A nonradial bifurcation result with applications to supercritical problems

In this paper we consider the problem $-\Delta u=|x|^{\alpha} F(u)$ in $R^N$, with $\alpha>0$ and $N\ge3$. Under some assumptions on $F$ we deduce the existence of nonradial solutions which bifurcate from the radial one when $\alpha$ is an even integer.Comment: 20 page

Analysis of a Cardiac-Necrosis-Biomarker Release in Patients with Acute Myocardial Infarction via Nonlinear Mixed-Effects Models

The release of the cardiac troponin T (cTnT) in patients with acute myocardial infarc tion (AMI) has been analyzed through a methodology based on nonlinear mixed-effects (NME) models. The aim of this work concerns the investigation of any possible relationship between clin ical covariates and the dynamics of the release of cTnT to derive more detailed and useful clinical information for the correct treatment of these patients. An ad-hoc mechanistic model describing the biomarker release process after AMI has been devised, assessed, and exploited to evaluate the im pact of the available clinical covariates on the cTnT release dynamic. The following approach was tested on a preliminary dataset composed of a small number of potential clinical covariates: em ploying an unsupervised approach, and despite the limited sample size, dyslipidemia, a known risk factor for cardiovascular disease, was found to be a statistically significant covariate. By increasing the number of covariates considered in the model, and patient cohort, we envisage that this approach may provide an effective means to automatically classify AMI patients and to investigate the role of interactions between clinical covariates and cTnT relea

Effect of Individual and Selected Combined Treatments With Saline Solutions and Spent Engine Oil on the Processing Attributes and Functional Quality of Tomato (Solanum lycopersicon L.) Fruit: In Memory of Professor Leila Ben Jaballah Radhouane (1958-2021)

The results showed that soil electrical conductivity, (EC2: 7 dS/m) increased soluble solids, lycopene content, total phenolic content, hydrophilic and lipophilic radical scavenging activities (HRSA and LRSA) by 14.2, 149, 20, 46.4, and 19.0%, respectively, compared with control. Under 0.5% spent engine oil (SEO), flavonoid content decreased by 21.7% compared with the control. HRSA and LRSA of fruits subjected to EC2/SEO1 treatment were, respectively, 45.9 and 35.5% lower than control. The a*/b* ratio was positively and significantly (P < 0.01) correlated with beta-carotene (R = 0.78), lycopene (R = 0.68), total vitamin C (R = 0.71), alpha-tocopherol (R = 0.83), gamma-tocopherol (R = 0.66), HRSA (R = 0.93), LRSA (R = 0.80), and soluble solids (R = 0.84) suggesting that it may be a promising indicator of fruit quality in areas affected by such constraints. The research revealed that combined stresses induce responses markedly different from those of individual treatments, which strain the need to focus on how the interaction between stresses may affect the functional quality of tomato fruits

Analysis of the phytochemical composition of pomegranate fruit juices, peels and kernels: A comparative study on four cultivars grown in Southern Italy

The increasing popularity of pomegranate (Punica granatum L.), driven by the awareness of its nutraceutical properties and excellent environmental adaptability, is promoting a global expansion of its production area. This investigation reports the variability in the weight, moisture, pH, total soluble solids, carbohydrates, organic acids, phenolic compounds, fatty acids, antioxidant activities, and element composition of different fruit parts (juices, peels, and kernels) from four (Ako, Emek, Kamel, and Wonderful One) of the most widely cultivated Israeli pomegranate varieties in Salento (South Italy). To the best of our knowledge, this is the first systematic characterization of different fruit parts from pomegranate cultivars grown simultaneously in the same orchard and subjected to identical agronomic and environmental conditions. Significant genotype-dependent variability was observed for many of the investigated parameters, though without any correlation among fruit parts. The levels of phenols, flavonoids, anthocyanins, and ascorbic and dehydroascorbic acids of all samples were higher than the literature-reported data, as was the antioxidant activity. This is likely due to positive interactions among genotypes, the environment, and good agricultural practices. This study also confirms that pomegranate kernels and peels are, respectively, rich sources of punicic acid and phenols together, with several other bioactive molecules. However, the variability in their levels emphasizes the need for further research to better exploit their agro-industrial potential and thereby increase juice-production chain sustainability. This study will help to assist breeders and growers to respond to consumer and industrial preferences and encourage the development of biorefinery strategies for the utilization of pomegranate by-products as nutraceuticals or value-added ingredients for custom-tailored supplemented foods

Bortezomib Plus Dexamethasone Followed by Escalating Donor Lymphocyte Infusions for Patients with Multiple Myeloma Relapsing or Progressing after Allogeneic Stem Cell Transplantation

Abstract Multiple myeloma relapsing after allogeneic stem cell transplantation (alloSCT) has a poor outcome. To assess the safety and efficacy of bortezomib and dexamethasone (VD) combination followed by donor lymphocyte infusions (DLIs) in myeloma patients relapsing or progressing after alloSCT, a prospective phase II study was designed. The treatment plan consisted of three VD courses followed by escalated doses of DLIs in case of response or at least stable disease. Nineteen patients were enrolled with a median age of 57 years (range, 33 to 67); 14 patients were allografted from human leukocyte antigen–identical siblings and 5 from alternative donors. Sixteen of 19 patients received the planned treatment, but 3 patients did not: 2 patients because of disease progression and 1 refused. After the VD phase the response rate was 62%, with 1 complete remission, 6 very good partial remissions, 5 partial remissions, 2 patients with stable disease, and 5 with progressive disease. After the DLI phase, the response rate was 68%, but a significant upgrade of response was observed: 3 stringent complete remissions, 2 complete remissions, 5 very good partial remissions, 1 partial remission, 4 with stable disease, and 1 with progressive disease. With a median follow-up of 40 months (range, 29 to 68), the 3-year progression-free survival and overall survival rates were 31% and 73%, respectively. Neither unexpected organ toxicities, in particular severe neuropathy, nor severe acute graft-versus-host disease flares were observed. VD-DLIs is a safe treatment for multiple myeloma patients relapsing or progressing after alloSCT and may be effective

Impact of Cytomegalovirus Replication and Cytomegalovirus Serostatus on the Outcome of Patients with B Cell Lymphoma after Allogeneic Stem Cell Transplantation

n/

On the Dynamics of solitons in the nonlinear Schroedinger equation

We study the behavior of the soliton solutions of the equation i((\partial{\psi})/(\partialt))=-(1/(2m)){\Delta}{\psi}+(1/2)W_{{\epsilon}}'({\psi})+V(x){\psi} where W_{{\epsilon}}' is a suitable nonlinear term which is singular for {\epsilon}=0. We use the "strong" nonlinearity to obtain results on existence, shape, stability and dynamics of the soliton. The main result of this paper (Theorem 1) shows that for {\epsilon}\to0 the orbit of our soliton approaches the orbit of a classical particle in a potential V(x).Comment: 29 page

Antioxidants in Varieties of Chicory ( Cichorium intybus

We report the hydrophilic and lipophilic antioxidant activities, as well as the total phenol, flavonoid, tocochromanol (tocopherol and tocotrienol), and carotenoid contents in the edible portion of wild and cultivated varieties of chicory (Cichorium intybus L.) and in the basal rosette leaves of the wild species of poppy (Papaver rhoeas L.), known by natives as “paparina,” collected in the countryside of Salento (South Apulia, Italy). We analyzed (1) two cultivars of chicory, the “Catalogna” harvested in the area between S. Pietro Vernotico and Tuturano (Brindisi) and the “Otrantina” harvested in Otranto (Lecce); (2) two wild chicory ecotypes harvested in S. Pietro Vernotico (Brindisi) and Statte (Taranto), respectively; (3) the basal leaves of wild poppy harvested in Sternatia (Lecce). In all samples, our results showed that the hydrophilic antioxidant activity is, generally, higher than the lipophilic activity. Poppy leaves exhibited the highest hydrophilic and lipophilic antioxidant activities and the highest concentration of total phenols and flavonoids. Tocopherols were detected only as traces. Among the extracted carotenoids, lutein and β-carotene were the most abundant in all analyzed samples. Total carotenoid content was greater in wild than in cultivated plants

Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies

none20: Despite remarkable advances in the treatment of multiple myeloma in the last decades, the prognosis of patients harboring high-risk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors demonstrated to partially ameliorate the prognosis of high-risk patients. We pooled together data from two phase I/II trials on transplant-ineligible patients with multiple myeloma receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance. The aim of this analysis was to compare treatment outcomes in patients with standard- versus high-risk cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) analysis. High risk was defined by the presence of at least one chromosomal abnormality, including t(4;14), del17p and t(14;16). Overall, 94 patients were included in the analysis: 57 (61%) in the standard-risk and 37 (39%) in the high-risk group. Median follow-up was 38 months. In standard- vs. high-risk patients, we observed similar progression-free survival (3-year PFS: 52% vs. 43%, respectively; p=0.50), overall survival (3-year OS: 78% vs. 73%; p=0.38), and overall response rate (88% vs 95%; p=0.47), with no statistical differences between the two groups. No difference in terms of progression-free survival was observed between patients with or without del17p. Carfilzomib, used both as induction and maintenance agent for transplant-ineligible newly diagnosed multiple myeloma patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted into similar progression-free survival and overall survival, as compared to standard-risk patients. ClinicalTrials.gov IDs: NCT01857115 (IST-CAR-561) and NCT01346787 (IST-CAR-506).noneMina, Roberto; Bonello, Francesca; Petrucci, Maria Teresa; Liberati, Anna Marina; Conticello, Concetta; Ballanti, Stelvio; Musto, Pellegrino; Olivieri, Attilio; Benevolo, Giulia; Capra, Andrea; Gilestro, Milena; Galieni, Piero; Cavo, Michele; Siniscalchi, Agostina; Palumbo, Antonio; Montefusco, Vittorio; Gaidano, Gianluca; Omedé, Paola; Boccadoro, Mario; Bringhen, SaraMina, Roberto; Bonello, Francesca; Petrucci, Maria Teresa; Liberati, Anna Marina; Conticello, Concetta; Ballanti, Stelvio; Musto, Pellegrino; Olivieri, Attilio; Benevolo, Giulia; Capra, Andrea; Gilestro, Milena; Galieni, Piero; Cavo, Michele; Siniscalchi, Agostina; Palumbo, Antonio; Montefusco, Vittorio; Gaidano, Gianluca; Omedé, Paola; Boccadoro, Mario; Bringhen, Sar

Repurposing of tamoxifen ameliorates CLN3 and CLN7 disease phenotype

Batten diseases (BDs) are a group of lysosomal storage disorders characterized by seizure, visual loss, and cognitive and motor deterioration. We discovered increased levels of globotriaosylceramide (Gb3) in cellular and murine models of CLN3 and CLN7 diseases and used fluorescent-conjugated bacterial toxins to label Gb3 to develop a cell-based high content imaging (HCI) screening assay for the repurposing of FDA-approved compounds able to reduce this accumulation within BD cells. We found that tamoxifen reduced the lysosomal accumulation of Gb3 in CLN3 and CLN7 cell models, including neuronal progenitor cells (NPCs) from CLN7 patient-derived induced pluripotent stem cells (iPSC). Here, tamoxifen exerts its action through a mechanism that involves activation of the transcription factor EB (TFEB), a master gene of lysosomal function and autophagy. In vivo administration of tamoxifen to the CLN7Δex2 mouse model reduced the accumulation of Gb3 and SCMAS, decreased neuroinflammation, and improved motor coordination. These data strongly suggest that tamoxifen may be a suitable drug to treat some types of Batten disease.This work was funded by the European Union’s Horizon 2020 research and innovation programme (BATCure, grant No. 666918 to DLM, JPB, SEM, TB and SS). JPB is funded by the Agencia Estatal de Investigación (PID2019-105699RB-I00/ AEI / 10.13039/501100011033 and RED2018-102576-T), Plan Nacional sobre Drogas (2020I028), Junta de Castilla y León (Escalera de Excelencia CLU-2017-03), Ayudas Equipos Investigación Biomedicina 2017 Fundación BBVA and Fundación Ramón Areces. SS was funded by a grant from the Mila’s Miracle Foundation. TB was supported by German Research Council (DFG) grant FOR2625. SM benefits from MRC funding to the MRC Laboratory for Molecular Cell Biology University Unit at UCL (award code MC_U12266B) towards laboratory and office space. We acknowledge Marcella Cesana for providing the TFEB virus. Graphical abstract was created using BioRender.com