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Hematopoietic stem cell transplantation is still a curative treatment for many haematological cancers. Many factors, such as age, sex, ethnic background, smoking status, and body mass index, affect average reference values in different populations. This study aimed to establish a reference range for the absolute numbers and percentages of healthy individuals' hematopoietic stem cells and immune cells in the bone marrow. Seventy-one healthy donors (32 males and 39 females) were enrolled in the study. Following bone marrow harvesting, using flow cytometry, immunophenotyping was performed to determine the absolute number and percentage of CD34+ stem cells and various immune subsets. We found no statistically significant difference in the absolute count of HSCs or immune cell subsets in the bone marrow between males and females. Regarding age, the younger group had more significant CD34+ and immune cell subsets. Donors with healthier body weights tend to have richer bone marrow cellularity. Establishing a reference value for hematopoietic stem cells and immune cells in the bone marrow based on various influential factors is pivotal for defining bone marrow status and donor selection.

IntroductionCharcot–Marie–Tooth disease (CMT) is an inherited neuropathy that affects the sensory and motor nerves. It can be considered the most common neuromuscular disease, with a prevalence of 1/2500.MethodsConsidering the absence of a specific medical treatment and the benefits shown by physical activity in this population, a systematic review was completed using several search engines (Scopus, PubMed, and Web of Science) to analyze the use, effectiveness, and safety of a training program performed in telecoaching (TC). TC is a new training mode that uses mobile devices and digital technology to ensure remote access to training.ResultsOf the 382 studies identified, only 7 met the inclusion criteria. The effects of a TC training program included improvements in strength, cardiovascular ability, and functional abilities, as well as gait and fatigue. However, the quality of the studies was moderate, the size of the participants in each study was small, and the outcome measured was partial.DiscussionAlthough many studies have identified statistically significant changes following the administration of the TC training protocol, further studies are needed, with appropriate study power, better quality, and a higher sample size.

Peels of Washington Navel (WAS), Navelina (NAV), and Vaniglia Apireno (VAN) orange fruits from Ribera (Sicily, Italy) represent abundant by-products of the Italian agro-food sector. In this work, volatile (VE) and non-volatile (NVE) extracts were obtained from fresh peels using a microwave-assisted protocol, and were characterized for their content in secondary metabolites and bioactivity. VEs exerted antibacterial activity against different pathogens, and were toxic on Caco2 cells. Their main component was limonene (>85 %). NVEs inhibited tyrosinase, amylase, and glucosidase in vitro, and exerted significant antioxidant effects on THP-1 XBlue cells. They showed also anti-inflammatory properties, by decreasing NF-κB activity in LPS-stimulated cells. Putative molecular effectors were highlighted by multivariate correlation analysis. Overall, NVEs may represent novel sustainable nutraceutical ingredients with anti-inflammatory and metabolic properties, and can be obtained by using eco-sustainable approaches. Our results will encourage the reuse of by-products of the orange processing chain and will contribute to increase its circularity in the future.

BackgroundNeuroblastoma (NB) is characterized by both adrenergic (ADRN) and undifferentiated mesenchymal (MES) subsets. The ganglioside sialic acid-containing glycosphingolipid (GD2) is widely overexpressed on tumors of neuroectodermal origin promoting malignant phenotypes. MES cells are greatly enriched in post-therapy and relapsing tumors and are characterized by decreased expression of GD2. This event may cause failure of GD2-based immunotherapy. NK cells represent a key innate cell subset able to efficiently kill tumors. However, the tumor microenvironment (TME) that includes tumor cells and tumor-associated (TA) cells could inhibit their effector function.MethodsWe studied eight NB primary cultures that, in comparison with commercial cell lines, more faithfully reflect the tumor cell characteristics. We studied four primary NB-MES cell cultures and two pairs of MES/ADRN (691 and 717) primary cultures, derived from the same patient. In particular, in the six human NB primary cultures, we assessed their phenotype, the expression of GD2, and the enzymes that control its expression, as well as their interactions with NK cells, using flow cytometry, RT-qPCR, and cytotoxicity assays.ResultsWe identified mature (CD105+/CD133−) and undifferentiated (CD133+/CD105−) NB subsets that express high levels of the MES transcripts WWTR1 and SIX4. In addition, undifferentiated MES cells display a strong resistance to NK-mediated killing. On the contrary, mature NB-MES cells display an intermediate resistance to NK-mediated killing and exhibit some immunomodulatory capacities on NK cells but do not inhibit their cytolytic activity. Notably, independent from their undifferentiated or mature phenotype, NB-MES cells express GD2 that can be further upregulated in undifferentiated NB-MES cells upon co-culture with NK cells, leading to the generation of mature mesenchymal GD2bright neuroblasts. Concerning 691 and 717, they show high levels of GD2 and resistance to NK cell-mediated killing that can be overcome by the administration of dinutuximab beta, the anti-GD2 monoclonal antibody applied in the clinic.ConclusionsNB is a heterogeneous tumor representing a further hurdle in NB immunotherapy. However, different from what was reported with NB commercial cells and independent of their MES/ADRN phenotype, the expression of GD2 and its displayed sensitivity to anti-GD2 mAb ADCC indicated the possible effectiveness of anti-GD2 immunotherapy.

This article addresses the critical issue of violence against children, defined as a violation of their rights across interpersonal, community, societal, and global settings, encompassing both physical and psychological actions targeting them or their parents. Globally, WHO estimates that an unacceptably large number of children aged 2–17 years, experience physical, sexual, or emotional violence or neglect yearly. War stands out as a major contributor to the infringement of children's fundamental human rights. Those in conflict zones undergo traumatic experiences, including the loss of family members, disruptions to social networks, displacement, and the denial of basic needs. The severe deprivation of essential resources and opportunities, coupled with the stress of warfare, poses a grave threat to the emotional and cognitive development of children, increasing the risk of physical and mental illnesses, disabilities, social problems, and intergenerational consequences. The article aims to draw attention to this issue and advocates for the development of appropriate academic and post-academic educational courses and training programs. This will better equip pediatricians and healthcare professionals to effectively combat violence against children in any context.

BackgroundPrevious studies evaluating the accuracy of computed tomography (CT) in detecting caudal vena cava (CVC) invasion by adrenal tumors (AT) used a binary system and did not evaluate for other vessels.ObjectiveTest a 7-point scale CT grading system for accuracy in predicting vascular invasion and for repeatability among radiologists. Build a decision tree based on CT criteria to predict tumor type.MethodsRetrospective observational cross-sectional case study. Abdominal CT studies were analyzed by 3 radiologists using a 7-point CT grading scale for vascular invasion and by 1 radiologist for CT features of AT.AnimalsDogs with AT that underwent adrenalectomy and had pre- and postcontrast CT.ResultsNinety-one dogs; 45 adrenocortical carcinomas (50%), 36 pheochromocytomas (40%), 9 adrenocortical adenomas (10%) and 1 unknown tumor. Carcinoma and pheochromocytoma differed in pre- and postcontrast attenuation, contralateral adrenal size, tumor thrombus short- and long-axis, and tumor and thrombus mineralization. A decision tree was built based on these differences. Adenoma and malignant tumors differed in contour irregularity. Probability of vascular invasion was dependent on CT grading scale, and a large equivocal zone existed between 3 and 6 scores, lowering CT accuracy to detect vascular invasion. Radiologists' agreement for detecting abnormalities (evaluated by chance-corrected weighted kappa statistics) was excellent for CVC and good to moderate for other vessels. The quality of postcontrast CT study had a negative impact on radiologists' performance and agreement.Conclusions and clinical importanceFeatures of CT may help radiologists predict AT type and provide probabilistic information on vascular invasion.

As the field of K-12 data science education continues to take form, humanistic approaches to teaching and learning about data are needed. Data feminism is an approach that draws on feminist scholarship and action to humanize data and contend with the relationships between data and power. In this review paper, we draw on principles from data feminism to review 42 different educational research and design approaches that engage youth with data, many of which are educational technology intensive and bear on future data-intensive educational technology research and design projects. We describe how the projects engage students with examining power, challenging power, elevating emotion and lived experience, rethinking binaries and hierarchies, embracing pluralism, considering context, and making labour visible. In doing so, we articulate ways that current data education initiatives involve youth in thinking about issues of justice and inclusion. These projects may offer examples of varying complexity for future work to contend with and, ideally, extend in order to further realize data feminism in K-12 data science education.

Abstract Background Carotid web (CaW) and carotid free-floating thrombus (CFFT) are rare yet critical causes of ischemic stroke in young adults. Case presentation A 54-year-old woman presented with a fluctuating right sensory-motor faciobrachial syndrome. A brain MRI scan revealed multiple small recent asynchronous cortico-subcortical ischemic foci in the vascular territory of the left internal carotid artery. A CT angiography identified a CFFT in the left internal carotid artery arising from an underlying CaW. The patient was treated with excellent clinical outcomes with carotid artery stenting and dual antiplatelet therapy. Conclusions We provide a structured pathophysiological rationale connecting CaW and CFFT and highlight pivotal therapeutic implications. Further studies are needed to investigate this relationship and guide assessment and treatment.

In this article we quantify the long-term economic impacts of coastal flooding in Europe. In particular, how the direct coastal damages generate long-term economic losses that propagate and compound throughout the century. A set of probabilistic projections of inundation-related direct damages (to residential buildings, firms' physical assets and agriculture production) is used as an exogenous shock to a dynamic stochastic economic model. The article considers explicitly the uncertainty related to the economic agents' behaviour and other relevant macroeconomic assumptions, i.e., how would consumers finance the repairing of their homes, how long does it take for a firm to reconstruct, whether firms decide to build-back-better after the inundation and possibly compensate the losses with a productivity gain. Our findings indicate that the long-term impacts of coastal floods could be larger than the direct damages. Under a high emission scenario (RCP8.5) the EU27 plus UK could lose every year between 0.25% and 0.91% of output by 2100, twice as much as the direct damages. The welfare losses present a strong regional variation, with the South (Bulgaria, Greece, Italy, Malta, Portugal and Spain), and United Kingdom (UK) plus Ireland regions showing the highest damages and a significant part of the population that could suffer significant welfare losses by the end of the century.

Abstract The outbreak of Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, forced us to face a pandemic with unprecedented social, economic, and public health consequences. Several nations have launched campaigns to immunize millions of people using various vaccines to prevent infections. Meanwhile, therapeutic approaches and discoveries continuously arise; however, identifying infected patients that are going to experience the more severe outcomes of COVID-19 is still a major need, to focus therapeutic efforts, reducing hospitalization and mitigating drug adverse effects. Microbial communities colonizing the respiratory tract exert significant effects on host immune responses, influencing the susceptibility to infectious agents. Through 16S rDNAseq we characterized the upper airways’ microbiota of 192 subjects with nasopharyngeal swab positive for SARS-CoV-2. Patients were divided into groups based on the presence of symptoms, pneumonia severity, and need for oxygen therapy or intubation. Indeed, unlike most of the literature, our study focuses on identifying microbial signatures predictive of disease progression rather than on the probability of infection itself, for which a consensus is lacking. Diversity, differential abundance, and network analysis at different taxonomic levels were synergistically adopted, in a robust bioinformatic pipeline, highlighting novel possible taxa correlated with patients’ disease progression to intubation.

Background: The advantages of mechanical assistance during ventricular tachycardia (VT) ablation have not been clinically demonstrated. We propose and discuss a technique, set up by us, that makes use of minimally invasive extra-corporeal circulation (MiECC) type III associated with a venous reservoir system, which allows complete cardiac flow support and blood oxygenation as well as hemodynamic stability during long-lasting procedures. Methods: We present a retrospective case series of ten patients with valvular heart disease and unresponsive Ventricular Tachycardia (VT) who underwent VT ablation with MiECC support. The mean age of the patients was 72 ± 8 years and the left ventricular ejection fraction was 36 ± 12%. All patients underwent a clinical evaluation to identify the cause of VT unresponsiveness (e.g., ischemic heart disease). Results: A total of 140 min, the following parameters were evaluated and recorded for 140 min. Central venous pressure (CVP) was used to evaluate excess volume. During the first 5 min, the mean was 15 mmHg, with a pump flow of 1.5 L/min and a mean systemic arterial pressure of 100 mmHg while setting up the circulation support. Following drainage in a volumetric bag of 1 L of blood, CVP was reduced to a value of 5 mmHg with a flow rate of 5 L/min and a mean systemic arterial pressure of 65 mmHg. In the case of small and low-weight patients our “1 L protocol” can be modified. Conclusions: In this preliminary retrospective case series, the MiECC type III system may represent the ideal support system during VT ablation, and further studies are needed to support this preliminary report.

Abstract Background The main therapy for rectal cancer patients is neoadjuvant therapy (NT) followed by surgery. Immune biomarkers are emerging as potential predictors of the response to NT. We performed a meta‐analysis to estimate their predictive significance. Methods A systematic literature search of PubMed, Ovid MEDLINE and EMBASE databases was performed to identify eligible studies. Studies on patients with rectal cancer undergoing NT in which the predictive significance of at least one of the immunological markers of interest was assessed by immunohistochemistry (IHC) in pretreatment biopsies were included. Results Seventeen studies reporting sufficient data met the inclusion criteria for meta‐analysis. High levels of total CD3+, CD4+ and CD8+ tumor infiltrating lymphocytes (TILs), as well as stromal and intraepithelial CD8+ compartments, significantly predicted good pathological response to NT. Moreover, high levels of total (tumoral and immune cell expression) PD‐L1 resulted associated to a good pathological response. On the contrary, high levels of intraepithelial CD4+ TILs were correlated with poor pathological response. FoxP3+ TILs, tumoral PD‐L1 and CTLA‐4 were not correlated to the treatment response. Conclusion This meta‐analysis indicated that high‐density TILs might be predictive biomarkers of pathological response in patients that underwent NT for rectal cancer.

Abstract The term “metastatic cascade” defines a process whereby few tumor cells complete a sequence of steps to leave the primary tumor to reach one or more sites elsewhere in the body, usually through the bloodstream to develop one or several metastases. Due to the nature and plasticity of cancer, unfortunately no specific and functional anti-metastatic drugs are available. In this Commentary, we are highlighting how four essential factors are able to induce adhesion-to-suspension transition (herein referred to as AST) in human cancer cells and how this process may play a key role in tumor metastasis. We further underlined the potential role of hematopoietic transcriptional regulators in reprogramming anchorage dependency of cells, supporting the possible targeting of AST factors as promising therapeutic strategy to overcome metastasis in solid tumor cells.