vaccination history) were assessed using the odds ratio (OR) and 95

INTRODUCTION:Chronic hepatitis B (CHB) virus infection leads to severe complications, cirrhosis and hepatocellular carcinoma (HCC). The main objective of this study was to develop an ARIMA-based model to forecast the progression of global hospital discharges, due to cirrhosis and HCC related to chronic hepatitis B. METHODS:Retrospective observational study of monthly incidence of CHB related hospitalization discharges from 2005 to 2021 in Spain. Data were obtained through the Spanish Minimum dataset of hospital discharge registry (CMBDH) of the Health Ministry. Main diagnosis of CHB, liver cirrhosis and HCC encoded by International Medical codes (ICM-9 and ICM-10) were used. Descriptive and time series analysis was performed with forecasts made for 2022 using seasonal ARIMA and ARIMAX models. Data stationarity was achieved via a square root Box-Cox transformations and differencing. Model selection used was AIC, BIC, MAPE, and forecasting precision. Analysis was performed in R (version 4.5.0). RESULTS:The total number of discharges related to hepatitis B was 6743, 58% were due to HCC and 42% to cirrhosis diagnosis. Median age was 59 years (range: 7 to > 100), being 83.4% men. The global chronic hepatitis B (CHB) related workload values range from 10 to 55 monthly discharges, while hepatitis B related to HCC and cirrhosis range from 4 to 34 and 1-29 discharges, respectively. The best fit and 2022 forecasts found for CHB and HCC time series was obtained with the approximate Gaussian [Formula: see text]-ARIMAX (6,0,0) (0,1,1) _12 model. This model after treating outliers, removes seasonal patterns and captures the series' autoregressive dynamics with an AR(6) and seasonal MA(1) noise with expression: [Formula: see text] with ε ~ N(0, σ²) and in the square root scale. CONCLUSION:Both ARIMA and ARIMAX models play critical roles in forecasting CHB-related HCC and cirrhosis, enabling better disease monitoring, healthcare resources, and intervention assessment. ARIMAX provided more accurate context-aware predictions, making it especially valuable for public health decision-making.

Abstract Despite important advances in understanding the etiopathology of multiple sclerosis, factors determining disease progression remain partially understood and often difficult to predict. Specific diagnostic and prognostic biomarkers are needed to optimize the risk-benefit ratio of treatment for each patient. The aim of our study was to identify a cerebrospinal fluid proteomic signature associated with diagnosis and short- to mid-term prognosis across the multiple sclerosis continuum. Our multicentric cohort study analyzed CSF samples from 120 patients using a proteomics data-independent acquisition strategy. Differentially expressed proteins were identified across diagnostic groups: 62 patients with multiple sclerosis, 15 patients with clinically isolated syndrome, and 43 healthy controls. We also compared the CSF of patients with no evidence of disease activity with those with disease activity at 2 and 5 years of follow-up. A diagnostic and prognostic classification model was built using iterative cross-validated logistic regression models on shared differentially expressed proteins across these two comparisons. A total of 1,257 proteins were quantified, and 162 differentially expressed proteins were identified across comparisons. We identified a set of ten proteins associated with the diagnosis and prognosis of multiple sclerosis, including previously identified potential biomarkers (CH3L2, IGHG1, IGKC, LAMP2, ADA2), proteins known to be involved in the pathophysiology of multiple sclerosis (A0A8J8YUT9, AT2A2, CO3A1) and two yet unreported proteins (DSC2 and MMRN2). Multivariate models based on these proteins achieved good accuracy for the diagnosis of MS compared with CIS (area under the receiver operating characteristics curve [AUROC] up to 80% using 3 proteins) and prognosis (NEDA vs. EDA; AUROC up to 96% at 2 and 5 years; using 5 proteins). These results, which will require further investigation to validate the new biomarkers, open new perspectives on multiple sclerosis pathophysiology and therapeutic targets.

Mass spectrometry-based proteomics is an essential technique in contemporary biomedicine, offering quantitative, sensitive, and rapid analysis of proteomes. Recent advancements in mass spectrometry have enabled the acquisition of data from increasingly large-scale experiments, often conducted in core facilities and research infrastructures. While automated tools exist to assess instrument performance using predefined control samples, the analysis of experimental samples typically occurs postacquisition, which can delay decision-making and lead to potential data integrity issues. To address these challenges, we developed QSample, an open-source automated system for rapidly monitoring quality indicators in proteomics samples during data collection. QSample enhances the quality control framework by facilitating prompt actions and fast decision-making, ensuring that proteomics core facilities deliver data that adhere to best research practices.

BACKGROUND:Huntington's disease (HD) is the most frequent autosomal dominant neurodegenerative disorder, which is caused by a CAG repeat expansion in the HTT gene. Despite its well-defined genetic origin, there is currently no cure, and reliable biomarkers for disease progression and pathophysiology remain limited. Mutant huntingtin protein accumulates in endosomal compartments, disrupting endosomal trafficking and potentially affecting the biogenesis, release, and cargo of exosomes-extracellular vesicles (EVs) derived from the endosomal pathway. However, the role of exosomes in HD pathogenesis and their potential as biomarkers has been underexplored. In this work, we investigated whether the levels and content of small EV subpopulations, including exosomes, are altered in the brains of HD patients. METHODS:We analyzed two distinct subpopulations of small EVs from the striatum and cortex of postmortem HD brains at early and advanced neuropathological stages, as well as from age-matched controls. EVs were isolated by differential ultracentrifugation and high-resolution iodixanol density gradient centrifugation, and analyzed by Western blotting, electron microscopy, NTA, and proteomics using mass spectrometry. EV secretion was also analyzed in primary fibroblasts derived from HD patients and healthy controls. RESULTS:Mass spectrometry data revealed HD-associated alterations in EV protein content, particularly proteins related to the endosomal system. Our data also indicate that the level of ectosomes increased in the HD cortex, whereas exosomes were reduced in the HD striatum compared to controls. In terms of EV content, EVs from HD brains showed increased levels of Annexin A2 and decreased levels of Alix, a key component of the endosomal sorting complex required for transport (ESCRT). Alix depletion in EVs mirrored a progressive reduction of Alix in brain tissue, correlating with disease severity based on Vonsattel staging. In vitro, HD fibroblasts secreted EVs with reduced Alix content, despite no significant difference in cellular Alix levels compared to controls. CONCLUSIONS:These findings highlight disease-specific changes in EV populations and cargo in HD, and identify Alix as a potential neuropathological marker. This study advances our understanding of the role of brain-derived EVs in HD and underscores their potential utility in biomarker discovery.

Telomere length is an important indicator of biological age and a complex multi-factor trait. To date, the telomere interactome for comprehending the high-dimensional biological aspects linked to telomere regulation during childhood remains unexplored. Here we describe the multi-omics signatures associated with childhood telomere length. This study included 1001 children aged 6 to 11 years from the Human Early-life Exposome (HELIX) project. Telomere length was quantified via qPCR in peripheral blood of the children. Blood DNA methylation, gene expression, miRNA expression, plasma proteins and serum and urinary metabolites were measured through microarrays or (semi-) targeted assays. The association between each individual omics feature and telomere length was assessed in omics-wide association analyses. In addition, a literature-guided, sparse supervised integration method was applied to multiple omics, and latent components were extracted as predictors of child telomere length. The association of these latent components with early-life aging risk factors (child lifestyle, body mass index (BMI), exposure to smoking, etc.), were interrogated. After multiple-testing correction, only two CpGs (cg23686403 and cg16238918 at PARD6G gene) out of all the omics features were significantly associated with child telomere length. The supervised multi-omics integration approach revealed robust associations between latent components and child BMI, with metabolites and proteins emerging as the primary contributing features. In these latent components, the contributing molecular features were known as involved in metabolism and immune regulation-related pathways. Findings of this multi-omics study suggested an intricate interplay between telomere length, metabolism and immune responses, providing valuable insights into the molecular underpinnings of the early-life biological aging.

BACKGROUND:Early-life environmental exposures are suspected to modify important immune processes related to child health. Yet, no study has investigated immunotoxicity in relation to the exposome and multiple health domains simultaneously. METHODS:Among 845 children (median age 8) from six European birth cohorts included in the Human Early-Life Exposome (HELIX) project, we identified immune signatures of a health score covering cardiometabolic, respiratory/allergic and neurodevelopmental health in children. Those signatures were identified from blood samples in three biological layers (white blood cell (WBC) composition, plasma proteins concentrations, DNA methylation of WBCs) using an advanced factorial analysis supervised on the child health score. Second, we estimated the association between the identified signatures and 91 pre- and postnatal environmental exposures. RESULTS:Three key immune signatures were associated with a better health score in children: a first protein signature characterizing a low inflammatory profile (R2 = 17 %), a second protein signature characterizing a low inflammatory profile with balanced antiviral Th response (R2 = 2 %), and a WBC signature characterizing an immuno-regulatory and naïve profile (R2 = 2 %). In childhood, less exposure to indoor air pollutants, proximity to blue spaces and public transport, healthy dietary habits and higher social capital were associated with the three immune signatures related to a better health score (regression p-values < 0.05). One signature was identified from DNA methylation, but was not significantly associated with the health score nor with the exposome. CONCLUSIONS:These findings highlight the influence of early-life environmental exposures on key inflammatory processes associated with the cardiometabolic, respiratory and neurodevelopmental health of children.

BACKGROUND:Obesity is a multi-cause chronic disease recognized across the lifespan, with childhood obesity prevalence rising over the past decades. Although exposome-wide association studies have identified early-life environmental drivers of child obesity, and explored the multi-omics signatures of the exposome of children, it is understudied whether the combined effects of multiple exposures are potentially mediated by multi-omics. METHODS:Within the Human Early Life Exposome (HELIX) project, 1041 mother-child pairs were surveyed for a wide range of environmental exposures including over 354 prenatal and childhood exposures. Multi-omics molecular features were measured during childhood, encompassing the blood methylome and transcriptome, plasma proteins and urinary and serum metabolites. Exposome and multi-omics features were integrated into latent factors by Multi-omics Factor Analysis, based on which structural equation modelling was used to assess whether multi-omics mediated associations between exposome and child body mass index (BMI). RESULTS:Key findings included: (i) prenatal nutrition, exercise, and passive smoking influencing BMI via DNA methylation of HOXA5 and Tenascin XB; (ii) childhood exposure to PCBs and phenols linked with BMI through inflammation and coagulation pathways; and (iii) childhood PCB and dietary exposures associated with BMI via immune pathways. CONCLUSIONS:This novel untargeted workflow elucidated biological mechanisms linking environmental exposures to child obesity, potentially supporting targeted public health interventions.

Childhood obesity poses a significant public health challenge, yet the molecular intricacies underlying its pathobiology remain elusive. Leveraging extensive multi-omics profiling (methylome, miRNome, transcriptome, proteins and metabolites) and a rich phenotypic characterization across two parts of Europe within the population-based Human Early Life Exposome project, we unravel the molecular landscape of childhood obesity and associated metabolic dysfunction. Our integrative analysis uncovers three clusters of children defined by specific multi-omics profiles, one of which characterized not only by higher adiposity but also by a high degree of metabolic complications. This high-risk cluster exhibits a complex interplay across many biological pathways, predominantly underscored by inflammation-related cascades. Further, by incorporating comprehensive information from the environmental risk-scape of the critical pregnancy period, we identify pre-pregnancy body mass index and environmental pollutants like perfluorooctanoate and mercury as important determinants of the high-risk cluster. Overall, our work helps to identify potential risk factors for prevention and intervention strategies early in the life course aimed at mitigating obesity and its long-term health consequences. Obesity encompasses numerous interconnected pathological mechanisms. Here, the authors show that integrating multi-omics data uncovers distinct molecular profiles and prenatal factors linked to childhood obesity and metabolic dysfunction, providing insights for early prevention and intervention strategies.

Motivation:In mass spectrometry-based proteomics, the availability of peptide prior knowledge has improved our ability to assign fragmentation spectra to specific peptide sequences. However, some peptides exhibit similar analytical values and fragmentation patterns, which makes them nearly indistinguishable with current data analysis tools. Results:Here we developed the Mass Spectrometry Content Information (MSCI) Python package to tackle the challenges of peptide identification in mass spectrometry-based proteomics, particularly regarding indistinguishable peptides. MSCI provides a comprehensive toolset that streamlines the workflow from data import to spectral analysis, enabling researchers to effectively evaluate fragmentation similarity scores among peptide sequences and pinpoint indistinguishable peptide pairs in a given proteome. Availability and implementation:MSCI is implemented in Python and it is released under a permissive MIT license. The source code and the installers are available on GitHub at https://github.com/proteomicsunitcrg/MSCI.

BACKGROUND:Hepatitis A is an acute disease of the liver caused by the hepatitis A virus (HAV). Chronic liver disease, other viral hepatitis coinfections, and age over 50 years are the main host factors associated with an increased risk of complications. We investigated the evolution of hepatitis A hospitalizations and in-hospital deaths during 2000-2021 in Spain according to demographic characteristics, presence of other sexually transmitted infections, and vaccination strategy (universal or risk-group vaccination). METHODS:Using data from the Spanish National Health System's Minimum Basic Data Set, we calculated age-standardized cumulative hospitalization incidence and 95% confidence interval (CI), factors associated with hospital stay, and hospitalization deaths. Adjusted OR (aOR) values were calculated using a multivariate logistic regression model. RESULTS:The Spanish cumulative hospitalization incidence for hepatitis A over the 22-year period was 8.84 per 1 000 000 globally and 12.54 and 5.26 per 1 000 000 for men and women, respectively (RR = 2.38; 95% CI: 2.28-2.50). Median length of stay was 4 days (range 0-85). Factors associated with hospitalization >7 days were age groups 40-59 and ≥60 years (aOR 1.58; 95% CI: 1.37-1.82 and aOR 5.09; 95% CI: 4.01-6.47, respectively), cirrhosis (aOR 6.11; 95% CI: 2.59-14.43), and presence of HIV and HBV (aOR 1.65; 95% CI: 1.15-2.38 and 2.01; 95% CI: 1.03-3.63, respectively). In-hospital deaths were associated with age ≥ 60 years (aOR 35.23; 95% CI: 11.12-111.58), hospitalization >7 days (aOR 4.37; 95% CI: 1.80-10.58), cirrhosis (aOR 8.84; 95% CI: 2.37-32.99), and HCV infection (aOR 8.66; 95% CI: 1.57-47.87). The cumulative hospitalization incidence was lower in regions implementing universal vaccination (RR 0.79; 95% CI: 0.75-0.84). CONCLUSION:Results of studies based on characteristics of hospitalized hepatitis A cases taking into account the existing prevention policies can be useful to have a better knowledge about its evolving epidemiology and to improve the prevention and control of the disease.

Chromocenters are established after the 2-cell (2C) stage during mouse embryonic development, but the factors that mediate chromocenter formation remain largely unknown. To identify regulators of 2C heterochromatin establishment in mice, we generated an inducible system to convert embryonic stem cells (ESCs) to 2C-like cells. This conversion is marked by a global reorganization and dispersion of H3K9me3-heterochromatin foci, which are then reversibly formed upon re-entry into pluripotency. By profiling the chromatin-bound proteome (chromatome) through genome capture of ESCs transitioning to 2C-like cells, we uncover chromatin regulators involved in de novo heterochromatin formation. We identified TOPBP1 and investigated its binding partner SMARCAD1. SMARCAD1 and TOPBP1 associate with H3K9me3-heterochromatin in ESCs. Interestingly, the nuclear localization of SMARCAD1 is lost in 2C-like cells. SMARCAD1 or TOPBP1 depletion in mouse embryos leads to developmental arrest, reduction of H3K9me3, and remodeling of heterochromatin foci. Collectively, our findings contribute to comprehending the maintenance of chromocenters during early development.

The DNA damage repair kinase ATM is phosphorylated by the NF-κB pathway kinase IKKα, resulting in enhanced DNA damage repair through the nonhomologous end-joining pathway. Thus, inhibition of IKKα enhances the efficacy of cancer therapy based on inducing DNA damage. Here, we found a role for the IKK regulatory subunit NEMO in DNA damage repair mediated by ATM and IKKα. Exposure to damaging agents induced the interaction of NEMO with a preformed ATM-IKKα complex, which was required to target active ATM and IKKα to chromatin for efficient DNA damage repair but not for activating ATM. Recognition of damaged DNA by the IKKα-NEMO-ATM complex was facilitated by the interaction between NEMO and histones and depended on the ADP ribosylation of histones by the enzyme PARP1. NEMO-deficient cells showed increased activity of the kinase ATR, and inhibition of ATR potentiated the effect of chemotherapy in cells lacking NEMO or IKKα. Bioinformatic analysis of colorectal cancer datasets demonstrated that the expression of genes encoding IKKα, NEMO, and ATM correlated with poor patient prognosis, suggesting that the mechanism linking these three elements may be clinically relevant.

Cerebrospinal fluid (CSF) is a valuable liquid biopsy for identifying protein biomarkers in neurological diseases, yet its proteome profiling faces challenges due to the large dynamic range of protein abundances. In this study, we assessed the effectiveness of a commercial enrichment strategy, initially developed for plasma samples, in enhancing the detection of low-abundance proteins in human CSF. We demonstrate significant improvements in protein identification and coverage depth while maintaining high reproducibility and low coefficients of variation. These findings underscore the potential of this enrichment strategy to facilitate rapid and sensitive CSF analysis, advancing biomarker discovery in neurological research. SIGNIFICANCE: This article highlights the effectiveness of a commercial plasma enrichment strategy in enhancing the detection of low-abundance proteins in human CSF. The article shows improvements in proteome coverage and it underscores the potential of this strategy to facilitate rapid and sensitive CSF analysis.

The redox state of proteins is essential for their function and guarantees cell fitness. Peroxiredoxins protect cells against oxidative stress, maintain redox homeostasis, act as chaperones, and transmit hydrogen peroxide signals to redox regulators. Despite the profound structural and functional knowledge of peroxiredoxins action, information on how the different functions are concerted is still scarce. Using global proteomic analyses, we show here that the yeast peroxiredoxin Tsa1 interacts with many proteins of essential biological processes, including protein turnover and carbohydrate metabolism. Several of these interactions are of a covalent nature, and we show that failure of peroxiredoxinylation of Gnd1 affects its phosphogluconate dehydrogenase activity and impairs recovery upon stress. Thioredoxins directly remove TSA1-formed mixed disulfide intermediates, thus expanding the role of the thioredoxin-peroxiredoxin redox cycle pair to buffer the redox state of proteins.

The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections. Acute HBV cases reported to the Spanish National Epidemiological Surveillance Network between 2005 and 2021 were included. For regions starting adolescent vaccination in 1991–1993 and in 1994–1996, HBV incidence rates were compared by calculating the incidence rate ratio (IRR) and 95% confidence interval (CI). We also analysed the 2017 Spanish national seroprevalence survey data. The overall acute HBV incidence per 100,000 persons was 1.54 in 2005 and 0.64 in 2021 (p < 0.001). The incidence in 2014–2021 was lower for regions that started adolescent vaccination in 1991–1993 rather than in 1994–1996 (IRR 0.76; 95% CI 0.72–0.83; p < 0.001). In the 20–29 age group, incidence in regions that started adolescent vaccination in 1991–1993 was also lower (IRR 0.87; 95% CI 0.77–0.98; p = 0.02 in 2005–2013 and IRR 0.71; 95% CI 0.56–0·90; p < 0.001 in 2014–2021). Anti-HBc prevalence in the 35–39 age group was lower in the regions that started vaccination earlier, although the difference was not statistically significant (p = 0.09). Acute HBV incidence decreased more in the young adult population in regions that began adolescent vaccination earlier. Maintaining high universal vaccination coverage in the first year of life and in at-risk groups is necessary to achieve HBV elimination by 2030.

Background: The main consequences of chronic hepatitis B virus (HBV) infections are cirrhosis and hepatocellular carcinoma (HCC), both associated with frequent hospitalization. The aim of this study was to analyze the impact of universal HBV vaccination in Spain on chronic HBV-related hospital discharges from 2005 to 2021. Methods: Using data from the Minimum Basic Data Set of the Spanish National Health System, we calculated the hospital discharge rate ratio (HDRR) and 95% confidence interval (CI) values for chronic HBV-related discharges between 2005 and 2021. For comparative purposes, we calculated the HDRR and 95% confidence interval (CI) values for the early (2005–2013) and later (2014–2021) periods and the vaccinated compared with unvaccinated cohorts for the 20–39 age group. Results: The hospital discharge rate per 1,000,000 people was 3.08 in 2005 and 4.50 in 2021 for HCC, and 4.81 in 2005 and 1.92 in 2021 for cirrhosis. Comparing the early and later periods, values were higher for HCC (HDRR 1.13; 95% CI: 1.06–1.20) and lower for cirrhosis (HDRR 0.56; 95% CI: 0.51–0.60). The rate for the 20–39 age group was lower for the vaccinated compared with the unvaccinated cohorts overall (HDRR 0.53; 95% CI: 0.45–0.62), for HCC (HDRR 0.66; 95% CI: 0.53–0.82), and for cirrhosis (HDRR 0.41; 95% CI: 0.33–0.53). Conclusions: This study describes the important impact, after 25 years, of universal HBV vaccination in Spain: cirrhosis hospital discharge rate was reduced, and the vaccinated cohorts, compared with the unvaccinated cohorts in the 20–39 age group, had a lower hospital discharge rate of both HCC and cirrhosis.