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Doctoral students experience high rates of mental health distress and dropout; however, the mental health and wellness of engineering doctoral students is understudied. Studies of student persistence, wellness, and success often aggregate fields together, such as by studying all engineering students. Thus, little work has considered the experiences of biomedical engineering (BME) doctoral students, despite differences between doctoral BME research, course content, and career expectations compared with other engineering disciplines. In this qualitative interview case study, we explore stressors present in the BME graduate experience that are unique from engineering students in other disciplines. We analyzed a longitudinal interview study of doctoral engineering students across four timepoints within a single academic year, consisting of a subsample (n = 6) of doctoral students in a BME discipline, among a larger sample of engineering doctoral students (N = 55). BME students in the sample experienced some themes generated from a larger thematic analysis differently compared with other engineering disciplines. These differences are presented and discussed, grounded in a model of workplace stress. BME participants working in labs with biological samples expressed a lack of control over the timing and availability of materials for their research projects. BME participants also had more industry-focused career plans and described more commonly coming to BME graduate studies from other fields (e.g., another engineering major) and struggling with the scope and content of their introductory coursework. A common throughline for the stressors was the impact of the interdisciplinary nature of BME programs, to a greater extent compared with other engineering student experiences in our sample. We motivate changes for researchers, instructors, and policymakers which specifically target BME students and emphasize the importance of considering studies at various unit levels (university department level vs college level vs full institution) when considering interventions targeting student stress and wellness.

Abstract Nucleoside-modified mRNA-LNP vaccines have revolutionized vaccine development against infectious pathogens due to their ability to elicit potent humoral and cellular immune responses. In this article, we present the results of the first norovirus vaccine candidate employing mRNA-LNP platform technology. The mRNA-LNP bivalent vaccine encoding the major capsid protein VP1 from GI.1 and GII.4 of human norovirus, generated high levels of neutralizing antibodies, robust cellular responses, and effectively protected human enteroids from infection by the most prevalent genotype (GII.4). These results serve as a proof of concept, demonstrating that a modified-nucleoside mRNA-LNP vaccine based on norovirus VP1 sequences can stimulate an immunogenic response in vivo and generates neutralizing antibodies capable of preventing viral infection in models of human gastrointestinal tract infection.

Background: Staffing shortages across the healthcare sector pose a threat to the continuity of the Canadian healthcare system in the post-COVID-19 pandemic era. We sought to understand factors associated with turnover intention as well as Canadian healthcare providers’ (HCPs) perspectives and experiences with turnover intention as related to both organizational and professional turnover. Method: A convergent questionnaire mixed-methods design was employed. Descriptive statistics and ordinal logistic regressions were used to analyze quantitative data and ascertain factors associated with turnover intention. Thematic analysis was used to analyze qualitative open-field textbox data and understand HCPs’ perspectives and experiences with turnover intention. Results: Quantitative analyses revealed that 78.6% of HCPs surveyed (N = 398) reported at least a 25% turnover likelihood regarding their organization, with 67.5% reporting at least a 25% turnover likelihood regarding their profession. Whereas regression models revealed the significant impact of years worked, burnout, and organizational support on turnover likelihood for organizations, age, sex, burnout, and organizational support contributed to the likelihood of leaving a profession. Patterns of meaning drawn from participants’ qualitative responses were organized according to the following four themes: (1) Content to stay, (2) Drowning and no one cares, (3) Moral stressors, and (4) Wrestling with the costs and benefits. Conclusions: Many HCPs described weighing the costs and benefits of leaving their organization or profession during the COVID-19 pandemic. Although challenging working conditions, moral stressors, and burnout may play a significant role in HCPs’ experiences of turnover intention, there is ample room to intervene with organizational support.

Abstract Background COVID-19-associated pulmonary aspergillosis (CAPA) is burdened by high mortality. Data are lacking about non-ICU patients. Aims of this study were to: (i) assess the incidence and prevalence of CAPA in a respiratory sub-intensive care unit, (ii) evaluate its risk factors and (iii) impact on in-hospital mortality. Secondary aims were to: (i) assess factors associated to mortality, and (ii) evaluate significant features in hematological patients. Materials and methods This was a single-center, retrospective study of COVID-19 patients with acute respiratory failure. A cohort of CAPA patients was compared to a non-CAPA cohort. Among patients with CAPA, a cohort of hematological patients was further compared to another of non-hematological patients. Results Three hundred fifty patients were included in the study. Median P/F ratio at the admission to sub-intensive unit was 225 mmHg (IQR 155–314). 55 (15.7%) developed CAPA (incidence of 5.5%). Eighteen had probable CAPA (37.3%), 37 (67.3%) possible CAPA and none proven CAPA. Diagnosis of CAPA occurred at a median of 17 days (IQR 12–31) from SARS-CoV-2 infection. Independent risk factors for CAPA were hematological malignancy [OR 1.74 (95%CI 0.75–4.37), p = 0.0003], lymphocytopenia [OR 2.29 (95%CI 1.12–4.86), p = 0.02], and COPD [OR 2.74 (95%CI 1.19–5.08), p = 0.014]. Mortality rate was higher in CAPA cohort (61.8% vs 22.7%, p 65 years resulted a predictor of mortality [OR 5.09 (95% CI 1.20–26.92), p = 0.035]. No differences were observed in hematological cohort. Conclusion CAPA is a life-threatening condition with high mortality rates. It should be promptly suspected, especially in case of hematological malignancy, COPD and lymphocytopenia.

The La Marcelina Formation (LMF) in the southern Deseado Massif area (c. 47° 55? S) represents a 23 m thick sedimentary succession deposited within a low-energy fluvial paleoenvironment. The age of this unit, formerly considered as Eocene due to its palynological assemblage, is adjusted by zircon U-Pb Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) from a sandstone bed at the middle part of the unit. The results reveal a maximum depositional age of ~20 Ma (Early Miocene, Burdigalian). The detrital zircon provenance analysis indicates zircon grains originated mostly in the Jurassic, with limited contributions from the Cretaceous, Permian, and Paleocene. The new age for LMF allows correlating these beds to the upper section of the continental Río Leona Formation in the southern Austral-Magallanes Basin.

Introduction: Exposure to ambient air pollution can worsen cardiovascular disease and increase the risk of stroke, myocardial infarction, and cardiovascular disease mortality. Strategies to reduce air pollution exposure can therefore help prevent cardiovascular morbidity and mortality. This study was conducted to assess the awareness among U.S. adults of the effect of air pollution on cardiovascular health and actions individuals can take to reduce their air pollution exposure. Methods: In May–July 2022, 4,156 adults responded to the summer wave of the 2022 ConsumerStyles survey and self-reported their heart disease status and perceptions, awareness, and behaviors about ambient air pollution and health. In 2023, the data were analyzed to generate weighted population estimates representative of noninstitutionalized U.S. adults. Associations between heart disease and responses about perceptions, awareness, and behaviors were estimated using binomial and multinomial regression methods for weighted data. Results: Overall, 90% of the weighted population estimate of U.S. adults reported that air pollution can impact a person's health, and 44% reported that air pollution can cause or worsen heart disease. Percentages of adults reporting that air pollution can impact a person's health (prevalence ratio=1.09; 95% CI=1.06, 1.12) and that air pollution can cause or worsen heart disease (prevalence ratio=1.28; 95% CI=1.08, 1.51) were higher among adults with than without heart disease. Conclusions: Less than half of U.S. adults are aware that air pollution affects heart disease. Improvements in awareness of the effect of air pollution on cardiovascular health and strategies to reduce exposure could help protect individuals with heart disease.

Abstract Advancements in data acquisition and computational methods are generating a large amount of heterogeneous biomedical data from diagnostic domains such as clinical imaging, pathology, and next-generation sequencing (NGS), which help characterize individual differences in patients. However, this information needs to be available and suitable to promote and support scientific research and technological development, supporting the effective adoption of the precision medicine approach in clinical practice. Digital biobanks can catalyze this process, facilitating the sharing of curated and standardized imaging data, clinical, pathological and molecular data, crucial to enable the development of a comprehensive and personalized data-driven diagnostic approach in disease management and fostering the development of computational predictive models. This work aims to frame this perspective, first by evaluating the state of standardization of individual diagnostic domains and then by identifying challenges and proposing a possible solution towards an integrative approach that can guarantee the suitability of information that can be shared through a digital biobank. Our analysis of the state of the art shows the presence and use of reference standards in biobanks and, generally, digital repositories for each specific domain. Despite this, standardization to guarantee the integration and reproducibility of the numerical descriptors generated by each domain, e.g. radiomic, pathomic and -omic features, is still an open challenge. Based on specific use cases and scenarios, an integration model, based on the JSON format, is proposed that can help address this problem. Ultimately, this work shows how, with specific standardization and promotion efforts, the digital biobank model can become an enabling technology for the comprehensive study of diseases and the effective development of data-driven technologies at the service of precision medicine.

We investigated the effect of estradiol add-back therapy (EAT) on brain activation related to cognitive function and affect in addition to putative changes in gray and white matter volume in testosterone depleted participants with prostate cancer. We conducted a randomized controlled, double-blinded trial in which 40 patients received 0.9 mg of transdermal estradiol per day for 6 months or matched placebo. Anatomical MRI and three functional MRI (fMRI) scans were obtained for the emotion recognition task, verbal memory task, and visuospatial memory task. Activation in corresponding cognitive and affective brain networks was demonstrated for all tasks. Longitudinally, there was no difference in brain activation, reaction time, or accuracy in response to the fMRI tasks between the EAT group and placebo group at 6 months. In addition, there was no detectable change in whole-brain gray or white matter volume or in hippocampal volume between the two groups after 6 months. This study supports earlier findings that EAT does not improve verbal memory or affect and has no immediate effect on hippocampal volume in testosterone depleted patients with prostate cancer.

Background: Hashimoto’s thyroiditis (HT) is a common autoimmune thyroid disorder characterized by elevated anti-thyroid peroxidase (A-TPO) antibodies. HT frequently coexists with other autoimmune conditions, which are marked by organ-specific and non-organ-specific autoantibodies, reflecting a deregulated immune response. However, the burden and clinical significance of these circulating autoantibodies in adult patients with HT remains unclear. Methods: A cross-sectional study was conducted at the University Hospital “R. Dulbecco” in Catanzaro, Italy, from November 2023 to May 2024, involving 200 euthyroid adults. The study population comprised 100 A-TPO-positive HT patients and 100 A-TPO-negative controls, matched for age and sex. Laboratory assessments included thyroid function tests and detection of autoantibodies [e.g., antinuclear antibodies (ANA), anti-parietal cell antibodies (APCA), and anti-neutrophil cytoplasmic antibodies (ANCA)]. Cytokine profiles were also measured using sensitive chemiluminescent multi-array technology. Results: HT patients were predominantly female (77.0%) with a median age of 56 years. Compared to controls, HT patients had higher median thyroid stimulating hormone (TSH) levels (2.215 vs. 1.705 μIU/mL, p = 0.025). Circulating autoantibodies were more prevalent in the HT group, with higher rates of APCA positivity (16.3% vs. 4.1%, p = 0.008) and atypical ANCA positivity (27.3% vs. 10.2%, p = 0.003). This suggests an increased risk for autoimmune gastritis and systemic inflammation. Additionally, HT patients with positive atypical ANCA showed elevated inflammatory cytokines, particularly interleukin-1 alpha (IL-1α), in female patients (p = 0.035). Conclusions: HT is significantly associated with a higher prevalence of circulating autoantibodies, such as APCA and atypical ANCA, which may indicate a heightened risk for autoimmune gastritis and broader autoimmune involvement. Detecting these autoantibodies in HT patients could serve as markers for more severe autoimmune dysfunction. These findings emphasize the need for proactive screening, especially in older patients and those with elevated A-TPO levels. Further research is essential to better understand the clinical implications and develop targeted management strategies for these patients.

Background: Mental health for engineering undergraduates is an urgent topic for engineering educators. Narratives of engineering education requiring suffering may create or exacerbate problematic perceptions around stress and mental health in engineering. This study explored the roles of stress and mental health in engineering culture. We sought to explore: (1) how engineering students describe their experiences related to stress and mental health and (2) norms and expectations engineering students share about stress and mental health. Qualitative interview data were collected from 30 students who had previously responded to a college-wide survey. Results: Codes related to experiences with stress and mental health in engineering were organized in a bioecological systems model and analyzed for emergent themes depicting engineering culture. The study identified three themes related to stress and mental health in engineering culture: (1) engineering workload as a defining stressor, (2) specific barriers that prevent engineering students from seeking help for mental health concerns, and (3) reliance on peers to cope with stress and mental health distress. Conclusions: Our analysis provided insight into how engineering students perceive norms around stress and mental health in engineering and how this impacts help-seeking for mental health challenges. These findings have important implications for developing interventions and positive cultures that support student mental health.

Recent major disruptions such as natural disasters, geopolitical tensions, Covid-19 pandemic have led supply chain managers to rethink strategies for achieving significant levels of sustainability and resilience. At the same time, new digital technologies are offering significant opportunities to increase company performance, while maintaining a high level of customer service. In this challenging context, the Supply Chain Digital Twin (SCDT) represents an emerging and promising concept, which deserves to be explored. In this paper, a holistic and cyclical methodology, based on simulation, is proposed to enable and exploit the SCDT Paradigm, with the main aim to increase sustainability and resilience of the chains. The proposed methodology is successfully tested and validated on a real case study in the agri-food sector, through the use of the anyLogistix software. The results return valuable information on the level of resilience of the supply chain in the face of any considered disruption and provide useful managerial insights on the actions to be taken to improve some performance indicators.

BackgroundPaediatric acute B-cell lymphoblastic leukaemia is the most common cancer of the paediatric age. Although the advancement of scientific and technological knowledge has ensured a huge step forward in the management of this disease, there are 15%–20% cases of recurrence leading to serious complications for the patient and sometimes even death. It is therefore necessary to identify new and increasingly personalised biomarkers capable of predicting the degree of risk of B-ALL in order to allow the correct management of paediatric leukaemia patients.MethodsStarting from our previously published results, we validate the expression level of LINC00958 in a cohort of 33 B-ALL and 9 T-ALL childhood patients, using in-silico public datasets as support. Expression levels of LINC00958 in B-ALL patients stratified by risk (high risk vs. standard/medium risk) and who relapsed 3 years after the first leukaemia diagnosis were also evaluated.ResultsWe identified the lncRNA LINC00958 as a biomarker of B-ALL, capable of discriminating B-ALL from T-ALL and healthy subjects. Furthermore, we associated LINC00958 expression levels with the disease risk classification (high risk and standard risk). Finally, we show that LINC00958 can be used as a predictor of relapses in patients who are usually stratified as standard risk and thus not always targeted for marrow transplantation.ConclusionsOur results open the way to new diagnostic perspectives that can be directly used in clinical practice for a better management of B-ALL paediatric patients.

Significant efforts have focused on identifying targetable genetic drivers that support the growth of solid tumors and/or increase metastatic ability. During tumor development and progression to metastatic disease, physiological and pharmacological selective pressures influence parallel adaptive strategies within cancer cell sub-populations. Such adaptations allow cancer cells to withstand these stressful microenvironments. This Darwinian model of stress adaptation often prevents durable clinical responses and influences the emergence of aggressive cancers with increased metastatic fitness. However, the mechanisms contributing to such adaptive stress responses are poorly understood. We now demonstrate that the p66ShcA redox protein, itself a ROS inducer, is essential for survival in response to physiological stressors, including anchorage independence and nutrient deprivation, in the context of poor outcome breast cancers. Mechanistically, we show that p66ShcA promotes both glucose and glutamine metabolic reprogramming in breast cancer cells, to increase their capacity to engage catabolic metabolism and support glutathione synthesis. In doing so, chronic p66ShcA exposure contributes to adaptive stress responses, providing breast cancer cells with sufficient ATP and redox balance needed to withstand such transient stressed states. Our studies demonstrate that p66ShcA functionally contributes to the maintenance of aggressive phenotypes and the emergence of metastatic disease by forcing breast tumors to adapt to chronic and moderately elevated levels of oxidative stress.

Craniosynostoses (CRS) are caused by the premature fusion of one or more cranial sutures, with isolated nonsyndromic CRS accounting for most of the clinical manifestations. Such premature suture fusion impacts both skull and brain morphology and involves regions far beyond the immediate area of fusion. The combined use of different neuroimaging tools allows for an accurate depiction of the most prominent clinical–radiological features in nonsyndromic CRS but can also contribute to a deeper investigation of more subtle alterations in the underlying nervous tissue organization that may impact normal brain development. This review paper aims to provide a comprehensive framework for a better understanding of the present and future potential applications of neuroimaging techniques for evaluating nonsyndromic CRS, highlighting strategies for optimizing their use in clinical practice and offering an overview of the most relevant technological advancements in terms of diagnostic performance, radiation exposure, and cost-effectiveness.

Background: Obesity constitutes a chronic, low-grade inflammatory status that predisposes people to the development of insulin resistance and cardiometabolic complications. Hypoxia, a main pathological feature of visceral fat in obese individuals, has been shown to affect the secretome of murine 3T3-L1 adipose cells, causing the upregulation of prothymosin-alpha (ProT-α), which is a protein with immunomodulatory functions that was originally found in the thymus. The aim of this case–control observational study was to measure the circulating levels of ProT-α in obese and lean individuals and determine whether such levels are correlated with inflammatory and metabolic parameters. Methods: Sixty-one obese patients (BMI ≥ 30 Kg/m2) and fifty-one age-matched, lean controls (BMI 18.5–24.9 Kg/m2) were recruited in the Endocrinology Unit (“Mater-Domini”) of the University Hospital of Catanzaro, Italy. The exclusion criteria included affliction with acute and systemic inflammatory states (i.e., leukocytosis), recent infectious diseases or vaccinations, obesity complications (i.e., type 2 diabetes mellitus and cardiovascular diseases), hepatic or renal failure, pregnancy and lactation, cancer, use of drugs or alcohol, and smoking. Apart from routine biochemical determinations, serum samples were screened for the presence of ProT-α using an ELISA method and for the presence of a panel of inflammatory cytokines and growth factors via a multiparametric chemiluminescence micro-array. Results: Between the age-matched groups, no statistically significant differences were shown in relation to fasting glucose, HbA1c, liver function tests, lipid profiles, circulating interleukins (IL)-1α, -1β, -2, -4, -8, and -10, MCP-1, TNF-α, VEGF and EGF. Instead, significantly higher median levels were observed in obese patients vs. lean controls with respect to fasting insulin levels (p < 0.001), a classic insulin resistance marker, and IL-6 (p = 0.004). In addition, ProT-α levels were significantly and considerably higher in obese patients compared to lean controls (median ProT-α, 600.0 vs. 411.5 pg/mL, p = 0.004) and showed a moderate to strong positive relationship with fasting insulin levels and selected cytokines (i.e., TNF-α and IL-8). Conclusions: An increase in circulating levels of ProT-α is linked with obesity and can be detected before any clinical cardiometabolic complications develop. ProT-α may represent a novel and sensitive biomarker for inflammation and insulin resistance in obese individuals.

Abstract Background Increasing evidence links the gut microbiota (GM) to Alzheimer’s disease (AD) but the mechanisms through which gut bacteria influence the brain are still unclear. This study tests the hypothesis that GM and mediators of the microbiota-gut-brain axis (MGBA) are associated with the amyloid cascade in sporadic AD. Methods We included 34 patients with cognitive impairment due to AD (CI-AD), 37 patients with cognitive impairment not due to AD (CI-NAD), and 13 cognitively unimpaired persons (CU). We studied the following systems: (1) fecal GM, with 16S rRNA sequencing; (2) a panel of putative MGBA mediators in the blood including immune and endothelial markers as bacterial products (i.e., lipopolysaccharide, LPS), cell adhesion molecules (CAMs) indicative of endothelial dysfunction (VCAM-1, PECAM-1), vascular changes (P-, E-Selectin), and upregulated after infections (NCAM, ICAM-1), as well as pro- (IL1β, IL6, TNFα, IL18) and anti- (IL10) inflammatory cytokines; (3) the amyloid cascade with amyloid PET, plasma phosphorylated tau (pTau-181, for tau pathology), neurofilament light chain (NfL, for neurodegeneration), and global cognition measured using MMSE and ADAScog. We performed 3-group comparisons of markers in the 3 systems and calculated correlation matrices for the pooled group of CI-AD and CU as well as CI-NAD and CU. Patterns of associations based on Spearman’s rho were used to validate the study hypothesis. Results CI-AD were characterized by (1) higher abundance of Clostridia_UCG-014 and decreased abundance of Moryella and Blautia (p

Abstract Background Mental health for engineering undergraduates is an urgent topic for engineering educators. Narratives of engineering education requiring suffering may create or exacerbate problematic perceptions around stress and mental health in engineering. This study explored the roles of stress and mental health in engineering culture. We sought to explore: (1) how engineering students describe their experiences related to stress and mental health and (2) norms and expectations engineering students share about stress and mental health. Qualitative interview data were collected from 30 students who had previously responded to a college-wide survey. Results Codes related to experiences with stress and mental health in engineering were organized in a bioecological systems model and analyzed for emergent themes depicting engineering culture. The study identified three themes related to stress and mental health in engineering culture: (1) engineering workload as a defining stressor, (2) specific barriers that prevent engineering students from seeking help for mental health concerns, and (3) reliance on peers to cope with stress and mental health distress. Conclusions Our analysis provided insight into how engineering students perceive norms around stress and mental health in engineering and how this impacts help-seeking for mental health challenges. These findings have important implications for developing interventions and positive cultures that support student mental health.

Finalizada la Segunda Guerra Mundial, inició un periodo que estuvo orientado a la reorganización del nuevo orden mundial, no solo desde el punto de vista geopolítico, sino también desde el lado de la economía y del escenario de las relaciones internacionales. En ello contribuyó el acuerdo de Bretton Woods (1944), (quien da origen al FMI y al BIRF), cuyas negociaciones culminaron en la Carta de la Habana (1948). Su fruto fue el GATT, el cual sentó las bases para reglar las barreras al comercio internacional y su multilateralización. Acompañado por un importante crecimiento del comercio internacional y el predominio estadounidense, Europa comenzó su recuperación y dio inicio a su proceso de integración económica. Primero con la CECA por el Tratado de París y luego, con la firma de los Tratados de Roma de 1957, se originó la Comunidad Económica Europea. Fueron estos algunos de los hitos que marcaron las bases del sistema económico mundial de posguerra. América Latina no se mantuvo al margen de esta nueva tendencia e inició un proceso de cambio impulsado por la CEPAL como promotor de las ideas sobre el desarrollo y la integración que llevaron a conformar su propio espacio regional: la Asociación Latinoamericana de Libre Comercio (ALALC) con la firma del Tratado de Montevideo de 1960.

IntroductionDiffusion Tensor Imaging (DTI) has revealed measurable changes in the brains of patients with persistent post-concussive syndrome (PCS). Because of inconsistent results in univariate DTI metrics among patients with mild traumatic brain injury (mTBI), there is currently no single objective and reliable MRI index for clinical decision-making in patients with PCS.PurposeThis study aimed to evaluate the performance of a newly developed PCS Index (PCSI) derived from machine learning of multiparametric magnetic resonance imaging (MRI) data to classify and differentiate subjects with mTBI and PCS history from those without a history of mTBI.Materials and methodsData were retrospectively extracted from 139 patients aged between 18 and 60 years with PCS who underwent MRI examinations at 2 weeks to 1-year post-mTBI, as well as from 336 subjects without a history of head trauma. The performance of the PCS Index was assessed by comparing 69 patients with a clinical diagnosis of PCS with 264 control subjects. The PCSI values for patients with PCS were compared based on the mechanism of injury, time interval from injury to MRI examination, sex, history of prior concussion, loss of consciousness, and reported symptoms.ResultsInjured patients had a mean PCSI value of 0.57, compared to the control group, which had a mean PCSI value of 0.12 (p = 8.42e-23) with accuracy of 88%, sensitivity of 64%, and specificity of 95%, respectively. No statistically significant differences were found in the PCSI values when comparing the mechanism of injury, sex, or loss of consciousness.ConclusionThe PCSI for individuals aged between 18 and 60 years was able to accurately identify patients with post-concussive injuries from 2 weeks to 1-year post-mTBI and differentiate them from the controls. The results of this study suggest that multiparametric MRI-based PCSI has great potential as an objective clinical tool to support the diagnosis, treatment, and follow-up care of patients with post-concussive syndrome. Further research is required to investigate the replicability of this method using other types of clinical MRI scanners.

Abstract Background Long non-coding RNAs are RNAs longer than 200 bps that do not encode any proteins and are able to alter gene expression by acting on different steps of regulation, including DNA methylation and chromatin structure. They represent a class of biomarkers of crescent interest in the hematologic and oncologic fields. Recent studies showed that the expression levels of specific lncRNAs correlate with the prognosis of paediatric patients with Acute Lymphoblastic Leukaemia. Methods We used NGS approaches to analyse the transcriptome of 9 childhood B-ALL patients and 6 childhood T-ALL patients, in comparison with B and T healthy lymphocytes from cord blood. We validate our findings both ex vivo, in a different cohort of 10 B-ALL and 10 T-ALL patients, and in silico using public datasets. Results We characterised the lncRNA landscape for B-ALL, T-ALL, healthy B, and T cell progenitors. From the characterised signature, we selected candidate lncRNAs able to discriminate not only B-ALL and T-ALL from healthy subjects but also between the two types of leukaemia, and subsequently validated their potential as a diagnostic tool in an additional cohort of paediatric patients. We confirmed our finding with open access transcriptomic data, comparing ALL lncRNAs with AML lncRNA landscape as well. Finally, expression correlation analyses of T-ALL selected lncRNA biomarkers suggested a possible role in lymphocyte activation and the β-catenin signalling pathway for AC247036.1 and involvement in hedgehog signalling for HHIP-AS1. Conclusions Our work identified a lncRNA signature discriminating paediatric B-ALL and T-ALL from healthy subjects, between them and from AML. This study provides the keystone to future clinical studies determining the theragnostic value of the characterised long non coding transcriptome panorama in a clinical setting for childhood patient management.

Abstract Behavioral assessments during the clinical evaluation in prolonged disorders of consciousness patients could be not sufficient for a correct diagnosis and prognostication. To this aim, we used an innovative approach, involving the ultra-sensitive determination of biological markers, correlating them with imaging parameters to investigate the prolonged disorders of consciousness (pDoC).We assessed the serum concentration of neurofilament light chain(NF-L) and glial fibrillary acidic protein (GFAP) in pDoC (n = 16), and healthy controls (HC, n = 6) as well as several clinical imaging parameters such as Fractional Anisotropy (FA), Whole Brain SUV, and White Matter Hyperintensities volumes (WMH) using PET-MRI acquisition. As for differential diagnosis task, only the imaging WMH volume was able to discriminate between vegetative state/unresponsive wakefulness syndrome (VS/UWS), and minimally conscious state (MCS) patients (p-value

Objectives Workers in the construction industry have been exposed to asbestos in various occupations. In Italy, a National Mesothelioma Registry has been implemented more than 20 years ago. Using cases selected from this registry and exploiting existing control data sets, we estimated relative risks for pleural mesothelioma (PM) among construction workers.Design Case–control study.Setting Cases from the National Mesothelioma Registry (2000–2018), controls from three previous case–control studies.Methods We selected male PM incident cases diagnosed in 2000–2018. Population controls were taken from three studies performed in six Italian regions within two periods (2002–2004 and 2012–2016). Age-adjusted and period-adjusted unconditional logistic regression models were fitted to estimate odds ratios (OR) for occupations in the construction industry. We followed two approaches, one (primary) excluding and the other (secondary) including subjects employed in other non-construction blue collar occupations for >5 years. For both approaches, we performed an overall analysis including all cases and, given the incomplete temporal and geographic overlap of cases and controls, three time or/and space restricted sensitivity analyses.Results The whole data set included 15 592 cases and 2210 controls. With the primary approach (4797 cases and 1085 controls), OR was 3.64 (2181 cases) for subjects ever employed in construction. We found elevated risks for blue-collar occupations (1993 cases, OR 4.52), including bricklayers (988 cases, OR 7.05), general construction workers (320 cases, OR 4.66), plumbers and pipe fitters (305 cases, OR 9.13), painters (104 cases, OR 2.17) and several others. Sensitivity analyses yielded very similar findings. Using the secondary approach, we observed similar patterns, but ORs were remarkably lower.Conclusions We found markedly increased PM risks for most occupations in the construction industry. These findings are relevant for compensation of subjects affected with mesothelioma in the construction industry.

Históricamente la integración latinoamericana es el resultado o fruto de un proceso de corrientes ideológicas que han sido desplegadas a través del tiempo. El fenómeno integracionista latinoamericano que desde mediados del Siglo XX ha seguido un camino hacia una idea de desarrollo de la región, no arrojó resultados homogéneos y continuos a partir de la inexistencia de un escenario plácido, ya sea por la afluencia de factores endógenos o exógenos inherentes a los diferentes procesos. Desde la Asociación Latinoamericana de Libre Comercio (ALALC) y el Mercado Común Centroamericano (MCCA), creados ambos en los años sesenta bajo el marco normativo del GATT y el paradigma europeo de integración, se buscaba, a partir de las ideas cepalinas, generar un espacio de desarrollo mediante la ampliación de sus mercados e industrialización para lograr luego un mejor posicionamiento de la región en su inserción internacional. Es así como el camino recorrido ha sido sinuoso y marcado por situaciones de tensión que han determinado marchas y contramarchas atribuidos a factores endógenos: políticos e institucionales, por las interrupciones de gobiernos democráticos que socavaron la voluntad política necesaria para conformar bloques, el carácter intergubernamental de las instituciones con un marcado presidencialismo, cambios de gobiernos e ideologías que implicaron variaciones de actitudes frente a los socios y en sus políticas exteriores de inserción como también en los modelos de desarrollo adoptados. Asimismo, incidieron factores exógenos: modificaciones en las relaciones y posturas de los países centrales respecto a la región, la irrupción de actores de importancia a nivel mundial como China (convertida en uno de los principales socios de la región) con su conflicto geopolítico con EE.UU, conflictos bélicos de distinta naturaleza con efectos migracionales al resto del mundo e incluso la amenaza pandémica del COVID-19.

The treatment of deep-seated tumours with electrons of very high energies (VHEE, 70–150 MeV) has already been explored in the past, suggesting that a dosimetric coverage comparable with state-of-the-art proton (PT) or photon radiotherapy (RT) could be achieved with a large (> 10) number of fields and high electron energy. The technical and economical challenges posed by the deployment of such beams in treatment centres, together with the expected small therapeutic gain, prevented the development of such technique. This scenario could radically change in the light of recent developments that occurred in the compact, high-gradient, electron acceleration technology and, additionally, of the experimental evidence of the sparing of organs at risk achieved in ultra-high dose rate irradiation, also referred to as FLASH. Electrons with the energy required to treat intracranial lesions could be provided, at dose rates compatible with what is needed to trigger the FLASH effect, by accelerators that are a few metres long, and the organ sparing could be exploited to significantly simplify the irradiation geometry, decreasing the number of fields needed to treat a patient. In this paper, the case of two patients affected by a chordoma and a meningioma, respectively, treated with protons in Trento (IT) is presented. The proton plans have been compared with VHEE plans and X-ray intensity-modulated radiotherapy (IMRT) plans. The VHEE plans were first evaluated in terms of physical dose distribution and then assuming that the FLASH regimen can be achieved. VHEE beams demonstrated their potential in obtaining plans that have comparable tumour coverage and organs at risk sparing when benchmarked against current state-of-the-art IMRT and PT. These results were obtained with a number of explored fields that was in the range between 3 and 7, consistent with what is routinely performed in IMRT and PT conventional irradiations. The FLASH regimen, in all cases, showed its potential in reducing damage to the organs placed nearby the target volume, allowing, particularly in the chordoma case where the irradiation geometry is more challenging, a better tumour coverage with respect to the conventional treatments.

In recent years, the field of metal-halide perovskite emitters has rapidly emerged as a new community in solid-state lighting. Their exceptional optoelectronic properties have contributed to the rapid rise in external quantum efficiencies (EQEs) in perovskite light-emitting diodes (PeLEDs) from

The aim of this study is to evaluate the effects of orthodontic traction, by means of light and controlled forces, on root length in impacted maxillary canines and physiologically erupted maxillary canines. Disinclusion of impacted maxillary canines is a frequent procedure in orthodontics due to their higher incidence of impaction. The effects of orthodontic traction, by means of light and controlled forces, can lead to a resorption of the root length in impacted and physiologically erupted teeth. Therefore, apical root resorption is a common phenomenon that must be taken into consideration. Apical root resorption measurements were taken using pre-treatment CBCTs and pre-treatment and post-treatment digital panoramic radiographs of 52 patients who underwent fixed-appliance treatment by using light and controlled orthodontic forces. The experimental group consisted of 26 patients with one impacted maxillary canine. The control group consisted of 26 patients without any impaction. Apical root resorption was calculated from root lengths before and after orthodontic treatment. In the experimental group, impacted canines with incomplete apical formation underwent root elongation, while impacted canines with completed root formation went through apical root resorption. The latter showed a slightly greater apical root resorption (0.2 mm) compared to the control group (95% confidence interval; p = 0.04). The extent of root resorption of impacted canines was significantly higher than that of physiologically erupted ones. However, this differential resorption did not compromise the structural and functional integrity of the involved teeth. The orthodontic treatment performed with light and controlled forces is, therefore, a procedure to be considered acceptable and safe.

Introduction: Differentiated thyroid carcinoma (DTC) is frequently found in conjunction with autoimmune thyroid disorders, particularly Hashimoto’s thyroiditis (HT). This study investigates the impact of coexisting HT on the persistence of an indeterminate response to therapy due to positive anti-thyroglobulin antibodies (AbTg), measured via competitive immunoassay, in a consecutive patient series from Calabria, Southern Italy. Methods: This retrospective longitudinal study analyzed 259 consecutive DTC patients managed at the Endocrinology Unit of Renato Dulbecco Hospital (Catanzaro, Italy) up to 2023. Patients with medullary and undifferentiated thyroid carcinoma, partial thyroidectomy, less than six months of post-operative monitoring, or missing clinical data were excluded. Demographic information, histological findings, initial tumor stage, and ATA risk category were collected. The response to therapy was assessed based on ATA guidelines. Results: Among the 259 patients, 29% had coexisting HT. Patients with HT exhibited distinct characteristics: a higher proportion of females (87.0% vs. 74.7%), a shorter post-operative monitoring duration (median 3 vs. 5 years), and a higher prevalence of papillary thyroid carcinoma (PTC) (97.4% vs. 86.3%). The tumor size, lymph node involvement, and distant metastasis were similar between the groups, with patients without HT having a higher incidence of extrathyroidal tumor extension. However, the initial TNM stage and ATA risk category did not differ significantly. At the six-month follow-up, HT patients showed a higher rate of indeterminate responses, primarily due to positive AbTg. After 12 months, the response categories aligned, with decreasing AbTg levels in the HT group. After 24 months, most patients with long-term follow-up demonstrated an excellent response to DTC therapy, irrespective of HT coexistence. Conclusions: While HT does not worsen DTC prognosis, it may result in indeterminate responses. AbTg measurements in the peri-operative period should be encouraged to facilitate post-operative monitoring, emphasizing the importance of using standardized assays. Further research in larger populations with extended follow-up is needed to comprehensively understand the HT-DTC relationship.