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Systems biology is a holistic approach to biological sciences that combines experimental and computational strategies, aimed at integrating information from different scales of biological processes to unravel pathophysiological mechanisms and behaviours. In this scenario, high-throughput technologies have been playing a major role in providing huge amounts of omics data, whose integration would offer unprecedented possibilities in gaining insights on diseases and identifying potential biomarkers. In the present review, we focus on strategies that have been applied in literature to integrate genomics, transcriptomics, proteomics, and metabolomics in the year range 2018–2024. Integration approaches were divided into three main categories: statistical-based approaches, multivariate methods, and machine learning/artificial intelligence techniques. Among them, statistical approaches (mainly based on correlation) were the ones with a slightly higher prevalence, followed by multivariate approaches, and machine learning techniques. Integrating multiple biological layers has shown great potential in uncovering molecular mechanisms, identifying putative biomarkers, and aid classification, most of the time resulting in better performances when compared to single omics analyses. However, significant challenges remain. The high-throughput nature of omics platforms introduces issues such as variable data quality, missing values, collinearity, and dimensionality. These challenges further increase when combining multiple omics datasets, as the complexity and heterogeneity of the data increase with integration. We report different strategies that have been found in literature to cope with these challenges, but some open issues still remain and should be addressed to disclose the full potential of omics integration.

Four percent of the world's population suffers from depression, which is a major public health issue. Medical students are at risk, as their depressive symptoms (DS) prevalence is reported to be approximately 27% worldwide. Since few data on Italian medical students exist, this study aimed to estimate their DS prevalence and assess risk and protective factors. The PRIMES was a multicentre cross-sectional study performed in 12 Italian medical schools. Questionnaires were self-reported and included 30 sociodemographic items and the Beck Depression Inventory-II (BDI-II). The primary outcome was the presence of DS (BDI-II score≥14). The main analyses were chi-squared tests and multivariable logistic regressions with a p-value<0.05 considered significant. The number of collected questionnaires was 2,513 (117 BDI-II incomplete). Females accounted for 61.3% of the respondents, and the median age was 22 years (IQR = 4). The prevalence of DS was 29.5%. Specifically, 14.0% had mild depression, 11.1% had moderate depression, and 4.5% had severe depression. The main risk factors for DS were age, being female, bisexual/asexual orientation, living with partner/housemates, poor economic status (worsened by living far from home), less than 90 min of weekly exercise, relatives with psychiatric disorders, personal chronic disease, judging medical school choice negatively, unsatisfying friendships with classmates, competitive and hostile climate among classmates, thinking that medical school hinders specific activities and being worried about not measuring up to the profession. Protective factors included family cohesion, hobbies, intellectual curiosity as a career motivation and no worries about the future. Italian medical students are at high risk of reporting DS, similar to the global population of medical students'. Medical schools must make efforts to implement preventive and treatment interventions by offering counselling and working on modifiable factors, such as lifestyle and learning climate.

Clinical record (CR) is the primary tool used by healthcare workers (HCWs) to record clinical information and its completeness can help achieve safer practices. CR is the most appropriate source in order to measure and evaluate the quality of care. In order to achieve a safety climate is fundamental to involve a responsive healthcare workforce thorough peer-review and feedbacks. This study aims to develop a peer-review tool for clinical records quality assurance, presenting the seven-year experience in the evolution of it; secondary aims are to describe the CR completeness and HCWs' diligence toward recording information in it. To assess the completeness of CRs a peer-review tool was developed in a large Academic Hospital of Northern Italy. This tool included measurable items that examined different themes, moments and levels of the clinical process. Data were collected every three months between 2010 and 2016 by appointed and trained HCWs from 42 Units; the hospital Quality Unit was responsible for of processing and validating them. Variations in the proportion of CR completeness were assessed using Cochran-Armitage test for trends. A total of 9,408 CRs were evaluated. Overall CR completeness improved significantly from 79.6% in 2010 to 86.5% in 2016 (p<0.001). Doctors' attitude showed a trend similar to the overall completeness, while nurses improved more consistently (p<0.001). Most items exploring themes, moments and levels registered a significant improvement in the early years, then flattened in last years. Results of the validation process were always above the cut-off of 75%. This peer-review tool enabled the Quality Unit and hospital leadership to obtain a reliable picture of CRs completeness, while involving the HCWs in the quality evaluation. The completeness of CR showed an overall positive and significant trend during these seven years.

Cancer aberrant N - and O -linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression. However, the low specificity and toxicity of the existing HBP inhibitors prevented their use for cancer treatment. Here we report the preclinical evaluation of FR054, a novel inhibitor of the HBP enzyme PGM3, with a remarkable anti-breast cancer effect. In fact, FR054 induces in different breast cancer cells a dramatic decrease in cell proliferation and survival. In particular, in a model of Triple Negative Breast Cancer (TNBC) cells, MDA-MB-231, we show that these effects are correlated to FR054-dependent reduction of both N - and O -glycosylation level that cause also a strong reduction of cancer cell adhesion and migration. Moreover we show that impaired survival of cancer cells upon FR054 treatment is associated with the activation of the Unfolded Protein Response (UPR) and accumulation of intracellular ROS. Finally, we show that FR054 suppresses cancer growth in MDA-MB-231 xenograft mice, supporting the advantage of targeting HBP for therapeutic purpose and encouraging further investigation about the use of this small molecule as a promising compound for breast cancer therapy.

Background The treatment of ovarian cancer has significantly improved since the introduction of PARP inhibitors (PARPi), small molecules designed to directly target and kill cancer cells with deficiencies in homologous recombination (HR) pathway. However, nearly half of patients present with HR-proficient tumors, rendering them not eligible for PARPi-based therapies and underscoring the urgent need for alternative treatment strategies. Methods Oxidative metabolism has been altered either by silencing the mitochondria regulator PGC-1β or by using the OXPHOS inhibitor IACS-010759. The metabolic alterations were characterized by seahorse analysis and metabolomic profiling. DNA damage and repair were evaluated by immunofluorescence and confocal analysis. Efficacy and tolerability of the combination of PARP and OXPHOS inhibitors were investigated in preclinical trials employing patient-derived ovarian cancer xenografts. Results Our findings reveal that PGC-1β silencing sensitizes ovarian cancer cells to PARPi by impairing oxidative metabolism, reducing succinate levels and decreasing Fen1 succinylation and SUMOylation. The impairment of these post-translational modifications hinders Fen1 activation and prevents the recruitment of Rad51, resulting in a HR-deficient-like phenotype. The translational relevance of the findings has been validated using the OXPHOS inhibitor IACS-010759, which synergizes with PARPi to inhibit cancer cell proliferation, while sparing normal cells. Furthermore, the combination therapy delays tumor progression in ovarian cancer xenografts not responsive to PARPi, independently from their HR status. Conclusions Targeting mitochondrial metabolism depicts a novel mechanism to modulate DNA repair and enhance PARPi sensitivity. This approach broadens the therapeutic applicability of PARP inhibitors beyond HR-deficient tumors and offers promising avenues to overcome resistance in ovarian cancer treatment.

Background Ten years after the launch of the Okanagan Charter, which called on universities to embed health promotion principles and values into their core strategies, this study investigates how Italian state universities have responded. By analyzing updated strategic plans, we assessed the integration of health and wellbeing principles into their policies, mission, vision, and programming, and identified good practices to be offered to the stakeholders. Methods A deductive content analysis was conducted on the strategic plans of 45 out of 61 Italian state universities. A multidisciplinary team developed a coding framework based on key health promotion themes: participation, wellbeing-centered mission and vision, psycho-physical, social, and organizational wellbeing, sustainability, and equity. Each plan was independently reviewed by three researchers randomly selected out of 12, and findings were synthesized narratively. Results 45 Italian state universities had updated strategic plans, most developed through top-down processes. Only 40% explicitly referenced wellbeing in their mission and vision. While 90% addressed sustainability, mainly energy-related, other aspects like mobility, waste, and food received less attention. Equity was widely considered: 89% promoted inclusion and gender equality, 58% offered tax relief, and 40% provided inmate education. Mental wellbeing was addressed in 64% of plans, social wellbeing in 60%, and healthy lifestyles in 42%. Collaboration with health services was rare, and preventive strategies were limited. The study identified a set of good practices, low-cost, actionable, and community-oriented, that can serve as practical tools to support the implementation of health promotion strategies in universities. Conclusions Italian universities showed a growing but uneven commitment to health promotion. Despite frequent references to wellbeing, its integration remains partial and sectoral. This study identified key areas for improvement, such as participation, and highlighted a selection of good practices. These practices offer actionable and replicable models that, through advocacy, can support the development of healthier, more inclusive, supportive university environments.

Background Increasing work-related stress in academia can have an impact on physical and mental health. The aim of this study was to analyse the coping strategies of staff employed at the University of Udine and to verify whether sociodemographic data, professional position, and the presence of anxiety or depression symptoms are related to the use of different coping strategies. Methods We conducted a cross-sectional study between June and December 2020 using the Brief COPE questionnaire. We correlated coping strategies with professional position, sociodemographic data, and the presence of anxiety or depressive symptoms measured with the Patient Health Questionnaire–9 and the General Anxiety Disorder–7. Results A total of 366 people participated in the study, including 109 junior academics, 146 senior academics, and 111 administrative staff (response rate 23.6%). The three most frequently used coping strategies in terms of approach coping style were planning (6.77 ± 1.41), active coping (6.58 ± 1.45) and acceptance (6.23 ± 1.44). Women were more likely than men to report using approach and avoidant coping strategies ( p  < 0.001). Positive reframing and religion were most commonly used by administrative staff ( p  < 0.05), in contrast to junior academics, who were more likely to use substances and self-blame ( p  < 0.05). Anxiety was found to correlate with self-blame (OR 1.94) as a coping strategy, while depression was associated with venting (OR 2.83), self-blame (OR 3.27), and humor (OR 3.02). Conclusion Identifying profiles of coping strategies can help higher education institutions to implement support strategies for the academic community, ultimately promoting healthier lives and more effective teaching and research. Our study has shown that women and junior academics among staff at the Udine University would benefit from a tailored health promotion intervention that encourages the use of approach coping styles to reduce their risk of developing anxiety and depressive symptoms.

Tumor-associated macrophages (TAMs) represent one of the main tumor-infiltrating immune cell types and are generally categorized into either of two functionally contrasting subtypes, namely classical activated M1 macrophages and alternatively activated M2 macrophages. TAMs showed different activation states that can be represent by the two extremes of the complex profile of macrophages biology, the M1-like phenotype (pro-inflammatory activity) and the M2-like phenotype (anti-inflammatory activity). Based on the tumor type, and grades, TAMs can acquire different functions and properties; usually, the M1-like phenotype is typical of early tumor stages and is associated to an anti-tumor activity, while M2-like phenotype has a pro-inflammatory activity and is related to a poor patients’ prognosis. The classification of macrophages into M1/M2 groups based on well-defined stimuli does not model the infinitely more complex tissue milieu where macrophages (potentially of different origin) would be exposed to multiple signals in different sequential order. This review aims to summarize the recent mass spectrometry-based (MS-based) metabolomics findings about the modifications of metabolism in TAMs polarization in different tumors. The published data shows that MS-based metabolomics is a promising tool to help better understanding TAMs metabolic phenotypes, although it is still poorly applied for TAMs metabolism. The knowledge of key metabolic alterations in TAMs is an essential step for discovering TAMs polarization novel biomarkers and developing novel therapeutic approaches targeting TAM metabolism to repolarize TAMs towards their anti-tumor phenotype.

Oncogenes induce metabolic reprogramming on cancer cells. Recently, G12C KRAS mutation in isogenic NSCLC cell line has been shown to be a key player in promoting metabolic rewiring mainly through the regulation of glutamine metabolism to fuel growth and proliferation. Even though cell lines possessing many of the genetic backgrounds of the primary cancer they derive from could be a valuable pre-clinical model, they do not have the additional complexity present in the whole tumor that impact metabolism. This preliminary study is aimed to explore how cancer cell metabolism in culture might recapitulate the metabolic alterations present in vivo . Our result highlighted that the gross metabolic changes observed in G12C KRAS mutant cells growing in culture were also maintained in the derived xenograft model, suggesting that a simple in vitro cell model can give important insights into the metabolic alterations induced by cancer. This is of relevance for guiding effective targeting of those metabolic traits that underlie tumor progression and anticancer treatment responses.

Background: Despite the availability of thousands of health apps worldwide, when considering those addressing children’s first 1000 days of life, most apps fail to consider the continuity between the prenatal and postnatal stages, and their joint impact on maternal and child health. The reliability, quality, and effectiveness of these apps are largely unknown, and the provided content seems questionable in terms of completeness, updating, and trustworthiness. Objective: This study evaluates available Italian pregnancy and postnatal care apps to highlight the main gaps to be overcome and the resulting future challenges to be met in this mobile health–related field. Methods: A systematic search was conducted on the Apple App Store and Google Play Store, and basic information was collected for all identified apps. After deduplication and further selection based on the exclusion criteria, an in-depth analysis of each app was performed by two researchers independently. A 71-item six-domain questionnaire about the desirable features of apps was used to assess information, functionalities, and technical features, while the Mobile Application Rating Scale (MARS) was employed for app quality evaluation. Results: From an initial sample of 684 apps, 22 were deeply analyzed. Most apps did not fulfill the expectations, as just one achieved 50% of all desirable aspects. Postnatal care and counselling for both the mother and child was the least accomplished domain. Moreover, the quality of app information was generally rated more negatively than the quality of their functionality and esthetic features. The lacking aspects were information about methods for postpartum family planning and birth spacing (1/22, 5%) and immunization (2/22, 9%). Conclusions: The identified gaps could serve as a basis for designing and implementing increasingly high-quality, targeted, and effective apps for pregnancy and postnatal health care, which provide comprehensive, reliable, and evidence-based information, as well as appropriate esthetic and functional characteristics, with relevant implications in terms of maternal and newborn health prevention and promotion.