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Abstract A new system based on binary Deep Learning (DL) convolutional neural networks has been developed to recognize specific retinal abnormality signs on Optical Coherence Tomography (OCT) images useful for clinical practice. Images from the local hospital database were retrospectively selected from 2017 to 2022. Images were labeled by two retinal specialists and included central fovea cross-section OCTs. Nine models were developed using the Visual Geometry Group 16 architecture to distinguish healthy versus abnormal retinas and to identify eight different retinal abnormality signs. A total of 21,500 OCT images were screened, and 10,770 central fovea cross-section OCTs were included in the study. The system achieved high accuracy in identifying healthy retinas and specific pathological signs, ranging from 93 to 99%. Accurately detecting abnormal retinal signs from OCT images is crucial for patient care. This study aimed to identify specific signs related to retinal pathologies, aiding ophthalmologists in diagnosis. The high-accuracy system identified healthy retinas and pathological signs, making it a useful diagnostic aid. Labelled OCT images remain a challenge, but our approach reduces dataset creation time and shows DL models’ potential to improve ocular pathology diagnosis and clinical decision-making.

Enrico Gallo,1 Carlo Diaferia,2 Elisabetta Rosa,2 Giovanni Smaldone,1 Giancarlo Morelli,2 Antonella Accardo2 1IRCCS SDN, Naples, 80143, Italy; 2Department of Pharmacy and Research Centre on Bioactive Peptides (CIRPeB), University of Naples “Federico II”, Naples, 80134, ItalyCorrespondence: Antonella AccardoDepartment of Pharmacy and Research Centre on Bioactive Peptides (CIRPeB), University of Naples “Federico II”, Via Mezzocannone 16, Naples, 80134, ItalyTel +39 0812532045Fax +39 0812536642Email antonella.accardo@unina.itIntroduction: The clinical use of the antitumoral drug doxorubicin (Dox) is reduced by its dose-limiting toxicity, related to cardiotoxic side effects and myelosuppression. In order to overcome these drawbacks, here we describe the synthesis, the structural characterization and the in vitro cytotoxicity assays of hydrogels (HGs) and nanogels (NGs) based on short peptide sequences loaded with Dox or with its liposomal formulation, Doxil.Methods: Fmoc-FF alone or in combination with (FY)3 or PEG8-(FY)3 peptides, at two different ratios (1/1 and 2/1 v/v), were used for HGs and NGs formulations. HGs were prepared according to the “solvent-switch” method, whereas NGs were obtained through HG submicronition by the top-down methodology in presence of TWEEN® 60 and SPAN® 60 as stabilizing agents. HGs gelation kinetics were assessed by Circular Dichroism (CD). Stability and size of NGs were studied using Dynamic Light Scattering (DLS) measurements. Cell viability of empty and filled Dox HGs and NGs was evaluated on MDA-MB-231 breast cancer cells. Moreover, cell internalization of the drug was evaluated using immunofluorescence assays.Results: Dox filled hydrogels exhibit a high drug loading content (DLC=0.440), without syneresis after 10 days. Gelation kinetics (20– 40 min) and the drug release (16– 28%) over time of HGs were found dependent on relative peptide composition. Dox filled NGs exhibit a DLC of 0.137 and a low drug release (20– 40%) after 72 h. Empty HGs and NGs show a high cell viability (> 95%), whereas Dox loaded ones significantly reduce cell viability after 24 h (49– 57%) and 72 h (7– 25%) of incubation, respectively. Immunofluorescence assays evidenced a different cell localization for Dox delivered through HGs and NGs with respect to the free drug.Discussion: A modulation of the Dox release can be obtained by changing the ratios of the peptide components. The different cellular localization of the drug loaded into HGs and NGs suggests an alternative internalization mechanism. The high DLC, the low drug release and preliminary in vitro results suggest a potential employment of peptide-based HGs and NGs as drug delivery tools.Keywords: hydrogels, nanogels, drug delivery, peptide materials, doxorubicin, in vitro assays

Data from the National Survey of Children's Health 2016-2019 was used to examine the co-occurrence of autism and ADHD and the impact on anxiety and depression among adolescents age 12-17. Rates of anxiety and depression were up to ten-fold the prevalence of adolescents not diagnosed with autism or ADHD. Over half of autistic females (57%) and nearly half of autistic males (49%) are also diagnosed with ADHD. Autistic females with ADHD had the highest co-occurrence of anxiety at 72% followed by autistic males with ADHD at 69%. The prevalence of depression was highest among autistic adolescents with ADHD yet was consistent across genders (male/female) at 38-39%. Adolescents diagnosed with autism and/or ADHD are at heightened risk for anxiety and depression.

Paola Ringhieri,1 Silvia Mannucci,2 Giamaica Conti,2 Elena Nicolato,2 Giulio Fracasso,3 Pasquina Marzola,4 Giancarlo Morelli,1 Antonella Accardo1 1Department of Pharmacy and Interuniversity Research Centre on Bioactive Peptides (CIRPeB), University of Naples “Federico II”, Napoli, 2Department of Neurological Biomedical and Movement Sciences, 3Section of Immunology, Department of Medicine, 4Department of Informatics, University of Verona, Verona, Italy Abstract: Mixed liposomes, obtained by coaggregation of 1,2-dioleoyl-sn-glycero-3-phosphocholine and of the synthetic monomer containing a gadolinium complex ([C18]2DTPA[Gd]) have been prepared. Liposomes externally decorated with KCCYSL (P6.1 peptide) sequence in its monomeric, dimeric, and tetrameric forms are studied as target-selective delivery systems toward cancer cells overexpressing human epidermal growth factor receptor-2 (HER-2) receptors. Derivatization of liposomal surface with targeting peptides is achieved using the postmodification method: the alkyne-peptide derivative Pra-KCCYSL reacts, through click chemistry procedures, with a synthetic surfactant modified with 1, 2, or 4 azido moieties previously inserted in liposome formulation. Preliminary in vitro data on MDA-MB-231 and BT-474 cells indicated that liposomes functionalized with P6.1 peptide in its tetrameric form had better binding to and uptake into BT-474 cells compared to liposomes decorated with monomeric or dimeric versions of the P6.1 peptide. BT-474 cells treated with liposomes functionalized with the tetrameric form of P6.1 showed high degree of liposome uptake, which was comparable with the uptake of anti-HER-2 antibodies such as Herceptin. Moreover, magnetic MRI experiments have demonstrated the potential of liposomes to act as MRI contrast agents. Keywords: anti-HER2 liposomes, target peptide, KCCYSL peptide, breast cancer, click chemistry, branched peptides

Decadal and multidecadal changes in the meridional overturning circulation may originate from either the subpolar North Atlantic or the Southern Hemisphere. New records of carbon and oxygen isotopes from an eastern Martinique Island (Lesser Antilles) coral reveal irregular, decadal, double-step events of low ∆14C and enhanced vertical mixing, high δ18O and high δ13C values starting in 1885. Comparison of the new and published ∆14C records indicates that the last event (1956-1969) coincides with a widespread, double-step ∆14C low of South Atlantic origin from 32°N to 18°S, associated with a major slowdown of the Caribbean Current transport between 1963 and 1969. This event and the past Martinique ∆14C lows are attributed to pulses of northward advection of low ∆14C Sub-Antarctic Mode Waters into the tropical Atlantic. They are coeval with changes of the tropical freshwater budget and likely driven by meridional overturning circulation changes since ~1880.

Antonella Accardo,1 Mariateresa Vitiello,2,3 Diego Tesauro,1 Marilena Galdiero,2 Emiliana Finamore,2 Francesca Martora,2 Rosalba Mansi,1 Paola Ringhieri,1 Giancarlo Morelli11Department of Pharmacy, Interuniversitary Centre for Research on Bioactive peptides, CIRPeB, University of Naples "Federico II", Institute of Biostructures and Bioimaging IBB-CNR, Naples, Italy; 2Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Naples, Italy; 3Department of Clinical Pathology and Transfusion Medicine, University Hospital “Ruggi d'Aragona”, Salerno, ItalyAbstract: The use of micelle aggregates formed from peptide amphiphiles (PAs) as potential synthetic self-adjuvant vaccines to treat Herpes simplex virus (HSV) infection are reported here. The PAs were based on epitopes gB409-505 and gD301-309, selected from HSV envelope glycoprotein B (gB) and glycoprotein D (gD), that had their N-terminus modified with hydrophobic moieties containing two C18 hydrocarbon chains. Pure and mixed micelles of gB and/or gD peptide epitopes were easily prepared after starting with the synthesis of corresponding PAs by solid phase methods. Structural characterization of the aggregates confirmed that they were sufficiently stable and compatible with in vivo use: critical micelle concentration values around 4.0 · 10-7 mol · Kg-1; hydrodynamic radii (RH) between 50–80 nm, and a zeta potential (ζ) around – 40 mV were found for all aggregates. The in vitro results indicate that both peptide epitopes and micelles, at 10 µM, triggered U937 and RAW 264.7 cells to release appreciable levels of cytokines. In particular, interleukin (IL)-23-, IL-6-, IL-8- or macrophage inflammatory protein (MIP)-2-, and tumor necrosis factor (TNF)-α-release increased considerably when cells were treated with the gB-micelles or gD-micelles compared with the production of the same cytokines when the stimulus was the single gB or gD peptide.Keywords: epitopes, self-adjuvant vaccine, HSV

Antonella Accardo,1 Luigi Aloj,2 Michela Aurilio,2 Giancarlo Morelli,1 Diego Tesauro11Centro interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), Department of Pharmacy and Istituto di Biostrutture e Bioimmagini - Consiglio Nazionale delle Ricerche (IBB CNR), University of Naples “Federico II”, 2Department of Nuclear Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”, Napoli, ItalyAbstract: Active targeting by means of drug encapsulated nanoparticles decorated with targeting bioactive moieties represents the next frontier in drug delivery; it reduces drug side effects and increases the therapeutic index. Peptides, based on their chemical and biological properties, could have a prevalent role to direct drug encapsulated nanoparticles, such as liposomes, micelles, or hard nanoparticles, toward the tumor tissues. A considerable number of molecular targets for peptides are either exclusively expressed or overexpressed on both cancer vasculature and cancer cells. They can be classified into three wide categories: integrins; growth factor receptors (GFRs); and G-protein coupled receptors (GPCRs). Therapeutic agents based on nanovectors decorated with peptides targeting membrane receptors belonging to the GPCR family overexpressed by cancer cells are reviewed in this article. The most studied targeting membrane receptors are considered: somatostatin receptors; cholecystokinin receptors; receptors associated with the Bombesin like peptides family; luteinizing hormone-releasing hormone receptors; and neurotensin receptors. Nanovectors of different sizes and shapes (micelles, liposomes, or hard nanoparticles) loaded with doxorubicin or other cytotoxic drugs and externally functionalized with natural or synthetic peptides are able to target the overexpressed receptors and are described based on their formulation and in vitro and in vivo behaviors.Keywords: receptors binding peptides, drug delivery, nanoparticles, supramolecular aggregates, active targeting

Antonella Accardo1,2*, Giuseppina Salsano3*, Anna Morisco4, Michela Aurilio4, Antonio Parisi5, Francesco Maione5, Carla Cicala5, Diego Tesauro1,2, Luigi Aloj4, Giuseppe De Rosa3, Giancarlo Morelli1,21CIRPeB, Department of Biological Sciences and IBB CNR, University of Naples “Federico II”, 2Invectors srl, 3Department of Pharmaceutical Chemistry, University of Naples “Federico II”, 4Department of Nuclear Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”, 5Department of Experimental Pharmacology, University of Naples “Federico II”, Napoli, Italy*These authors contributed equally to this workObjectives: Drug delivery systems consisting of liposomes displaying a cell surface receptor-targeting peptide are being developed to specifically deliver chemotherapeutic drugs to tumors overexpressing a target receptor. This study addresses novel liposome composition approaches to specifically target tissues overexpressing bombesin (BN) receptors.Methods: A new amphiphilic peptide derivative (MonY-BN) containing the BN(7–14) peptide, the DTPA (diethylenetriaminepentaacetate) chelating agent, a hydrophobic moiety with two C18 alkyl chains, and polyethylene glycol spacers, has been synthesized by solid-phase methods. Liposomes have been generated by co-aggregation of MonY-BN with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). The structural and biological properties of these new target-selective drug-delivery systems have been characterized.Results: Liposomes with a DSPC/MonY-BN (97/3 molar ratio) composition showed a diameter of 145.5 ± 31.5 nm and a polydispersity index of 0.20 ± 0.05. High doxorubicin (Dox) loading was obtained with the remote pH gradient method using citrate as the inner buffer. Specific binding to PC-3 cells of DSPC/MonY-BN liposomes was obtained (2.7% ± 0.3%, at 37°C), compared with peptide-free DSPC liposomes (1.4% ± 0.2% at 37°C). Incubation of cells with DSPC/MonY-BN/Dox showed significantly lower cell survival compared with DSPC/Dox-treated cells, in the presence of 100 ng/mL and 300 ng/mL drug amounts, in cytotoxicity experiments. Intravenous treatment of PC-3 xenograft-bearing mice with DSPC/MonY-BN/Dox at 10 mg/kg Dox dose produced higher tumour growth inhibition (60%) compared with nonspecific DSPC/Dox liposomes (36%) relative to control animals.Conclusion: The structural and loading properties of DSPC/MonY-BN liposomes along with the observed in-vitro and in-vivo activity are encouraging for further development of this approach for target-specific cancer chemotherapy.Keywords: bombesin peptide, doxorubicin delivery, gastrin-releasing peptide receptors, PC-3 cells, theranostic applications

Inclusive sports have emerged as a potential tool for building social inclusion within diverse populations. The Special Olympics Unified Sports programs are an example of inclusion initiatives specific to students with intellectual disability and sports that can be reevaluated with new understandings of inclusion. This systematic mixed studies review aimed to capture athlete Unified Sports experiences and identify what athletes reported about their participation. The systematic review identified nine original studies conducted by six unrelated research groups. Results across the studies are synthesized and suggestions for future research are presented. Athletes in all nine studies reviewed reported positive experiences with Unified Sports leading to increased social inclusion and/or self-concepts.

One of the goals of modern orcharding is to produce a high volume of fruits with uniform size, organoleptic parameters, and health characteristics. The aim of this work was to study various shoot types and their prevailing positions along the cane and to identify how shoot type can influence the quality of fruit from the Actinidia tree. The experiment was conducted over a two-year period in a commercial orchard of Actinidia chinensis, cv. Gold 3. The shoots along the cane were classified as follows: spur shoots (SPs), terminated shoots (TEs), non-terminated shoots (NTs), and cut non-terminated shoots (CNTs). The data were statistically processed using ANOVA and Principal Component Analysis (ACP). Four different categories of fruit were obtained from the four shoot types, and their various attributes were compared. The prevailing category (comprising 55% of the studied fruits) was TEs, which are characterised by a higher soluble solid content, sweetness, and excellent health characteristics, as well as the reduced hardness of their pulp, which would support the hypothesis that harvesting could be brought forward. The second most common category (comprising 19% of total fruit) with the lowest soluble solid content, but a high antioxidant capacity, was that which was detached from the CNTs, while 13% of the fruit was produced from NTs, which had the lowest health value but good sweetness perception. Finally, the category with the lowest fruit percentage over the total fruit harvested (10%) was SPs, which are characterised by their smaller size. It has yet to be determined what the performance of each category will be post-harvest; whether it is possible to assign the quality categories while harvesting the fruit or to differentiate the harvest time accordingly remains subject to debate.

Special education teacher collaboration with families is essential to supporting students with disabilities, yet such partnerships often fall short in practice, and teachers report they are not adequately prepared to work with families. In order to prepare competent teachers for working with families, a Family Collaboration Project was incorporated into a special education teacher education program course taken concurrently with clinical practice in the field. Teacher candidates were assigned to intervention and comparison groups, with and without implementing the project, and their learning outcomes were compared through a pre-post survey and written reflection. Results show that candidates who participated in the intervention group increased their understanding of teacher--parent collaboration and increased their learning of communication skills in comparison to candidates who did not complete the Family Collaboration Project. In addition, compared to those in the comparison group, candidates in the intervention group provided more positive comments on the project reflection regarding their experience working with families and on the impact of collaboration with families on special education student outcomes.