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Saint Louis’ failed crusade to Egypt has epitomized for centuries the high risks of conquering Egypt. Leibniz’s suggestion to the Sun King to conquer Egypt went unheeded. The key strategic value of Egypt for French interests reemerged in the course of the XVIII Century in several policy papers ignored by French diplomacy, which kept to the alliance with the Ottoman Empire. Only after the Revolution, the business interests of a merchant, the new colonial policy of a Foreign Minister and the ambition of a young General combined into launching the Egyptian expedition.

Abstract Acute promyelocytic leukemia (APL) is characterized by rearrangements of the retinoic acid receptor, RARα, which makes all-trans retinoic acid (ATRA) highly effective in the treatment of this disease, inducing promyelocytes differentiation. Current therapy, based on ATRA in combination with arsenic trioxide, with or without chemotherapy, provides high rates of event-free survival and overall survival. However, a decline in the drug activity, due to increased ATRA metabolism and RARα mutations, is often observed over long-term treatments. Furthermore, dedifferentiation can occur providing relapse of the disease. In this study we evaluated fenretinide, a semisynthetic ATRA derivative, encapsulated in nanomicelles (nano-fenretinide) as an alternative treatment to ATRA in APL. Nano-fenretinide was prepared by fenretinide encapsulation in a self-assembling phospholipid mixture. Physico-chemical characterization was carried out by dinamic light scattering and spectrophotometry. The biological activity was evaluated by MTT assay, flow cytometry and confocal laser-scanning fluorescence microscopy. Nano-fenretinide induced apoptosis in acute promyelocytic leukemia cells (HL60) by an early increase of reactive oxygen species and a mitochondrial potential decrease. The fenretinide concentration that induced 90–100% decrease in cell viability was about 2.0 µM at 24 h, a concentration easily achievable in vivo when nano-fenretinide is administered by oral or intravenous route, as demonstrated in previous studies. Nano-fenretinide was effective, albeit at slightly higher concentrations, also in doxorubicin-resistant HL60 cells, while a comparison with TK6 lymphoblasts indicated a lack of toxicity on normal cells. The results indicate that nano-fenretinide can be considered an alternative therapy to ATRA in acute promyelocytic leukemia when decreased efficacy, resistance or recurrence of disease emerge after protracted treatments with ATRA.

Abstract Wildfire smoke covers entire continents, depositing aerosols and reducing solar radiation fluxes to millions of freshwater ecosystems, yet little is known about impacts on lakes. Here, we quantified trends in the spatial extent of smoke cover in California, USA, and assessed responses of gross primary production and ecosystem respiration to smoke in 10 lakes spanning a gradient in water clarity and nutrient concentrations. From 2006 − 2022, the maximum extent of medium or high-density smoke occurring between June-October increased by 300,000 km2. In the three smokiest years (2018, 2020, 2021), lakes experienced 23 − 45 medium or high-density smoke days, characterized by 20% lower shortwave radiation fluxes and five-fold higher atmospheric fine particulate matter concentrations. Ecosystem respiration generally declined during smoke cover, especially in low-nutrient, cold lakes, whereas responses of primary production were more variable. Lake attributes and seasonal timing of wildfires will mediate the effects of smoke on lakes.

Objective: Colon adenocarcinoma is characterized by the downregulation of the retinoic acid receptor, making natural retinoids such as all-trans retinoic acid, 9-cis retinoic acid and 13-cis retinoic acid effective in treatment and chemoprevention due to their ability to increase RARβ expression. However, major limitations to their use include tolerability and acquired resistance. In this study, we evaluated fenretinide, a semisynthetic derivative of all-trans retinoic acid, in an HT-29 cell line. Fenretinide was evaluated both as a free drug and encapsulated in self-assembling phosphatidylcholine nanosystems with the aim of increasing the aqueous solubility and cell availability of the drug. Methods: Fenretinide was encapsulated in lipid nanosystems obtained in water by the dispersion of an amphiphilic mixture of phospholipids, glyceryl tributyrate and polysorbate 80. The physico-chemical characterization of the nanosystems was carried out by dynamic light scattering and spectrophotometry. The biological activity was evaluated by quantitative phase imaging microscopy, MTT assay, flow cytometry and confocal laser-scanning fluorescence microscopy. Results: Fenretinide in phosphatidylcholine nanosystems was more active than free fenretinide in inhibiting HT-29 cells’ proliferation, as indicated by quantitative phase imaging data. Indeed, encapsulated fenretinide increased duplication time, decreased dry mass and decreased the rate of cell growth more efficiently than fenretinide. Moreover, encapsulated fenretinide effectively decreased the motility of the cells that survived the treatment. Conclusions: The results indicate that the proposed nanosystems can be considered a valuable alternative to natural retinoids in the chemoprevention and treatment of colorectal cancer. This is due to the favorable pharmacologic characteristics of fenretinide in colorectal cancer and the improved drug activity provided by nanoencapsulation.

Purpose: This study investigated whether family-school conflict, directly and indirectly, predicts behavioral regulatory strategies (via emotion regulation) among women in higher education. The authors aim to hypothesize that the direct and indirect effects would vary by race/ethnicity. Design/methodology/approach: Participants were 1,872 incoming first-year female students from a large, racially/ethnically diverse urban public university. They were classified into four racial/ethnic groups: 22% Asian American (n = 403), 11% Black (n = 209), 46% Latina (n = 865), and 21% White (n = 395). Data were collected from institutional records and an online student pre-matriculation survey. Multigroup structural equation modeling (SEM) was performed to explore the structural relations among key variables. Findings: Family-school conflict was negatively associated with help-seeking in all racial/ethnic groups, whereas family-school conflict was negatively associated with time management only for Latina students. In addition, family-school conflict indirectly predicted time management and help-seeking through increased emotion regulation, particularly among Latina students. Originality/value: In considering racial heterogeneity, the results showed the importance of analyzing racial/ethnic groups separately to obtain more accurate information on self-regulation mechanisms in family-school conflict contexts.

Using multigroup structural equation modeling, this study examines whether family-work-school conflicts directly or indirectly predict transfer students' well-being (via self-regulation) across the periods of pre-, during, and post-COVID-19 lockdown in the Chicago metropolitan area in Illinois, United States. The results indicate that family-school conflict predicted well-being regardless of lockdown status, but work-school conflict predicted well-being only during the lockdown period. This study also discusses the importance of cognitive regulation for transfer students' transition in the middle of the pandemic.

Sage (Salvia officinalis L.) is a medicinal and aromatic plant (MAP) belonging to the Lamiaceae family. Its morphological, productive and chemical characteristics are affected by abiotic and biotic factors. The use of biostimulants seems to be one of the most interesting innovative practices due to fact they can represent a promising approach for achieving sustainable and organic agriculture. Despite a large application in horticulture, the use of biostimulants on MAPs has been poorly investigated. On this basis, a field experiment in a 2-year study was done to assess the effect of foliar treatments with different types of biostimulants (containing seaweeds, fulvic acids and protein hydrolysates) and two frequencies of application on morphological, productive, and chemical characteristics of S. officinalis grown organically in Mediterranean environment. Morphological, productive, and chemical parameters were affected by the factors. The biostimulant application generated higher plant height, chlorophyll content, relative water content, biomass yield and essential oil yield compared to control plants. In addition, more frequent application of biostimulants produced higher biomass and essential oil yield. The application of fulvic acid and protein hydrolysates every week produced the highest total fresh yields (between 3.9 and 8.7 t ha-1) and total dry yields (between 1.3 and 2.5 t ha-1). The essential oil yield almost doubled (33.9 kg ha-1) with a higher frequency of protein hydrolysates application. In this study, 44 essential oil compounds were identified, and the frequency factor significantly influenced the percentage of 38 compounds. The highest percentage of some of the most representative monoterpenes, such as 1,8-cineole, α-thujone and camphor, were observed in biostimulated plants, with average increases between 6% and 35% compared to control plants. The highest values for total phenolics, rosmarinic acid, antioxidant activity were obtained in control plants and with a lower frequency of biostimulant applications. This study emphasizes how biostimulant applications may be used to improve sage production performance and essential oil parameters when produced in agricultural organic system. At the same time, biostimulants application caused a decrease in total phenolic, antioxidant activity and rosmarinic acid values.

BackgroundSmell disorders are commonly reported with COVID-19 infection. The smell-related issues associated with COVID-19 may be prolonged, even after the respiratory symptoms are resolved. These smell dysfunctions can range from anosmia (complete loss of smell) or hyposmia (reduced sense of smell) to parosmia (smells perceived differently) or phantosmia (smells perceived without an odor source being present). Similar to the difficulty that people experience when talking about their smell experiences, patients find it difficult to express or label the symptoms they experience, thereby complicating diagnosis. The complexity of these symptoms can be an additional burden for patients and health care providers and thus needs further investigation. ObjectiveThis study aims to explore the smell disorder concerns of patients and to provide an overview for each specific smell disorder by using the longitudinal survey conducted in 2020 by the Global Consortium for Chemosensory Research, an international research group that has been created ad hoc for studying chemosensory dysfunctions. We aimed to extend the existing knowledge on smell disorders related to COVID-19 by analyzing a large data set of self-reported descriptive comments by using methods from natural language processing. MethodsWe included self-reported data on the description of changes in smell provided by 1560 participants at 2 timepoints (second survey completed between 23 and 291 days). Text data from participants who still had smell disorders at the second timepoint (long-haulers) were compared with the text data of those who did not (non–long-haulers). Specifically, 3 aims were pursued in this study. The first aim was to classify smell disorders based on the participants’ self-reports. The second aim was to classify the sentiment of each self-report by using a machine learning approach, and the third aim was to find particular food and nonfood keywords that were more salient among long-haulers than those among non–long-haulers. ResultsWe found that parosmia (odds ratio [OR] 1.78, 95% CI 1.35-2.37; P

This study examines whether self-efficacy predicted academic success (via self-regulation) for first-generation and continuing-generation college students (Model 1) and among various racial/ethnic groups (Model 2). The 3,316 ethnically diverse incoming freshmen from a large, urban, public university (53% first-generation) participated in this study (43% Latinx, 24% Asian American, 23% White, and 10% Black). Participants' ages ranged from 16 to 23 (M = 17.97, SD = 0.41). Prior to matriculation, participants completed the online institutional survey, including items exploring self-efficacy and self-regulation. This study distinguishes between emotional and behavioral aspects of self-regulation. To assess academic success outcomes, first-semester grade point averages and first-to-second year retention rates were collected from institutional data. Significant direct and indirect paths varied by generational status as well as race/ethnicity. Two types of self-regulation--emotional and behavioral regulation--had divergent effects. Increased behavioral regulation but decreased emotional regulation enhanced academic success. Findings highlight that differentiated interventions should be provided to meet diverse needs.

Among the works of Leibniz, those written as a young advisor to the Prince Elector of Mainz reveal unusual political sensitivity. However, his suggestion to the Sun King to conquer Egypt instead of attacking the Netherlands went unheeded, without leaving any trace in the French archives. Actually, the British rediscovered Leibniz’s plan and used it as a tool of information warfare against France. Later, during the 1840 Oriental Crisis, the Consilium Aegyptiacum resurfaced in France in an anti-British pamphlet. The Prussian General von Minutoli and the US Navy officer Alfred T. Mahan assessed Leibniz’s paper from different strategic perspectives.

Ponds are often identified by their small size and shallow depths, but the lack of a universal evidence-based definition hampers science and weakens legal protection. Here, we compile existing pond definitions, compare ecosystem metrics (e.g., metabolism, nutrient concentrations, and gas fluxes) among ponds, wetlands, and lakes, and propose an evidence-based pond definition. Compiled definitions often mentioned surface area and depth, but were largely qualitative and variable. Government legislation rarely defined ponds, despite commonly using the term. Ponds, as defined in published studies, varied in origin and hydroperiod and were often distinct from lakes and wetlands in water chemistry. We also compared how ecosystem metrics related to three variables often seen in waterbody definitions: waterbody size, maximum depth, and emergent vegetation cover. Most ecosystem metrics (e.g., water chemistry, gas fluxes, and metabolism) exhibited nonlinear relationships with these variables, with average threshold changes at 3.7 ± 1.8 ha (median: 1.5 ha) in surface area, 5.8 ± 2.5 m (median: 5.2 m) in depth, and 13.4 ± 6.3% (median: 8.2%) emergent vegetation cover. We use this evidence and prior definitions to define ponds as waterbodies that are small (

Rapeseed (Brassica napus var. oleifera D.C.) and Ethiopian mustard (Brassica carinata A. Braun) are promising industrial crops for cultivation in the Southern Mediterranean area due to profitable yields under semi-arid conditions. The exploitation of raw materials produced by these crops is very convenient for farmers to produce bioenergy directly on-farm and permits them to create a short agri-energy supply chain. The purpose of this study was to determine their yield performance under rainfed conditions and make an economic assessment of a combined heat and power plant (CHP) system operating on pure vegetable oil (PVO). Tests were conducted in Sicily (Italy) from 2012 to 2014. Seed and crop residue yields were detected. The analysis of seed, defatted seed meal and crop residue, and the chemical-physical aspects of PVO were carried out according to conventional protocols. A pilot CHP system was used for cogenerating electricity and heat. In general, rapeseed had the highest seed (2.27 t ha−1) and oil (1.11 t ha−1) yields. The average oil content ranged from 44.88 % (Ethiopian mustard) to 45.73 % dry matter (rapeseed). Ethiopian mustard performed better than rapeseed in terms of aboveground biomass yield (5.49 t ha−1), in both years. The two crops showed different fatty acid profiles of the oil mainly due to diverse content of erucic and oleic acids. The CHP system had an average consumption of 14.41 kg PVO h−1. These results confirm that the productivity of the species can be appreciable in the Southern Mediterranean area and indicate the use of raw materials of these crops as crucial to the development a sustainable short agri-energy supply chain.

In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19-; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: -82.5 ± 27.2 points; C19-: -59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.

This study examines the early departure pathways of first-time freshmen university students to better understand the intersection of financial and time-related constraints that affect first-generation and low-income Black and Latinx students. Data from 50 interviews with students who experienced an early departure from a four-year university suggest that students' financial barriers are heightened as they matriculate because they are unsuspecting of the hidden costs of college. In turn, the financial- and time-related barriers operate as a double disadvantage that consequently pushes students out of higher education. The student's financial commitments and responsibilities become unmanageable and this is exacerbated by precarious family contexts, processes, and haphazard timing associated with limited financial resources. This study contributes to current research by expanding sociological theory related to the factors that contribute to persistent educational attainment inequalities along ethnoracial and socioeconomic lines, as well as informing policies and practices across higher education.

High school students' academic preparation (e.g. high school GPA, ACT composite score, AP credits earned) predicts and helps explain their academic performance at college. However, the effects of noncognitive factors on college success is less clear. This study examined the effects of adding high school students' (N = 2279) self-efficacy, motivation, sense of belonging and academic goal engagement to academic preparation, on academic success in college using structural equation modeling. Two models were compared: the basic model which included only academic preparation and the enhanced model which included both academic preparation and noncognitive factors. Results indicated that the enhanced model that included noncognitive factors provided a stronger explanation for college students' success. Further, academic goal engagement was more closely associated with performance whereas belonging was more closely associated with retention. The results of the current study have important implications for college administrators and future research.

ABSTRACTBackground Immune thrombocytopenia (ITP) is the most common acquired bleeding disorder. In both children and adults, the primary goal of any therapeutic approach consists of cessation of bleeding and its prevention. Several options are currently available for first-line therapy in Europe, including corticosteroids and intravenous immunoglobulin (IVIg) infusion, which has a similar efficacy and safety profile in both the pediatric and adult populations. When second-line therapy is needed in the pediatric setting, current guidelines recommend eltrombopag as the drug of choice.Procedure The aim of this article is to summarize the available evidence and present real-life experience on eltrombopag as second-line therapy in pediatric patients with ITP, with a focus on dosing and response to therapy as well as its tapering and discontinuation.Results In our setting, eltrombopag is associated with good safety profile as well as promising efficacy; dose de-escalation was feasible in 94% of cases and often reached very low pro/kg dosage, with full discontinuation in 15% of cases. In daily practice, a standardized approach for discontinuation of eltrombopag in pediatric patients with ITP is still lacking. Herein, an easy-to-use scheme for tapering and discontinuation in candidate pediatric patients is proposed that proposes 25% dose reduction every four weeks.Conclusions In future management of pediatric ITP patients, it will be crucial to assess if thrombopoietin receptor agonists might be more effective in earlier phases of the disease and can modify the course of the disease.

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.

Introduction: Fanconi anemia (FA) is a genome instability condition that drives somatic mosaicism in up to 25% of all patients, a phenomenon now acknowledged as a good prognostic factor. Herein, we describe the case of P1, a FA proband carrying a splicing variant, molecularly compensated by a de novo insertion.Methods and Results: Targeted next-generation sequencing on P1’s peripheral blood DNA detected the known FANCA c.2778 + 83C > G intronic mutation and suggested the presence of a large deletion on the other allele, which was then assessed by MLPA and RT-PCR. To determine the c.2778 + 83C > G splicing effect, we performed a RT-PCR on P1’s lymphoblastoid cell line (LCL) and on the LCL of another patient (P2) carrying the same variant. Although we confirmed the expected alternative spliced form with a partial intronic retention in P2, we detected no aberrant products in P1’s sample. Sequencing of P1’s LCL DNA allowed identification of the de novo c.2778 + 86insT variant, predicted to compensate 2778 + 83C > G impact. Albeit not found in P1’s bone marrow (BM) DNA, c.2778 + 86insT was detected in a second P1’s LCL established afterward, suggesting its occurrence at a low level in vivo. Minigene assay recapitulated the c.2778 + 83C > G effect on splicing and the compensatory role of c.2778 + 86insT in re-establishing the physiological mechanism. Accordingly, P1’s LCL under mitomycin C selection preserved the FA pathway activity in terms of FANCD2 monoubiquitination and cell survival.Discussion: Our findings prove the role of c.2778 + 86insT as a second-site variant capable of rescuing c.2778 + 83C > G pathogenicity in vitro, which might contribute to a slow hematopoietic deterioration and a mild hematologic evolution.

Rosemary (Rosmarinus officinalis L.) is an evergreen and a xerophytic shrub that is frequently employed in culinary, decorative, and industrial applications. It shows significant variations in biomass and essential oil (EO) yield due to effects of biotic and abiotic factors. Biostimulants are widely used in agriculture, and in organic agricultural systems, they may contribute significantly to the stability and/or to the increase in crop yields, ensuring respect for the environment. The aim of this study was to assess the effect of different types of biostimulants on the yield performance of rosemary. Four commercial formulations of biostimulants based on Eklonia maxima, Ascophyllum nodosum, fulvic acids, and protein hydrolysates were used for the tests. Water was used as a control. Six applications were performed. At harvest, several morphological and productive parameters were determined. All parameters were affected by biostimulant application. The highest fresh and dry yields were obtained with the application of fulvic acids (13.1 t ha−1 of fresh biomass and 4.3 t ha−1 of dry biomass) and protein hydrolysates (13.6 t ha−1 of fresh biomass and 4.4 t ha−1 of dry biomass) with values 60% higher than that of the control. Regarding the EO content in the dry biomass, the highest value (1.72% v/w) was found in control plants, whilst the lowest (1.14%) was observed in plants treated with fulvic acids. In the case of the EO yield, the lowest value (46.5 kg ha−1) per unit area was found in the control. The application of Eklonia maxima and protein hydrolysates produced the highest EO yield values, 65 kg ha−1 and 66.5 kg ha−1, respectively. This study highlights the use of biostimulants to increase the yield performance of rosemary when grown in an organic agricultural system.

Neutropenia, as an isolated blood cell deficiency, is a feature of a wide spectrum of acquired or congenital, benign or premalignant disorders with a predisposition to develop myelodysplastic neoplasms/acute myeloid leukemia that may arise at any age. In recent years, advances in diagnostic methodologies, particularly in the field of genomics, have revealed novel genes and mechanisms responsible for etiology and disease evolution and opened new perspectives for tailored treatment. Despite the research and diagnostic advances in the field, real world evidence, arising from international neutropenia patient registries and scientific networks, has shown that the diagnosis and management of neutropenic patients is mostly based on the physicians’ experience and local practices. Therefore, experts participating in the European Network for the Innovative Diagnosis and Treatment of Chronic Neutropenias have collaborated under the auspices of the European Hematology Association to produce recommendations for the diagnosis and management of patients across the whole spectrum of chronic neutropenias. In the present article, we describe evidence- and consensus-based guidelines for the definition and classification, diagnosis, and follow-up of patients with chronic neutropenias including special entities such as pregnancy and the neonatal period. We particularly emphasize the importance of combining the clinical findings with classical and novel laboratory testing, and advanced germline and/or somatic mutational analyses, for the characterization, risk stratification, and monitoring of the entire spectrum of neutropenia patients. We believe that the wide clinical use of these practical recommendations will be particularly beneficial for patients, families, and treating physicians.

Abstract Ponds are often identified by their small size and shallow depths, but the lack of a universal evidence-based definition hampers science and weakens legal protection. Here, we compile existing pond definitions, compare ecosystem metrics (e.g., metabolism, nutrient concentrations, and gas fluxes) among ponds, wetlands, and lakes, and propose an evidence-based pond definition. Compiled definitions often mentioned surface area and depth, but were largely qualitative and variable. Government legislation rarely defined ponds, despite commonly using the term. Ponds, as defined in published studies, varied in origin and hydroperiod and were often distinct from lakes and wetlands in water chemistry. We also compared how ecosystem metrics related to three variables often seen in waterbody definitions: waterbody size, maximum depth, and emergent vegetation cover. Most ecosystem metrics (e.g., water chemistry, gas fluxes, and metabolism) exhibited nonlinear relationships with these variables, with average threshold changes at 3.7 ± 1.8 ha (median: 1.5 ha) in surface area, 5.8 ± 2.5 m (median: 5.2 m) in depth, and 13.4 ± 6.3% (median: 8.2%) emergent vegetation cover. We use this evidence and prior definitions to define ponds as waterbodies that are small (

Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder of lymphocyte homeostasis classically due to mutation of FAS, FASL, and CASP10 genes (ALPS-FAS/CASP10). Despite recent progress, about one-third of ALPS patients does not carry classical mutations and still remains gene orphan (ALPS-U, undetermined genetic defects). The aims of the present study were to compare the clinical and immunological features of ALPS-FAS/CASP10 versus those of ALPS-U affected subjects and to deepen the genetic characteristics of this latter group. Demographical, anamnestic, biochemical data were retrieved from medical record of 46 ALPS subjects. An enlarged panel of genes (next-generation sequencing) was applied to the ALPS-U group. ALPS-U subjects showed a more complex phenotype if compared to ALPS-FAS/CASP10 group, characterized by multiorgan involvement (P = 0.001) and positivity of autoimmune markers (P = 0.02). Multilineage cytopenia was present in both groups without differences with the exception of lymphocytopenia and autoimmune neutropenia that were more frequent in ALPS-U than in the ALPS-FAS/CASP10 group (P = 0.01 and P = 0.04). First- and second-line treatments were able to control the symptoms in 100% of the ALPS-FAS/CASP10 patients, while 63% of ALPS-U needed >2 lines of treatment and remission in some cases was obtained only after target therapy. In the ALPS-U group, we found in 14 of 28 (50%) patients 19 variants; of these, 4 of 19 (21%) were known as pathogenic and 8 of 19 (42%) as likely pathogenic. A characteristic flow cytometry panel including CD3CD4-CD8-+TCRαβ+, CD3+CD25+/CD3HLADR+, TCR αβ+ B220+, and CD19+CD27+ identified the ALPS-FAS/CASP10 group. ALPS-U seems to represent a distinct entity from ALPS-FAS/CASP10; this is relevant for management and tailored treatments whenever available.

Livestock farming systems are criticised for their environmental impacts, but they can also provide various ecosystem services to society, especially permanent grasslands. This study aimed to develop a method to assess impacts of permanent grasslands and their management on the supply of regulation and maintenance ecosystem services applicable at the field and/or farm level. To this end, an existing framework, the Ecological Focus Areas Calculator, was adapted to (i) consider attributes and location parameters of permanent grasslands and (ii) integrate impacts of permanent grassland management on the provision of ecosystem services, which yielded a score for each ecosystem service. The method developed was tested with two farms. Analysis of mapping results, which calculated a score for each ecosystem service for each permanent grassland field on each farm, highlighted the direct relation between the novel approach and the underlying ecological theory of impacts on ecosystem services. On each farm, management practices influenced ecological processes differently, which led to different changes in ecosystem service scores. Applying this novel approach directly with farmers can help them identify win–win situations and trade-offs and target their management, by identifying the fields where it may be more optimal to focus certain management practices to decrease the farm’s overall impacts based on trade-offs at the individual-field scale. The novel approach combined representation of the complexity of interactions between management practices and ecological processes with the ability to provide results that are easy to use and interpret. Future development could help increase the accuracy of estimated impacts of management practices on ecosystem services, such as by adding additional practices or considering their long-term effects on ecological processes. The novel approach could also be updated to assess impacts of other types of land use, such as arable land, or management practices. The final goal of such a tool is to support decision-making to optimise the ecosystem services supplied by farming systems, which has advantages for society and for farmers.

The common reed (Phragmites australis): a natural capital used as bedding for housed suckler cows Description of the subject. The INRAE Saint Laurent de la Prée research farm, located in marshland, is looking for alternatives to cereal straw for housing its suckler cows. Objectives. This study aimed to explore the use of common reed (Phragmites australis) as bedding for suckler cows, through examination of its practical and economic aspects. Method. Conducted for two successive years (2018-2019), this study consisted of comparing different types of bedding composed of either reed or cereal straw in a free stall for suckler cows. Measurements were taken on the water absorption capacity of the bedding, the cleanliness of the cows with equal frequency and quantity of bedding provided, the composition of the compost from this bedding, and finally, the cost price of the reed. Results. Straw has a higher water absorption capacity than reed. The average weight gains of straw were approximately +63 and +41% in years 1 and 2, respectively, compared to reed. However, cows housed on reed were generally found to be in a similar state of cleanliness as those housed on straw. Reed compost has a fertilizing value very close to that of straw compost. The cost of reed was 53 €·t-1 and 92 €·t-1 for years 1 and 2. The cost of harvesting reed is competitive compared to the purchase of straw (100 €·t-1 straw delivered), and it is all the more so as the reed bed is close to the farm. Conclusions. Reed used as bedding for the housing of suckler cows could be an alternative to straw in marshland farms, provided that reedbeds are managed according to their biology and the biodiversity they contain.

Abstract Background Primary breast lymphoma (PBL) is an extremely rare neoplasm in children; by definition, it manifests in the breast without evidence of lymphoma elsewhere, except ipsilateral axillary nodes. Case presentation We report a case of a 15-year-old girl diagnosed with diffuse large B-cell lymphoma (DLBCL) of the right breast: the patient received chemotherapy and rituximab, achieving complete remission. A literature review revealed other 11 cases of pediatric PBL; it mainly affects female adolescents and can involve right and left breast equally. Different histologic subtypes have been described, arising from both B-cell and T-cell. Therapeutic approaches were very different, from chemotherapy to local treatment with surgery and/or radiotherapy. Conclusions Our case is the first in which rituximab was administered, suggesting to be a promising therapy in B-cell PBL, as already demonstrated in pediatric B-cell lymphoma from other sites. Further investigations are needed to identify prognostic factors and establish the most effective treatment.

AbstractBackgroundInherited thrombocytopenias (ITs) are rare congenital bleeding disorders characterized by different clinical expression and variable prognosis. ITs are poorly known by clinicians and often misdiagnosed with most common forms of thrombocytopenia.Material and methods“CHildren with Inherited Platelet disorders Surveillance” study (CHIPS) is a retrospective – prospective observational cohort study conducted between January 2003 and January 2022 in 17 centers affiliated to the Italian Association of Pediatric Hematology and Oncology (AIEOP). The primary objective of this study was to collect clinical and laboratory data on Italian pediatric patients with inherited thrombocytopenias. Secondary objectives were to calculate prevalence of ITs in Italian pediatric population and to assess frequency and genotype–phenotype correlation of different types of mutations in our study cohort.ResultsA total of 139 children, with ITs (82 male - 57 female) were enrolled. ITs prevalence in Italy ranged from 0.7 per 100,000 children during 2010 to 2 per 100,000 children during 2022. The median time between the onset of thrombocytopenia and the diagnosis of ITs was 1 years (range 0 - 18 years). A family history of thrombocytopenia has been reported in 90 patients (65%). Among 139 children with ITs, in 73 (53%) children almost one defective gene has been identified. In 61 patients a pathogenic mutation has been identified. Among them, 2 patients also carry a variant of uncertain significance (VUS), and 4 others harbour 2 VUS variants. VUS variants were identified in further 8 patients (6%), 4 of which carry more than one variant VUS. Three patients (2%) had a likely pathogenic variant while in 1 patient (1%) a variant was identified that was initially given an uncertain significance but was later classified as benign. In addition, in 17 patients the genetic diagnosis is not available, but their family history and clinical/laboratory features strongly suggest the presence of a specific genetic cause. In 49 children (35%) no genetic defect were identified. In ninetyseven patients (70%), thrombocytopenia was not associated with other clinically apparent disorders. However, 42 children (30%) had one or more additional clinical alterations.ConclusionOur study provides a descriptive collection of ITs in the pediatric Italian population.

γ-terpinene, α-terpinene, p-cymene, and myrcene are monoterpenes found in many essential oils extracted from a variety of plants and spices. Myrcene also occurs naturally in plants such as hops, cannabis, lemongrass, and verbena and is used as a flavoring agent in food and beverage manufacturing. In this research, the biological efficacy of γ-terpinene, α-terpinene, p-cymene, and myrcene was studied in human cell lines (HeLa, SH-SY5Y, and HDFa). Cytotoxicity, cell proliferation, cell migration, and morphology assays were performed to obtain detailed information on the anticancer properties. Our results show that myrcene has potential biological activity, especially in HeLa cells. In this cell line, it leads to an arrest of proliferation, a decrease in motility and morphological changes with loss of sphericity and thickness, and DNA damage. In addition, the interaction of γ-terpinene, α-terpinene, p-terpinene, and myrcene with calf thymus DNA (ct-DNA) was studied by UV-visible spectrophotometry. DNA binding experiments show that only myrcene can interact with DNA with an apparent dissociation constant (Kd) of 29 × 10−6 M.

The vegetative propagation of hops, despite being a reliable method, is not very common due to the unavailability of the plant material. In this study, the technique of in vitro propagation was applied to the Cascade variety of Humulus lupulus L. The plant material was collected from a private field in Sicily; the explants were subjected to sterilization before in vitro culture. Single-node explants were placed in in vitro culture in nine different culture media for multiplication. Thidiazuron (TDZ), Benzyladenine (BAP) and meta-Topoline (mT) were tested for multiplication phase. For the rooting phase, five types of different culture media were evaluated. Binodal cuttings coming from the previous multiplication test were placed in the culture. The rooting media differ from each other in the concentration and ratio of two auxin hormones: Indolo-3-acetic acid (IAA) and Indole-3-butyric acid (IBA). In vitro rooted plants obtained from the rooting phase were transferred to ex vitro conditions in a microbox with agri-perlite and a solution containing Murashige and Skoog (MS) basal medium at half concentration. With a culture medium containing the highest TDZ doses (H6) and combination with cytokinin (H8 and H9), the highest shoot percentage was obtained. After 3 months of in vitro culture, the highest shoot percentage was observed in the culture medium with 2 mL L−1 of BAP. The highest rooting percentage, roots numbers and root length were found when the culture medium was supplemented with 1 mL L−1 of IAA. The usage of agri-perlite and MS at half concentration, without PGR, allowed us to obtain a 99.1% survival rate. This micropropagation protocol is useful for obtaining virus-free plants and for the development of the brewery industry.

Anaplastic large cell lymphoma (ALCL) is a histological subtype of non-Hodgkin lymphoma, largely characterized by anaplastic lymphoma kinase (ALK) positivity, resulting from the chromosomal translocation t(2;5). We report a pediatric case of ALK-positive ALCL with primary concomitant involvement of bone and central nervous system (CNS); thereafter, a literature review about pediatric primary bone and primary CNS ALCL was conducted. According to the analyzed data, our case is unique because it is characterized by the contemporary involvement of the spine and CNS. During and after chemotherapy, our patient was monitored by detecting minimal residual disease (MRD) through the analysis of fusion transcript nucleophosmin-ALK. MRD assessment, not only in bone marrow but also in peripheral blood, seems to be a very powerful tool for predicting the prognosis of pediatric ALCL patients, as already described in the literature. Moreover, as shown in our case, it could be used during the follow-up for early recognition of relapse.

Abstract Chemosensory impairments have been established as a specific indicator of COVID-19. They affect most patients and may persist long past the resolution of respiratory symptoms, representing an unprecedented medical challenge. Since the SARS-CoV-2 pandemic started, we now know much more about smell, taste, and chemesthesis loss associated with COVID-19. However, the temporal dynamics and characteristics of recovery are still unknown. Here, capitalizing on data from the Global Consortium for Chemosensory Research (GCCR) crowdsourced survey, we assessed chemosensory abilities after the resolution of respiratory symptoms in participants diagnosed with COVID-19 during the first wave of the pandemic in Italy. This analysis led to the identification of two patterns of chemosensory recovery, partial and substantial, which were found to be associated with differential age, degrees of chemosensory loss, and regional patterns. Uncovering the self-reported phenomenology of recovery from smell, taste, and chemesthetic disorders is the first, yet essential step, to provide healthcare professionals with the tools to take purposeful and targeted action to address chemosensory disorders and their severe discomfort.

Objective: The association between celiac disease (CD) and immune thrombocytopenia (ITP) is still uncertain. The aim of this study was to characterize the coexistence of these two diseases in Italian children. Materials and Methods: This is a retrospective multicenter study investigating the occurrence of CD in 28 children with ITP diagnosed from January 1, 2000, to December 31, 2019. Results: The first diagnosis was ITP in 57.1% and CD in 32.1% of patients. In 3 patients (10.7%), the two diagnoses were simultaneous. All the potential and silent cases of CD in our cohort were diagnosed in the groups of 'ITP first' and 'simultaneous diagnosis'. In all children ITP was mild, and in 2 out of 8 not recovered from ITP at the time of CD diagnosis a normalization of platelet counts (>100,000/μL) occurred 3 and 5 months after starting a gluten-free diet, respectively. Conclusion: We think that screening for CD should be considered in children with ITP regardless of the presence of gastrointestinal symptoms. Furthermore, some patients may recover from ITP after starting a gluten-free diet.

This study compared 120 Chinese immigrant parents and 127 non-Chinese parents from New Zealand preschools on their level of involvement in preschool-based activities, as well as key predictors of parental involvement. Results showed that Chinese immigrant parents had a lower level of involvement than non-Chinese parents across three forms of involvement including communication with teachers, volunteering to help at the preschool, and participation in the preschool's decision making. For the entire sample, parental role construction and parenting self-efficacy were predictors of all three forms of involvement, and perceived opportunity for involvement was predictor of communication with teachers. For the Chinese immigrant sample, perceived opportunity for involvement predicted communication with teachers and participation in the preschool's decision making, and educational qualification predicted communication with teachers. The findings highlight the role of parents' motivational beliefs in parental involvement, in particular, the importance of teacher invitations for parental involvement among Chinese immigrant parents.

Several studies have examined the prognostic performance of therapeutic groups (TG) and early responses to therapy on positron emission tomography/computed tomography (PET/CT) in children and adolescents with classical Hodgkin lymphoma (cHL); less research has been performed on molecular parameters at diagnosis. The aim of the present study was to devise a scoring system based on the TG criteria for predicting freedom from progression (FFP) in 133 patients: 63.2% males; 14 years median age (interquartile range (IQR) 11.9–15.1); with cHL (108 nodular sclerosis (NS) subtype) treated according to the AIEOP LH-2004 protocol; and median 5.55 (IQR 4.09–7.93) years of follow-up. CHL progressed or relapsed in 37 patients (27.8%), the median FFP was 0.89 years (IQR = 0.59–1.54), and 14 patients (10.5%) died. The FPR (final prognostic rank) model associates the biological HLA-G SNP 3027C/A (numerical point assigned (pt) = 1) and absolute neutrophil count (>8 × 109/L, pt = 2) as variables with the TG (TG3, pt = 3). Results of FPR score analyses for FFP suggested that FPR model (Kaplan–Meier curves, log-rank test for trends) was better than the TG model. At diagnosis, high-risk patients classified at FPR rank 4 and 5 identified 18/22 patients who relapse during the follow-up.

Metallodrugs represent a combination of multifunctionalities that are present concomitantly and can act differently on diverse biotargets. Their efficacy is often related to the lipophilic features exhibited both by long carbo-chains and the phosphine ligands. Three Ru(II) complexes containing hydroxy stearic acids (HSAs) were successfully synthesized in order to evaluate possible synergistic effects between the known antitumor activity of HSA bio-ligands and the metal center. HSAs were reacted with [Ru(H)2CO(PPh3)3] selectively affording O,O-carboxy bidentate complexes. The organometallic species were fully characterized spectroscopically using ESI-MS, IR, UV-Vis, and NMR techniques. The structure of the compound Ru-12-HSA was also determined using single crystal X-ray diffraction. The biological potency of ruthenium complexes (Ru-7-HSA, Ru-9-HSA, and Ru-12-HSA) was studied on human primary cell lines (HT29, HeLa, and IGROV1). To obtain detailed information about anticancer properties, tests for cytotoxicity, cell proliferation, and DNA damage were performed. The results demonstrate that the new ruthenium complexes, Ru-7-HSA and Ru-9-HSA, possess biological activity. Furthermore, we observed that the Ru-9-HSA complex shows increased antitumor activity on colon cancer cells, HT29.

Rising environmental awareness drives green consumers to purchase sustainable cosmetics based on natural bioactive compounds. The aim of this study was to deliver Rosa canina L. extract as a botanical ingredient in an anti-aging gel using an eco-friendly approach. Rosehip extract was first characterized in terms of its antioxidant activity through a DPPH assay and ROS reduction test and then encapsulated in ethosomal vesicles with different percentages of ethanol. All formulations were characterized in terms of size, polydispersity, zeta potential, and entrapment efficiency. Release and skin penetration/permeation data were obtained through in vitro studies, and cell viability was assessed using an MTT assay on WS1 fibroblasts. Finally, ethosomes were incorporated in hyaluronic gels (1% or 2% w/v) to facilitate skin application, and rheological properties were studied. Rosehip extract (1 mg/mL) revealed a high antioxidant activity and was successfully encapsulated in ethosomes containing 30% ethanol, having small sizes (225.4 ± 7.0 nm), low polydispersity (0.26 ± 0.02), and good entrapment efficiency (93.41 ± 5.30%). This formulation incorporated in a hyaluronic gel 1% w/v showed an optimal pH for skin application (5.6 ± 0.2), good spreadability, and stability over 60 days at 4 °C. Considering sustainable ingredients and eco-friendly manufacturing technology, the ethosomal gel of rosehip extract could be an innovative and green anti-aging skincare product.

Safflower (Carthamus tinctorius L.) is a promising oilseed crop for cultivation in central Southern Italy due to its high tolerance to drought and salinity stress and appreciable seed and oil yields. The genetic diversity of cultivars and climate factors can affect fatty acid composition and yield traits. This study aimed to assess the effects of genotype and climate conditions on the productive performance of eight high oleic safflower genotypes under rainfed conditions in Sicily (Italy). These genotypes were compared to the Montola 2000 cultivar, which was used as a reference. Tests were carried out during the growing seasons of 2014–2015 and 2015–2016. The experimental design was a randomized complete block design with three replications. Morphological and yield components were significantly affected by genotype while the year had a significant effect on plant height only. In general, CTI 17 produced the highest seed yield (1.40 t ha−1) and oil yield (0.58 t ha−1). The seed oil content was found on 40.2% of dry matter, on average. The “genotype” factor significantly affected oil content and fatty acid composition. Oleic acid content was on average 66.1% and did not vary greatly over the two growing seasons. The above- and belowground plant parts showed the highest carbon content and the lowest nitrogen content as a percentage of dry matter. The results indicate that, under rainfed conditions, yield parameters of high oleic safflower genotypes can be profitable in southern Italy though significantly dependent upon genotype.

Abstract Olfactory impairment after a traumatic impact to the head is associated with changes in olfactory cortex, including decreased gray matter density and decreased BOLD response to odors. Much less is known about the role of other cortical areas in olfactory impairment. We used fMRI in a sample of 63 participants, consisting of 25 with post-traumatic functional anosmia, 16 with post-traumatic hyposmia, and 22 healthy controls with normosmia to investigate whole brain response to odors. Similar neural responses were observed across the groups to odor versus odorless stimuli in the primary olfactory areas in piriform cortex, whereas response in the frontal operculum and anterior insula (fO/aI) increased with olfactory function (normosmia > hyposmia > functional anosmia). Unexpectedly, a negative association was observed between response and olfactory perceptual function in the mediodorsal thalamus (mdT), ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (pCC). Finally, connectivity within a network consisting of vmPFC, fO, and pCC could be used to successfully classify participants as having functional anosmia or normosmia. We conclude that, at the neural level, olfactory impairment due to head trauma is best characterized by heightened responses and differential connectivity in higher-order areas beyond olfactory cortex.

Functional connectivity approaches have long been used in cognitive neuroscience to establish pathways of communication between and among brain regions. However, the use of these analyses to better understand how the brain processes chemosensory information remains nascent. In this review, we conduct a literature search of all functional connectivity papers of olfaction, gustation, and chemesthesis, with 103 articles discovered in total. These publications largely use approaches of seed-based functional connectivity and psychophysiological interactions, as well as effective connectivity approaches such as Granger Causality, Dynamic Causal Modeling, and Structural Equation Modeling. Regardless of modality, studies largely focus on elucidating neural correlates of stimulus qualities such as identity, pleasantness, and intensity, with task-based paradigms most frequently implemented. We call for further “model free” or data-driven approaches in predictive modeling to craft brain-behavior relationships that are free from a priori hypotheses and not solely based on potentially irreproducible literature. Moreover, we note a relative dearth of resting-state literature, which could be used to better understand chemosensory networks with less influence from motion artifacts induced via gustatory or olfactory paradigms. Finally, we note a lack of genomics data, which could clarify individual and heritable differences in chemosensory perception.