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Abstract Objectives The control chart is a classic statistical technique in epidemiology for identifying trends, patterns, or alerts. One meaningful use is monitoring and tracking Infant Mortality Rates, which is a priority both domestically and for the World Health Organization, as it reflects the effectiveness of public policies and the progress of nations. This study aims to evaluate the applicability and performance of this technique in Brazilian cities with different population sizes using infant mortality data. Results In this article, we evaluate the effectiveness of the statistical process control chart in the context of Brazilian cities. We present three categories of city groups, divided based on population size and classified according to the quality of the analyses when subjected to the control method: consistent, interpretable, and inconsistent. In cities with a large population, the data in these contexts show a lower noise level and reliable results. However, in intermediate and small-sized cities, the technique becomes limited in detecting deviations from expected behaviors, resulting in reduced reliability of the generated patterns and alerts.

Abstract Resistive Random Access Memory (RRAM) has gained considerable momentum due to its non-volatility and energy efficiency. Material and device scientists have been proposing novel material stacks that can mimic the “ideal memristor” which can deliver performance, energy efficiency, reliability and accuracy. However, designing RRAM-based systems is challenging. Engineering a new material stack, designing a device, and experimenting takes significant time for material and device researchers. Furthermore, the acceptability of the device is ultimately decided at the system level. We see a gap here where there is a need for facilitating material and device researchers with a “push button” modeling framework that allows to evaluate the efficacy of the device at system level during early device design stages. Speed, accuracy, and adaptability are the fundamental requirements of this modelling framework. In this paper, we propose a digital twin (DT)-like modeling framework that automatically creates RRAM device models from device measurement data. Furthermore, the model incorporates the peripheral circuit to ensure accurate energy and performance evaluations. We demonstrate the DT generation and DT usage for multiple RRAM technologies and applications and illustrate the achieved performance of our GPU implementation. We conclude with the application of our modeling approach to measurement data from two distinct fabricated devices, validating its effectiveness in a neural network processing an Electrocardiogram (ECG) dataset and incorporating Fault Aware Training (FAT).

Understanding the dynamics of physiological changes involved in the acclimation responses of plants after their exposure to repeated cycles of water stress is crucial to selecting resilient genotypes for regions with recurrent drought episodes. Under such background, we tried to respond to questions as: (1) Are there differences in the stomatal-related and non-stomatal responses during water stress cycles in different clones of Coffea canephora Pierre ex A. Froehner? (2) Do these C. canephora clones show a different response in each of the two sequential water stress events? (3) Is one previous drought stress event sufficient to induce a kind of “memory” in C. canephora? Seven-month-old plants of two clones (’3V’ and ‘A1’, previously characterized as deeper and lesser deep root growth, respectively) were maintained well-watered (WW) or fully withholding the irrigation, inducing soil water stress (WS) until the soil matric water potential (Ψmsoil) reached ≅ −0.5 MPa (−500 kPa) at a soil depth of 500 mm. Two sequential drought events (drought-1 and drought-2) attained this Ψmsoil after 19 days and were followed by soil rewatering until a complete recovery of leaf net CO2 assimilation rate (Anet) during the recovery-1 and recovery-2 events. The leaf gas exchange, chlorophyll a fluorescence, and leaf reflectance parameters were measured in six-day frequency, while the leaf anatomy was examined only at the end of the second drought cycle. In both drought events, the WS plants showed reduction in stomatal conductance and leaf transpiration. The reduction in internal CO2 diffusion was observed in the second drought cycle, expressed by increased thickness of spongy parenchyma in both clones. Those stomatal and anatomical traits impacted decreasing the Anet in both drought events. The ‘3V’ was less influenced by water stress than the ‘A1’ genotype in Anet, effective quantum yield in PSII photochemistry, photochemical quenching, linear electron transport rate, and photochemical reflectance index during the drought-1, but during the drought-2 event such an advantage disappeared. Such physiological genotype differences were supported by the medium xylem vessel area diminished only in ‘3V’ under WS. In both drought cycles, the recovery of all observed stomatal and non-stomatal responses was usually complete after 12 days of rewatering. The absence of photochemical impacts, namely in the maximum quantum yield of primary photochemical reactions, photosynthetic performance index, and density of reaction centers capable of QA reduction during the drought-2 event, might result from an acclimation response of the clones to WS. In the second drought cycle, the plants showed some improved responses to stress, suggesting “memory” effects as drought acclimation at a recurrent drought.

Abstract Purpose The most harmful atmospheric pollutant for human health is particulate matter (PM). We analyzed the correlation between short-term lag exposure to PM10 and PM2.5, salivary cortisol and TNF-α level, and methylation levels of the TNF-α promoter. Methods A pilot study including 20 subjects. Eight salivary samples for each subject at various times of the day were collected for comparing cortisol levels and TNFα detection. TNFα promoter methylation levels on salivary DNA were analyzed. Regression analyses were performed using generalized linear mixed models between the different outcomes and 4, 3, 2 and 1 day’s lag values of PM10/PM2.5.Generalized additive mixed model (GAMM) was used to evaluate any potential deviation from linearity. Results Area under the curve with respect to the ground (AUCg) showed a statistically positive association with 4-, 3-, 2-, and 1-day lag of exposure to PM10. Area under the curve with respect to the increase (AUCi) showed a statistically negative association with 4-, 3- and 1-day lag of exposure to PM10. TNFα showed statistically significant association with both exposures, PM10 and PM2.5, at 4-, 3-, 2-, and 1-day lag. Conclusions Regarding cortisol levels there is an increase of overall hormone levels but a less dynamism of the system to answer to external stressors. Increase of TNF-α may reflect increased levels of oxidative stress and inflammation due to pollution exposure.

Abstract Background Preterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP. Methods BORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions. Results Results in the intention-to-treat and per-protocol analysis are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBCs or A-RBCs. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06–2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk. Conclusions The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP. Trial registration Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212.

Discourses of global education, citizenship and competence have been characterising the higher education literature in recent years. The COVID-19 pandemic has both heightened the relevance of global citizenship education and presented new challenges as educators and students continue to grapple with the lasting impact and implications. This paper presents the findings of a research study which looked at the perceived learning outcomes of a "virtual exchange" project which addressed issues relevant to global citizenship, involving students in European and Southern Mediterranean countries in online dialogue programmes. The study used quantitative and qualitative approaches to the analysis of responses to open survey questions using the quantitative tool IRAMUTEQ (Sbalchiero & Tuzzi, 2016) and focus groups. Participants perceived that their learning was happening above all through their encounters and discussions with people from different backgrounds. They reported learning to listen actively and carefully, to accept and/or respect different opinions and experiences. The findings open up possibilities for how higher education institutions might engage students in online transnational and global learning experiences--which can contribute to thinking about renewing education and societies in a post-pandemic world.

This study critically examines the public’s perception of Florence Nightingale’s legacy through a critical discourse analysis (CDA) of digital media, specifically podcasts and YouTube. Nightingale, who is often remembered as “The Lady with the Lamp”, holds a complex identity within modern narratives that is celebrated for her pioneering contributions to nursing and public health, even if there are some disagreements about her, given the colonialist setting that may have shaped some of her opinions and decisions. This research employed CDA to analyze 25 podcasts and 18 YouTube videos, which were systematically included according to a priori inclusion criteria. The study synthesized how these media products portray Nightingale and, by extension, shape public discourse about the nursing profession. The findings reveal five thematic representations of Nightingale: as a legendary figure, a modern feminist, a dedicated statistician, a pioneer in public health, and a pivotal STEM contributor. These portrayals challenge traditional nursing stereotypes by emphasizing Nightingale’s role as a rigorous scientist and reformer, suggesting broader perceptions of nurses that encompass leadership, analytical skills, and strategic thinking. The study supports the hypothesis that digital narratives significantly influence the public’s understanding and appreciation of nursing, advocating for a more nuanced professional identity that integrates traditional caregiving roles with critical and analytical capabilities.

Background/Aims The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD). Methods This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity-specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD, and non-MAFLD HCC. Results 22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% confidence interval [CI] 34.5–63.0%) and 12.4% (95% CI 8.3–17.3%), respectively. In HCC due to chronic hepatitis B, C, and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI 30.2–50.3%), 54.1% (95% CI 40.4–67.6%) and 64.3% (95% CI 52.7–75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC. Conclusions MAFLD is common as a sole aetiology, but more so as a co-factor in mixed-aetiology HCC, supporting the use of positive diagnostic criteria.

Background: In patients with acute ischemic stroke, the standard of care is to perform intra-arterial endovascular thrombectomy in addition to intravenous thrombolysis. In this study, we investigated the different anesthetic techniques chosen for this procedure and clinical outcomes. Methods: Patients undergoing endovascular procedures were divided into three groups. The first group consisted of patients who received general anesthesia, the second group underwent the procedure under conscious sedation and local anesthesia at the catheter insertion site, and lastly the third group included patients who received only local anesthesia at the catheter insertion site, without sedation. Results: During the endovascular procedure, we did not notice significant differences in vital parameters, in particular the mean blood pressure (MAP) between patients treated with different types of anesthesia. Also, the duration of the revascularization did not show significant differences between the three groups. The main point is the absence of differences in terms of functional and clinical outcomes, using various scores as reference, such as the National Institutes of Health Stroke Scale (NIHSS) score at 7 days, NIHSS and Modified Rankin Scale (MRS) at time of discharge, and MRS after 3 months. These scores did not show significant differences in groups treated with different types of anesthesia. Conclusions: The rate of success of the revascularization procedure is almost overlapping between patients treated with conscious sedation and general anesthesia. In addition, we did not notice significant differences between groups in terms of functional and clinical outcomes. Considering the possible usefulness of applying conscious sedation, at OCSAE of Baggiovara, an internal protocol for conscious sedation was introduced to standardize the treatment in patients undergoing endovascular procedures.

Paired associative stimulation (PAS) is a non-invasive brain stimulation technique combining transcranial magnetic stimulation and peripheral nerve stimulation. PAS allows connections between cortical areas and peripheral nerves (C/P PAS) or between cortical regions (C/C PAS) to be strengthened or weakened by spike-timing-dependent neural plasticity mechanisms. Since PAS modulates both neurophysiological features and motor performance, there is growing interest in its application in neurorehabilitation. We aimed to synthesize evidence on the motor rehabilitation role of PAS in stroke patients. We performed a literature search following the PRISMA Extension for Scoping Reviews Framework. Eight studies were included: one investigated C/C PAS between the cerebellum and the affected primary motor area (M1), seven applied C/P PAS over the lesional, contralesional, or both M1. Seven studies evaluated the outcome on upper limb and one on lower limb motor recovery. Although several studies omit crucial methodological details, PAS highlighted effects mainly on corticospinal excitability, and, more rarely, an improvement in motor performance. However, most studies failed to prove a correlation between neurophysiological changes and motor improvement. Although current studies seem to suggest a role of PAS in post-stroke rehabilitation, their heterogeneity and limited number do not yet allow definitive conclusions to be drawn.

Shifts in the day of peak net primary production (NPP) were detected in different biogeochemical provinces of the North Atlantic (25–65° N). Most provinces displayed a shift toward earlier peak NPP, with the largest change points in the 21st century and in the northern parts of the domain. Furthermore, the occurrences of the first day with a mixed-layer depth (MLD) shallower than 40 m and the day of peak NPP are positively correlated over most of the domain. As was the case for the day of peak NPP, the largest change points for the day of MLD shallower than 40 m occur around or after the year 2000. Daily output from two fully coupled CMIP6 Earth system models, EC-Earth3-CC and NorESM2-LM, for the period 1750–2100 and under the SSP5-8.5 scenario, were used for the analysis. The ESM NPP data were compared with estimates derived from Carbon, Absorption and Fluorescence Euphotic-resolving (CAFE) satellite-based data. The ESMs showed significant differences from the CAFE model, though the timing of peak NPP was well captured for most provinces. The largest change points in the day of peak NPP occur earlier in EC-Earth3-CC than in NorESM2-LM. Although SSP5-8.5 is a scenario with very high warming, EC-Earth3-CC generates change points for most provinces in the early part of the 21st century, before the warming has deviated far from lower-emissions scenarios. NorESM2-LM displays the largest change points centered around the mid 21st century, with two out of eight provinces displaying the largest change point before the year 2050. The early timing of the detected shifts in some provinces in both ESMs suggests that similar shifts could already have been initiated or could start in the near future. This highlights the need for long-term monitoring campaigns in the North Atlantic.

Objective. Basic and translational research in pediatric cancer are essential to improve patient care. To critically assess the developments achieved in these areas in Latin America, we systematically reviewed information published between 2013 and 2023. Methods. Studies of basic and translational research performed by investigators in Latin America evaluating pediatric malignant solid and central nervous system tumors were retrieved from PubMed. Original articles published in English between 2013 and 2023 were included. Collaborations among Latin American authors or among Latin American authors working with researchers from other continents were also included. Studies were excluded if they focused only on adults or on basic research in tumor biology not specifically related to the tumor types analyzed in this review. Results. A total of 550 articles were retrieved, but after removal of duplicates, 514 articles were included in the analysis, the majority of which were authored by researchers affiliated with institutions in Argentina, Brazil and Mexico. These countries also had the highest number of collaborations on original articles published with authors from Europe and North America. Argentina had the highest number of collaborations on original publications, with coauthors from Brazil and Uruguay. The median impact factor of the 244 journals in which articles were published was 3.5. The most commonly studied tumors were osteosarcomas, neuroblastomas and medulloblastomas; the most commonly studied areas were molecular analysis, tumor cell biology and biomarkers. Conclusions. In Latin America, research in pediatric oncology is on the agenda, despite a notable disparity in publication rates and frequency of collaboration between countries. There is a need to strengthen scientific collaboration within Latin America and with countries from other continents to promote research and to develop novel treatment strategies that reflect the local needs of children in Latin America who have solid tumors and brain cancer.

ABSTRACT Objective: This study assessed the cost-effectiveness of radiofrequency ablation compared with percutaneous ethanol injection in patients with early hepatocellular carcinoma in relation to the objective response rate and costs related to the procedure. Methods: This was a prospective single-center randomized trial. The primary outcome was cost-effectiveness. Secondary outcomes were the complete response rate according to the modified response evaluation criteria in solid tumors 60 days after randomization and the complication rate within 180 60 days. Results: Fifty patients were placed into the following groups: percutaneous ethanol injection (n=23) and radiofrequency ablation (n=27). Fifty-four nodules were randomized (mean follow-up: 205.37 days). The estimated mean hospital cost was US$ 1854.11 and US$ 2770.96 for the Radiofrequency Ablation and Percutaneous Ethanol Injection Groups, respectively. The incremental cost-effectiveness ratio was US$ -2674.59, which is advantageous for radiofrequency ablation. After 60 d, 28 of 29 nodules in the Radiofrequency Ablation Group achieved complete response versus 12 of 22 in the Percutaneous Ethanol Injection Group (RD, 42.01 [95%CI= 20.55–63.24]; p0.05), respectively. Conclusion: Radiofrequency ablation was more cost-effective and achieved higher complete response and lower complication rates than the Percutaneous Ethanol Injection Group within this cohort. Registry of Clinical Trials: NCT06450613

Inflammation plays a pivotal role in the pathogenesis of primary and post-essential thrombocythemia or post-polycythemia vera myelofibrosis (MF) in close cooperation with the underlying molecular drivers. This inflammatory state is induced by a dynamic spectrum of inflammatory cytokines, although recent evidence points to the participation of additional soluble inflammatory mediators. Damage-associated molecular patterns (DAMPs) represent endogenous signals released upon cell death or damage which trigger a potent innate immune response. We assessed the contribution of two prototypical DAMPs, HMGB1 and S100A8/A9, to MF inflammation. Circulating HMGB1 and S100A8/A9 were elevated in MF patients in parallel to the degree of systemic inflammation and levels increased progressively during advanced disease stages. Patients with elevated DAMPs had higher frequency of adverse clinical features, such as anemia, and inferior survival, suggesting their contribution to disease progression. Monocytes, which are key players in MF inflammation, were identified as a source of S100A8/A9 but not HMGB1 release, while both DAMPs correlated with cell death parameters, such as serum LDH and cell-free DNA, indicating that passive release is an additional mechanism leading to increased DAMPs. HMGB1 and S100A8/A9 promote inflammation through binding to Toll-like receptor (TLR) 4, whereas the former also binds TLR2. Monocytes from MF patients were shown to be hyperactivated at baseline, as reflected by higher CD11b and tissue factor exposure and increased expression levels of proinflammatory cytokines IL-1β and IL-6. Patient monocytes showed preserved TLR4 and TLR2 expression and were able to mount normal or even exacerbated functional responses and cytokine upregulation following stimulation of TLR4 and TLR2. Elevated levels of endogenous TLR ligands HMGB1 and S100A8/A9 coupled to the finding of preserved or hyperreactive TLR-triggered responses indicate that DAMPs may promote monocyte activation and cytokine production in MF, fueling inflammation. Plasma IL-1β and IL-6 were elevated in MF and correlated with DAMPs levels, raising the possibility that DAMPs could contribute to cytokine generation in vivo. In conclusion, this study highlights that, in cooperation with classic proinflammatory cytokines, DAMPs represent additional inflammatory mediators that may participate in the generation of MF inflammatory state, potentially providing novel biomarkers of disease progression and new therapeutic targets.

ABSTRACT BACKGROUND: Colorectal cancer is the third most common type of cancer in Brazil, despite the availability of screening methods that reduce its risk. Colonoscopy is the only screening method that also allows therapeutic procedures. The proper screening through colonoscopy is linked to the quality of the exam, which can be evaluated according to quality criteria recommended by various institutions. Among the factors, the most used is the Adenoma Detection Rate, which should be at least 25% for general population. AIMS: To evaluate the quality of the screening colonoscopies performed in a quarternary private Brazilian hospital. METHODS: This is a retrospective study evaluating the quality indicators of colonoscopies performed at a private center since its inauguration. Only asymptomatic patients aged over 45 years who underwent screening colonoscopy were included. The primary outcome was the Adenoma Detection Rate, and secondary outcomes included polyps detection rate and safety profile. Subanalyses evaluated the correlation of endoscopic findings with gender and age and the evolution of detection rates over the years. RESULTS: A total of 2,144 patients were include with a mean age of 60.54 years-old. Polyps were diagnosed in 68.6% of the procedures. Adenoma detection rate was 46.8%, with an increasing rate over the years, mainly in males. A low rate of adverse events was reported in 0.23% of the cases, with no need for surgical intervention and no deaths. CONCLUSIONS: This study shows that high quality screening colonoscopy is possible when performed by experienced endoscopists and trained nurses, under an adequate infrastructure.