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The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph-ALL) has significantly improved patients’ prognosis. Within the Campus ALL network we analyzed the outcome of adult Ph-ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial, to compare the real-life data with the study results. We included 421 consecutive patients, with a median age of 42 years. The complete remission (CR) rate after the first course of chemotherapy was 94% and a measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a multivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high risk (VHR) and MRD positive cases, transplanted (HSCT) patients had a significantly better DFS than non-HSCT ones (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large real-life cohort of Ph-ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial: CR rate after C1 94% vs 85%, P=0.0004; 3-year OS 67% vs 67%, P=0.94; 3-year DFS 57% vs 63%, P=0.17. HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.

Abstract Background Aligning delivery and financing systems across sectors to create broader systems of care can improve the health and well-being of families experiencing adversities. We aimed to identify structural and relational factors for best practices to achieve successful cross-sector collaboration among home visiting programs in the United States. Materials and methods We used a multiple case study approach to identify best practices for successful cross-sector collaboration between home visitors and other community service providers. We selected five diverse exemplary cases with cross-sector collaboration with variation in implementing agency type and geographic location. Cases were selected using a positive deviance approach based on strong coordination and integration with different community service provider types identified from previous survey data. We conducted in-depth qualitative interviews with home visiting staff, community providers, and clients with a total of 76 interviews conducted from 2021 to 2022. We wrote memos to synthesize themes within each case through data triangulation using interview data, documents, and site visit observations. We compared themes across the five cases to create a cross-case synthesis of best practices for successful cross-sector collaboration. Results Across the five cases, relational factors including leadership from all levels, champions across sectors, and shared goals between community providers were key factors for successful collaboration. Interpersonal relationships, coupled with the desire and capacity to engage, facilitated effective coordination to address families’ needs. At the structural level, shared data systems, written agreements, and co-location enabled care coordination activities. Community Advisory Boards provided a venue for developing partnerships, relationship-building, resource-sharing, and increasing awareness of home visiting. Conclusions We identified key elements of successful cross-sector collaboration across five case studies where home visitors coordinate care frequently and/or are structurally integrated with a range of providers. These learnings will inform future interventions to improve home visiting collaboration with other community providers to create a system of care to enhance family well-being.

Shallow landslides, frequently triggered by extreme events such as heavy rainfall, snowmelt, or earthquakes, affect vast areas with remarkable density. In the immediate aftermath of such events, it becomes crucial to rapidly assess landslides distribution and pinpoint the most severely affected areas to prioritize damage assessments and guide field survey operations effectively. Once the emergency phase subsides, the attention can shift to enhancing the accuracy of landslide inventory. In this work, we introduce the two-phase methodology “PANDA”, the unsuPervised shAllow laNdslide rapiD mApping, for the low-cost mapping of the potential landslides, firstly in the emergency phase and then, with an improved version, in the post-emergency one. This approach utilizes variations in NDVI derived from Sentinel-2 satellite imagery and geomorphological filters. We applied PANDA to rainfall events in the northeastern Apennine range, Italy, occurred in May 2023, causing dramatic social and economic consequences for this mountain territory. Within just five days of obtaining Sentinel-2 post-event imagery, we produced a reliable, ready-to-use map covering a vast area (∼4000 km2). The map tested during emergency field mapping shows positive feedback. In the post-emergency phase, accuracy was enhanced using completely cloud-free imagery, a filter to identify false positives associated with land use changes, a higher resolution digital terrain model (DTM), and an iterative approach to optimize NDVI and slope thresholds. Potential landslide density related with rainfall, indicating that the most severely affected region attained a density of approximately 50 landslides/km2. Validation against an independent manual inventory based on high-resolution imagery demonstrated encouraging accuracy results from both inventories, with a noticeable increase in the F1 score for the post-emergency version.

The global availability of Sentinel-2 data and the widespread coverage of cost-free and high-resolution images nowadays give opportunities to map, at a low cost, shallow landslides triggered by extreme events (e.g. rainfall, earthquakes). Rapid and low-cost shallow landslide mapping could improve damage estimations, susceptibility models and land management. This work presents a two-phase procedure to detect and map shallow landslides. The first is a semi-automatic methodology allowing for mapping potential shallow landslides (PLs) using Sentinel-2 images. The PL aims to detect the most affected areas and to focus on them an high-resolution mapping and further investigations. We create a GIS-based and user-friendly methodology to extract PL based on pre- and post-event normalised difference vegetation index (NDVI) variation and geomorphological filtering. In the second phase, the semi-automatic inventory was compared with a benchmark landslide inventory drawn on high-resolution images. We also used Google Earth Engine scripts to extract the NDVI time series and to make a multi-temporal analysis. We apply this procedure to two study areas in NW Italy, hit in 2016 and 2019 by extreme rainfall events. The results show that the semi-automatic mapping based on Sentinel-2 allows for detecting the majority of shallow landslides larger than satellite ground pixel (100 m2). PL density and distribution match well with the benchmark. However, the false positives (30 % to 50 % of cases) are challenging to filter, especially when they correspond to riverbank erosions or cultivated land.

Introduction: Exercise therapy may increase brain-derived neurotrophic factor (BDNF) levels and improve clinical outcomes in people living with Parkinson’s disease (PD). This systematic review was performed to investigate the effect of exercise therapy on BDNF levels and clinical outcomes in human PD and to discuss mechanisms proposed by authors. Method: A search on the literature was performed on PubMed up to December 2023 using the following key words: Parkinson’s disease AND exercise, exercise therapy, neurological rehabilitation AND brain-derived neurotrophic factor, brain-derived neurotrophic factor/blood, brain-derived neurotrophic factor/cerebrospinal fluid AND randomized clinical trial, intervention study. Only randomized clinical trials comparing an exercise intervention to treatment as usual, usual care (UC), sham intervention, or no intervention were included. Results: A meta-analysis of BDNF outcomes with pooled data from five trials (N = 216 participants) resulted in a significant standardized mean difference (SMD) of 1.20 [95% CI 0.53 to 1.87; Z = 3.52, p = 0.0004, I2 = 77%], favoring exercise using motorized treadmill, Speedflex machine, rowing machine, and non-specified exercise. Significant improvements were found in Unified Parkinson’s Disease Rating Scale (UPDRS), UPDRS-III, 6 Minute Walk Test (6MWT), and Berg Balance Scale (BBS). Methodological quality of trials was categorized as “good” in three trials, “fair” in one trial, and “poor” in one trial. Conclusion: Key results of this systematic review are that exercise therapy is effective in raising serum BDNF levels and seems effective in alleviating PD motor symptoms. Exercise therapy confers neuroplastic effects on Parkinson brain, mediated, in part, by BDNF.

Deep-seated gravitational slope deformations (DsGSDs) are slope-scale phenomena which are widespread in mountainous regions. Despite interacting with human infrastructures and settlements, only a few cases are monitored with ground-based systems. Remote sensing technologies have recently become a consolidated instrument for monitoring and studying such widespread and slow processes. This paper proposes a three-step novel methodology to analyze the morpho-structural domain of DsGSDs by exploiting the advanced Differential Synthetic Aperture Radar Interferometry (A-DInSAR) technique through (i) the analysis of A-DInSAR measurement point density and distribution defining a coverage threshold; (ii) the assessment of the actual ground deformation with respect to the orientation of phenomena based on slope, aspect, and C-index; and (iii) ground deformation mapping with previously ranked velocity interpolation. The methodology was tested on two differently oriented phenomena: the mainly north–south-oriented Croix de Fana and the mainly east–west-oriented Valtournenche DsGSD, located in the Aosta Valley Region, northern Italy. The results show a variation in the kinematic behavior between the morpho-structural domains, while also considering any other superimposed surficial deformations. This work provides the lines for the implementation of a rapid and low-cost tool based on the use of A-DInSAR measurements which are suitable for assessing the impact of any type of DsGSD on the anthropic facilities and infrastructures in mountainous areas.

Abstract The development of different generations of BCR-ABL1 tyrosine kinase inhibitors (TKIs) has led to the high overall survival of chronic myeloid leukemia (CML) patients. However, there are CML patients who show resistance to TKI therapy and are prone to progress to more advanced phases of the disease. So, implementing an alternative approach for targeting TKIs insensitive cells would be of the essence. Dihydroorotate dehydrogenase (DHODH) is an enzyme in the de novo pyrimidine biosynthesis pathway that is located in the inner membrane of mitochondria. Here, we found that CML cells are vulnerable to DHODH inhibition mediated by Meds433, a new and potent DHODH inhibitor recently developed by our group. Meds433 significantly activates the apoptotic pathway and leads to the reduction of amino acids and induction of huge metabolic stress in CML CD34+ cells. Altogether, our study shows that DHODH inhibition is a promising approach for targeting CML stem/progenitor cells and may help more patients discontinue the therapy.

Abstract Introduction Neurofibromatosis type 1 (NF1) is considered a model of neurodevelopmental disorder because of the high frequency of learning deficits, especially developmental coordination disorder. In neurodevelopmental disorder, Nicolson and Fawcett formulated the hypothesis of an impaired procedural learning system that has its origins in cortico-subcortical circuits. Our aim was to investigate the relationship between cortico-striatal connectivity and procedural perceptual-motor learning performance and motor skills in NF1 children. Methods Seventeen NF1 and 18 typically developing children aged between 8 and 12 years old participated in the study. All were right-handed and did not present intellectual or attention deficits. In all children, procedural perceptual-motor learning was assessed using a bimanual visuo-spatial serial reaction time task (SRTT) and motor skills using the Movement Assessment Battery for Children (M-ABC). All participants underwent a resting-state functional MRI session. We used a seed-based approach to explore cortico-striatal connectivity in somatomotor and frontoparietal networks. A comparison between the groups’ striato-cortical connectivity and correlations between connectivity and learning (SRTT) and motor skills (M-ABC) were performed. Results At the behavioral level, SRTT scores are not significantly different in NF1 children compared to controls. However, M-ABC scores are significantly impaired within 9 patients (scores below the 15th percentile). At the cerebral level, NF1 children present a higher connectivity in the cortico-striatal regions mapping onto the right angular gyrus compared to controls. We found that the higher the connectivity values between these regions, differentiating NF1 and controls, the lower the M-ABC scores in the whole sample. No correlation was found for the SRTT scores. Conclusion NF1 children present atypical hyperconnectivity in cortico-striatal connections. The relationship with motor skills could suggest a sensorimotor dysfunction already found in children with developmental coordination disorder. These abnormalities are not linked to procedural perceptual-motor learning assessed by SRTT.

Landslide inventories provide the knowledge basis for many geomorphological applications and also planning and emergency management. Detailed landslide inventories should also be prepared where pre-existing inventories are available, as knowledge updates. In this paper, we present a new geomorphological landslide inventory for an area of the High Agri Valley, Southern Italian Apennines. The map was prepared through systematic interpretation of historical aerial photographs testing extensive use of anaglyph glasses in StereoPhoto Maker freeware. A total of 2124 landslides were classified based on the type of movement, estimated depth, estimated relative age and three levels of uncertainty, providing landslide attributes and map constraints useful for land planning and hazard studies. The map also documents the relationships between landslides and fluvial landforms of different generations, recording important information to investigate the geomorphological evolution of the area further. We expect that landslide mapping in similar environments will benefit from the workflow here presented.

Rockfalls are a major hazard in mountain areas. They can endanger human settlements and infrastructures, and, every year, cause multiple damage and victims. An investigation of those areas more susceptible to rockfall represents a key approach to improve the analysis and management of rockfall impact and consequences. The proposed procedure involves the study of occurred rockfall databases and thematic maps to compute a susceptibility map, by the employment of Analytical Hierarchic Process. The computation is focused on the road network of Aosta Valley Region (northwestern Italy) and its proximity. The model results highlight the importance of morphometric factors on the investigated phenomena. The outcomes of the analysis were also validated by comparing rockfall databases with the receiver operating characteristic curve, in order to confirm their reliability. The results of the procedure are a starting point for a detailed planning action in order to manage the hazard related to these phenomena.

Sensorimotor adaptation involves the recalibration of the mapping between motor command and sensory feedback in response to movement errors. Although adaptation operates within individual movements on a trial-to-trial basis, it can also undergo learning when adaptive responses improve over the course of many trials. Brain oscillatory activities related to these “adaptation” and “learning” processes remain unclear. The main reason for this is that previous studies principally focused on the beta band, which confined the outcome message to trial-to-trial adaptation. To provide a wider understanding of adaptive learning, we decoded visuomotor tasks with constant, random or no perturbation from EEG recordings in different bandwidths and brain regions using a multiple kernel learning approach. These different experimental tasks were intended to separate trial-to-trial adaptation from the formation of the new visuomotor mapping across trials. We found changes in EEG power in the post-movement period during the course of the visuomotor-constant rotation task, in particular an increased (i) theta power in prefrontal region, (ii) beta power in supplementary motor area, and (iii) gamma power in motor regions. Classifying the visuomotor task with constant rotation versus those with random or no rotation, we were able to relate power changes in beta band mainly to trial-to-trial adaptation to error while changes in theta band would relate rather to the learning of the new mapping. Altogether, this suggested that there is a tight relationship between modulation of the synchronization of low (theta) and higher (essentially beta) frequency oscillations in prefrontal and sensorimotor regions, respectively, and adaptive learning.

Background:. Resident cosmetic clinics (RCCs) are the training modality of choice among both residents and faculty and are a mainstay at most residency programs.1–4 Despite this, knowledge of RCCs among plastic surgery consumers remains untested. We hypothesize that the public would be aware of and receptive to RCCs. Methods:. Participants with prior cosmetic procedures or interest in future cosmetic procedures were recruited using Amazon Mechanical Turk and asked to complete a survey in September 2020. First, prior awareness of RCCs was assessed. After a brief description of RCCs, perceptions of safety and preferences for care were assessed. Results:. After screening for quality, 815 responses were included. Forty-five percent of consumers were aware of RCCs. Seventy-six percent of consumers believed that RCCs were just as safe as attending clinics and 65% were comfortable receiving care from fourth-year residents or higher. Belief in RCC safety was associated with 4.8 times higher odds of feeling comfortable receiving care at an RCC [95% confidence interval (3.3–7.1), P < 0.001]. When given a hypothetical choice between residents and attendings in two scenarios, 46% of consumers chose residents for abdominoplasty and 60% chose residents for Botox injections. Belief in RCC safety was associated with choosing a resident or being indifferent in both scenarios. Conclusions:. Consumer preference regarding RCCs has largely been untested. This study shows that belief in RCC safety influences consumers’ perceived comfort with receiving care at an RCC. This knowledge can help guide RCC practice and maximize learning opportunities for surgeons-in-training.

The shallow landslides assessment is a hard task in territories featuring composite influence of natural and anthropic factors. In Liguria region (northwestern Italy), the landscape presents widespread human intervention prevalently represented by terraces. The assessment of predisposing factors in such landscape deserve a multidisciplinary approach. We implemented a classification methodology based on the Analytical Hierarchy Process. In GIS environment we overlaid several layers: (i) slope, (ii) land use, (iii) lithology, and (iv) aspect. Slope and aspect have been computed on a filtered (based on TPI) high-resolution DTM with the removal of terraces, in order to obtain the pristine slope pattern. Each spatial data was then reclassified according to the weighting procedures thus producing a landslide susceptibility map. This methodology represents a starting point for the correct assessment of shallow landslides occurrence, capable to generate a map, taking in account of the peculiar features of this extremely man-made territory.

En la actualidad, existen ciertas competencias genéricas que son consideradas tan importantes para el buen desempeño laboral como las competencias profesionales. Entre ellas se encuentran la capacidad de comunicación oral y escrita, de interactuar y trabajar en equipo, de crítica y autocrítica, de actuar en nuevas situaciones, de tomar decisiones, de motivar y conducir hacia metas comunes y de comprometerse con el medio socio-cultural. El presente estudio tuvo como objetivo conocer las competencias para la comunicación oral de los estudiantes de las asignaturas electivas de la carrera Medicina Veterinaria en la Universidad Nacional del Litoral. Se exploró acerca de estas competencias mediante una encuesta en línea administrada a dichos estudiantes. La misma fue diseñada en torno a distintas dimensiones relacionadas con las competencias para la comunicación oral: el propósito de la comunicación, el sentido bilateral o de intercambio del proceso comunicativo, la empatía del comunicador, el proceso de adaptación en la comunicación, la escucha activa, la combinación de habilidades de comunicación verbal y no verbal, y la comunicación oral estratégica en situaciones formales. Los resultados obtenidos revelaron que en términos generales los estudiantes perciben que las mismas son satisfactorias, aunque un número significativo manifestó tener ciertas dificultades en relación con la comunicación oral estratégica en situaciones formales. Esta investigación pone de manifiesto la importancia de realizar intervenciones didácticas afines al desarrollo y mejoramiento de competencias para la comunicación oral que contribuyan a cumplimentar con las exigencias de la futura actividad profesional de nuestros estudiantes.

Chronic myeloid leukemia stem cells (CML LSCs) are a rare and quiescent population that are resistant to tyrosine kinase inhibitors (TKI). When TKI therapy is discontinued in CML patients in deep, sustained and apparently stable molecular remission, these cells in approximately half of the cases restart to grow, resuming the leukemic process. The elimination of these TKI resistant leukemic stem cells is therefore an essential step in increasing the percentage of those patients who can reach a successful long-term treatment free remission (TFR). The understanding of the biology of the LSCs and the identification of the differences, phenotypic and/or metabolic, that could eventually allow them to be distinguished from the normal hematopoietic stem cells (HSCs) are therefore important steps in designing strategies to target LSCs in a rather selective way, sparing the normal counterparts.

In the autumn of 2014, a series of rainfall events affected several sectors of the Liguria region, triggering many shallow landslides and causing three casualties and severe structural damages. The most intensely unstable area covered 385 km2, in which more than 1600 landslides have been identified. After these events, an airborne Light Detection and Ranging survey was carried out. The survey yielded a high-resolution digital terrain model (DTM) and aerial images that provided a means of identifying and mapping all the occurred landslides. The distribution analysis of slope instabilities highlighted the link with various human activities. In fact, the majority of the detected landslides occurred in man-modified areas. Geospatial and statistical analyses provided the identification of three main anthropic factors: terraces, their level of maintenance and road network. Moreover, they quantified their role in landslide triggering. These factors were not analysed as separate elements, but as a continuous process, overlapping in time, in man-made influence on landscape. The identification of such factors is a key element for a correct behaviour characterization of this landscape towards extreme flash floods events.