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Abstract Relapse remains a major cause of treatment failure following allogeneic stem cell transplantation (allo‐SCT) for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We retrospectively investigated low‐dose decitabine and venetoclax (DEC/VEN) as post‐transplant maintenance in 26 older patients with AML and MDS. The cumulative incidence of day 100 gIII‐IV acute graft versus host disease (GVHD) and 1‐year moderate‐severe chronic GVHD was 5% and 26%, respectively. One patient relapsed 14 m after transplant. The 1‐year non‐relapse mortality and survival were 11% and 84%, respectively. DEC/VEN is a safe and potentially effective strategy to reduce the risk of post‐transplant relapse.

Carbon nanofibers (CNFs) modified with CeO2 were employed as support for the synthesis of Ni catalysts for the CO2 methanation reaction. Two different preparation methods were investigated: incipient wetness impregnation and mechanochemical synthesis. The catalysts were tested at atmospheric pressure under a wide range of temperatures (200 – 600 °C) using a stoichiometric ratio of undiluted H2/CO2 and a flow to weight ratio of 600 NL h−1 gNi−1. The results showed that the Ni-CeO2/CNF catalyst prepared by mechanochemical synthesis showed higher CO2 conversion and CH4 selectivity at low temperatures than the one prepared via traditional method. This was attributed to smaller Ni crystallites and to the higher quantity of Ce3+ sites exposed by the milling process. Stress test carried out at 450 °C showed that the activity and the reaction mechanism remained stable for at least 50 h.

We investigated the effectiveness of an LED-based smart mid-block crosswalk system in mitigating the detrimental effects of driver engagement in non-driving-related tasks (NDRTs) with behavioural, performance, and subjective measurements. We designed a 2 (Crosswalk: smart vs conventional) by 2 (Task complexity: low vs. high NDRT) within-subjects experiment. Thirty-six drivers drove along four urban scenarios in a static driving simulator. We collected data on driving behaviour (speed, reaction distance), and safety (minimum time-to-collision [MTTC]), as well as subjective driver ratings on the perceived task load and their trust in the technology used, and performance levels achieved while performing the NDRTs.Behavioural and performance observations showed that the smart mid-block crosswalk resulted in greater reaction distances and MTTC values when drivers interacted with pedestrians, thus indicating improved safety. Remarkably, the results also revealed that increased NDRT complexity does not negatively affect the smart crosswalk effectiveness in terms of driver-pedestrian collision prevention (i.e., MTTC does not decrease significantly). However, the NDRT complexity influenced driving performance in terms of speed and reaction distance at brake pedal pressure, with drivers exhibiting lower speeds and lower reaction distances with higher task loads. Moreover, the subjective ratings and performance levels while performing a NDRT reflected the experimental manipulation, with drivers perceiving higher task loads and performing worse in the higher NDRT complexity condition. Overall, the smart mid-block crosswalk led to a safer driver-pedestrian interaction compared to conventional crosswalks and achieved a good acceptance level both of which augur well for the widespread future installation of this technology.

Sight obstructions along road curves can lead to a crash if the driver is not able to stop the vehicle in time. This is a particular issue along curves with limited available sight, where speed management is necessary to avoid unsafe situations (e.g., driving off the road or invading the other traffic lane). To solve this issue, we proposed a novel intelligent speed adaptation (ISA) system for visibility, called V-ISA (intelligent speed adaptation for visibility). It estimates the real-time safe speed limits based on the prevailing sight conditions. V-ISA comes with three variants with specific feedback modalities (1) visual and (2) auditory information, and (3) direct intervention to assume control over the vehicle speed.Here, we investigated the efficiency of each of the three V-ISA variants on driving speed choice and lateral behavioural response along road curves with limited and unsafe available sight distances, using a driving simulator. We also considered curve road geometry (curve direction: rightward vs. leftward). Sixty active drivers were recruited for the study. While half of them (experimental group) tested the three V-ISA variants (and a V-ISA off condition), the other half always drove with the V-ISA off (validation group). We used a linear mixed-effect model to evaluate the influence of V-ISA on driver behaviour.All V-ISA variants were efficient at reducing speeds at entrance points, with no discernible negative impact on driver lateral behaviour. On rightward curves, the V-ISA intervening variant appeared to be the most effective at adapting to sight limitations. Results of the current study implies that V-ISA might assist drivers to adjust their operating speed as per prevailing sight conditions and, consequently, establishes safer driving conditions.

This study explores the role of diversity in promoting learning innovation within educational courses teams. The focus is on the courses conducted under the ATTRACT Academy Umbrella; a co-innovation program funded by the European Commission's Horizon 2020 Program. The sample consists of three educational courses involving students from Esade Business School, Istituto Europeo di Design (IED), and Telecom and Computer Science Engineers students from UPC. The study adopts a case study approach, collecting qualitative and quantitative data from 88 students. Preliminary findings suggest that integration of diversity positively influences creative and innovative outcomes. The study aims to contribute to the research on how diversity impact learning innovation. The limitations include the correlational nature of the analysis and the need for further generalization.

Constipation is a disorder of the gastrointestinal (GI) and some of the main etiological mechanisms are directly related to changes in GI physiology. The capacity to carry out paired assessments and measure GI parameters under the influence of constipation is a relevant point in selecting a suitable methodology. We aimed to perform a non-invasive investigation of gastrointestinal motility in constipated rats using the alternating current biosusceptometry system (ACB). The animals were split into two groups: the pre-induction stage (CONTROL) and post-induction loperamide stage (LOP). We assessed GI motility parameters using the ACB system. Colon morphometric and immunohistochemical analyses were performed for biomarkers (C-kit) for interstitial cells of Cajal (ICC). Our results showed a significant increase in gastrointestinal transit in the LOP group in addition to a reduction in the dominant frequency of gastric contraction and an arrhythmic profile. A change in colonic contractility profiles was observed, indicating colonic dysmotility in the LOP group. We found a reduction in the number of biomarkers for intestinal cells of Cajal (ICC) in the LOP group. The ACB system can evaluate transit irregularities and their degrees of severity, while also supporting research into novel, safer, and more efficient treatments for constipation.

Abstract Cathelicidins, a family of host defence peptides in vertebrates, play an important role in the innate immune response, exhibiting antimicrobial activity against many bacteria, as well as viruses and fungi. This work describes the design and synthesis of shortened analogues of porcine cathelicidin PMAP-36, which contain structural changes to improve the pharmacokinetic properties. In particular, 20-mers based on PMAP-36 (residues 12-31) and 13-mers (residues 12-24) with modification of amino acid residues at critical positions and introduction of lipid moieties of different lengths were studied to identify the physical parameters, including hydrophobicity, charge, and helical structure, required to optimise their antibacterial activity. Extensive conformational analysis, performed by CD and NMR, revealed that the substitution of Pro25-Pro26 with Ala25-Lys26 increased the α-helix content of the 20-mer peptides, resulting in broad-spectrum antibacterial activity against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus epidermidis strains. Interestingly, shortening to just 13 residues resulted in only a slight decrease in antibacterial activity. Furthermore, two sequences, a 13-mer and a 20-mer, did not show cytotoxicity against HaCat cells up to 64 µM, indicating that both derivatives are not only effective but also selective antimicrobial peptides. In the short peptide, the introduction of the helicogenic α-aminoisobutyric acid forced the helix toward a prevailing 310 structure, allowing the antimicrobial activity to be maintained. Preliminary tests of resistance to Ser protease chymotrypsin indicated that this modification resulted in a peptide with an increased in vivo lifespan. Thus, some of the PMAP-36 derivatives studied in this work show a good balance between chain length, antibacterial activity, and selectivity, so they represent a good starting point for the development of even more effective and proteolysis-resistant active peptides.

Bacterial resistance represents a major health problem worldwide and there is an urgent need to develop first-in-class compounds directed against new therapeutic targets. We previously developed a drug-discovery platform to identify new antimicrobials able to disrupt the protein-protein interaction between the β' subunit and the σ70 initiation factor of bacterial RNA polymerase, which is essential for transcription. As a follow-up to such work, we have improved the discovery strategy to make it less time-consuming and more cost-effective. This involves three sequential assays, easily scalable to a high-throughput format, and a subsequent in-depth characterization only limited to hits that passed the three tests. This optimized workflow, applied to the screening of 5360 small molecules from three synthetic and natural compound libraries, led to the identification of six compounds interfering with the β'-σ70 interaction, and thus was capable of inhibiting promoter-specific RNA transcription and bacterial growth. Upon supplementation with a permeability adjuvant, the two most potent transcription-inhibiting compounds displayed a strong antibacterial activity against Escherichia coli with minimum inhibitory concentration (MIC) values among the lowest (0.87-1.56 μM) thus far reported for β'-σ PPI inhibitors. The newly identified hit compounds share structural feature similarities with those of a pharmacophore model previously developed from known inhibitors.

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of proline- and glutamine-rich proteins, widely termed “gluten”, in genetically susceptible individuals. CD induces an altered immune response that leads to chronic inflammation and duodenal mucosal damage. Currently, there are no specific tests for the accurate diagnosis of CD, and no drugs are available to treat this condition. The only available treatment strategy is lifelong adherence to a gluten-free diet. However, some studies have investigated the involvement of microRNAs (miRNAs) in CD pathogenesis. miRNAs are small noncoding ribonucleic acid molecules that regulate gene expression. Despite the growing number of studies on the role of miRNAs in autoimmune disorders, data on miRNAs and CD are scarce. Therefore, this study aimed to perform a literature review to summarize CD, miRNAs, and the potential interactions between miRNAs and CD in adults. This review shows that miRNA expression can suppress or stimulate pathways related to CD pathogenesis by regulating cell proliferation and differentiation, regulatory T-cell development, innate immune response, activation of the inflammatory cascade, focal adhesion, T-cell commitment, tissue transglutaminase synthesis, and cell cycle. Thus, identifying miRNAs and their related effects on CD could open new possibilities for diagnosis, prognosis, and follow-up of biomarkers.

Background: high-sensitive cardiac TroponinI (hs-cTnI) is widely used for diagnosis of acute coronary syndromes. The latest recommendation for hs-cTnI determination is the protocol 0–1 h finalized to improve the rule out accuracy of the test. A Point of Care Testing able to guarantee these performances could be very useful due to reducing the turnaround time and ruling out patients suspected of ACS, especially by using biological matrices that are not required for centrifuge. The aim of our work is to compare the results for hs-cTnI obtained using different biological matrices and anticoagulants, obtained between Atellica® VTLi hs-cTnI POCT and Access AccuTnI+3 DxI800 performances, in order to establish a possible bias derived directly from these pre-analytical conditions. Methods: Li-heparinized pool samples were primary employ for hs-cTnI with Atellica® VTLi as whole blood, then centrifuged and tested on Atellica® VTLi and DxI800. K3EDTA pool samples were centrifuged and measured on DxI800 too. A comparison of methods was performed according to CLSI_EP-09A2 protocol. Constant and proportional errors were investigated with Deming regression. Bias between methods was evaluated with the Bland Altman test. Results: comparing whole blood lithium heparin results obtained with Atellica versus lithium heparin and K3EDTA plasma tested on DxI 800, the Deming regression revealed a proportional error, whereas in both cases Bland Altman highlighted a minimal underestimation. A similar performance was revealed when considering plasma lithium heparin tested on Atellica versus lithium heparin and K3EDTA plasma obtained with DxI800, confirming the same underestimation. Considering values close to the cut off, no significant differences were found. Conclusions: in the laboratory, the estimation of the bias of two different analyzers is pivotal. Once more this is crucial when different biological matrices and anticoagulants are employed for the analysis. Our study demonstrates that no significant differences among the two matrices are present when comparing Atellica and DxI800 performances.

Introducción: A la fecha no existe consenso sobre la dosis óptima de verde de indocianina a administrar que permita el mayor realce de la vía biliar extrahepática con menor realce del parénquima hepático. El objetivo principal de este proyecto es analizar las diferencias entre una dosis de verde indocianina ajustada al peso de 0.0119mg/kg y una dosis de 2.5mg, una hora antes de la cirugía en pacientes operados de colecistectomía laparoscópica en el CMDLT en el tiempo comprendido entre abril – noviembre 2023. Métodos: ensayo clínico aleatorizado. Se evaluaron 30 pacientes y se dividieron en dos grupos según dosis administrada. Se obtuvieron datos generales y demográficos; del procedimiento quirúrgico se evaluó la intensidad de fluorescencia de la vía biliar. Luego de la cirugía se llenó la instrumento de recolección de datos, y se copiaron en una base de datos para ser analizado a posteriori. Resultados: No hubo reacciones adversas a la administración del fármaco, ni complicaciones trans o postoperatorias. Con la micro dosis el conducto cístico fue identificado en 42% y 82% antes y después de la disección del triángulo de Calot, mientras que con la dosis estándar un 30% y 93%, estas diferencias no fueron significativas, sin embargo, se aprecia una tendencia general de superioridad de la micro dosis. En pacientes con obesidad el porcentaje de identificación del conducto cístico con micro dosis y estándar fue de 0% y 33% p

The most common form of chronic liver disease, recently defined as MASLD, is strongly linked to obesity and metabolic syndrome. Lifestyle changes are part of MASLD prevention. The very low-calorie ketogenic diet (VLCKD) is a useful option for treating MASLD and reducing liver steatosis in patients with obesity. We assessed whether a greater degree of steatosis could have a positive or negative impact on how well 8 weeks of using the VLCKD improve steatosis and fibrosis in a patient population of overweight and obese individuals. Anthropometric parameters, along with changes in hormone and metabolic biomarkers, were also assessed both before and after the dietary change. The study population included 111 overweight (14.41%) or obese subjects (85.59%) aged between 18 and 64 years; the 75 women and 36 men involved were not taking any medicine. In both the raw (0.37 95% CI 0.21; 0.52) and the multivariate models (model a: 0.439 95% CI 0.26; 0.62; model b: 0.437 95% CI 0.25; 0.63), there was a positive and statistically significant correlation between the CAP delta value and the CAP before using the VLCKD. Additionally, the liver stiffness delta was found to be positively and statistically significantly correlated with liver stiffness before the use of the VLCKD in both models: the multivariate model (model a: 0.560 95% CI 0.40; 0.71; model b: 0.498 95% CI 0.34; 0.65) and the raw model (0.52 95% CI 0.39; 0.65). Systolic and diastolic blood pressure, insulin resistance (measured by HOMA-IR), insulin, HbA1c, fasting blood glucose, total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, BMI, waist circumference, and fat mass, were all decreased (p < 0.001) following the use of the VLCKD. However, following the use of the VLCKD, there was an increase in vitamin D levels. (p < 0.001). We found that using the VLCKD for 8 weeks has a greater effect on improving steatosis and fibrosis in subjects who initially have more severe forms of these conditions.

PURPOSERenal artery aneurysms (RAAs) are rare in the general population, although the true incidence and natural history remain elusive. Conventional endovascular therapies such as coil embolization or covered stent graft may cause sidebranches occlusion, leading to organ infarction. Flow-diverters (FD) have been firstly designed to treat cerebrovascular aneurysms, but their use may be useful to treat complex RAAs presenting sidebraches arising from aneurysmal sac. To evaluate mid-term follow-up (FUP) safety and efficacy of FD during treatment of complex RAAs.METHODSBetween November 2019 and April 2020, 7 RAAs were identified in 7 patients (4 men, 3 women; age range 55-82 years; median 67 years) and treated by FD. Procedural details, complications, morbidity and mortality, aneurysm occlusion and segmental artery patency were retrospectively reviewed. Twelve months computed tomography angiography (CTA) FUP was evaluated for all cases.RESULTDeployment of FD was successful in all cases. One intraprocedural technical complication was encountered with one FD felt down into aneurism sac which requiring additional telescopic stenting. One case at 3 months CTA FUP presented same complication, requiring same rescue technique. At 12 months CTA FUP 5 cases of size shrinkage and 2 cases of stable size were documented. No rescue surgery or major intraprocedural or mid-term FUP complication was seen.CONCLUSIONComplex RAAs with two or more sidebranches can be safely treated by FD. FD efficacy for RAA needs a further validation at long term FUP by additional large prospective studies.

Axl receptor tyrosine kinase and its ligand Gas6 regulate several biological processes and are involved in both the onset and progression of tumor malignancies and autoimmune diseases. Based on its key role in these settings, Axl is considered a promising target for the development of molecules with therapeutic and diagnostic purposes. In this paper, we describe the molecular characterization of the recombinant Ig1 domain of Axl (Ig1 Axl) and its biochemical properties. For the first time, an exhaustive spectroscopic characterization of the recombinant protein through circular dichroism and fluorescence studies is also reported, as well as a binding analysis to its natural ligand Gas6, paving the way for the use of recombinant Ig1 Axl as a bait in drug discovery screening procedures aimed at the identification of novel and specific binders targeting the Axl receptor.