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ImportanceDuring the SARS-CoV-2 pandemic, a complete physical isolation has been worldwide introduced. The impossibility of visiting their loved ones during the hospital stay causes additional distress for families: in addition to the worries about clinical recovery, they may feel exclusion and powerlessness, anxiety, depression, mistrust in the care team and post-traumatic stress disorder. The impossibility of conducting the daily meetings with families poses a challenge for healthcare professionals.ObjectiveThis paper aims to delineate and share consensus statements in order to enable healthcare team to provide by telephone or video calls an optimal level of communication with patient’s relatives under circumstances of complete isolation.Evidence reviewPubMed, Cochrane Database of Systematic Reviews, Database of Abstracts and Reviews of Effectiveness and the AHCPR Clinical Guidelines and Evidence Reports were explored from 1999 to 2019. Exclusion criteria were: poor or absent relevance regarding the aim of the consensus statements, studies prior to 1999, non-English language. Since the present pandemic context is completely new, unexpected and unexplored, there are not randomised controlled trials regarding clinical communication in a setting of complete isolation. Thus, a multiprofessional taskforce of physicians, nurses, psychologists and legal experts, together with some family members and former intensive care unit patients was established by four Italian national scientific societies. Using an e-Delphi methodology, general and specific questions were posed, relevant topics were argumented, until arriving to delineate position statements and practical checklist, which were set and evaluated through an evidence-based consensus procedure.FindingsTen statements and two practical checklists for phone or video calls were drafted and evaluated; they are related to who, when, why and how family members must be given clinical information under circumstances of complete isolation.Conclusions and relevanceThe statements and the checklists offer a structured methodology in order to ensure a good-quality communication between healthcare team and family members even in isolation, confirming that time dedicated to communication has to be intended as a time of care.

La valutazione dei pazienti con dolore toracico rappresenta una sfida quotidiana nonostante i molteplici progressi e le innovazioni avvenuti nelle due decadi trascorse. La percentuale dei pazienti che si presentano al Pronto Soccorso per un episodio di dolore toracico sono in costante aumento. I pazienti con sindrome coronarica acuta che sono dimessi dall’ospedale erroneamente presentano una prognosi avversa a breve termine. D’altronde, il ricovero di un paziente che si presenta con dolore toracico e risulta a basso rischio per un episodio di sindrome coronarica acuta causa una serie di procedure diagnostiche non necessarie con il loro relativo carico di complicazione ed aumento dei costi. A causa dell’impatto economico crescente sui sistemi sanitari che medici ed amministratori, pubblici e non, sono interessati al miglioramento dell’efficienza del processo di diagnosi e trattamento di questi pazienti. Dato che l’organizzazione dei diversi Pronto Soccorsi/Medina d’Urgenza (vedasi ad esempio la disponibilità di un’area di osservazione breve intensiva) e l’integrazione dei processi diagnostico-terapeutici tra medico dell’urgenza e cardiologo differiscono significativamente sul territorio nazionale, la finalità del presente position paper è duplice: primo, rivedere l’efficacia e l’utilità basata sull’evidenza dei vari mezzi diagnostici a disposizione e, secondo, delineare un percorso di base per la valutazione del dolore toracico (descrivendo i passaggi fondamentali per la cura e il trattamento del paziente) di facile implementazione al fine di standardizzare su tutto il territorio nazionale il percorso di diagnosi e cura del paziente con dolore toracico.

Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies are approved for the treatment of RAS wild-type (WT) metastatic colorectal cancer (mCRC), but the emergence of resistance mutations restricts their efficacy. We previously showed that RAS , BRAF and EGFR mutant alleles, which appear in circulating tumor DNA (ctDNA) during EGFR blockade, decline upon therapy withdrawal. We hypothesized that monitoring resistance mutations in blood could rationally guide subsequent therapy with anti-EGFR antibodies. We report here the results of CHRONOS, an open-label, single-arm phase 2 clinical trial exploiting blood-based identification of RAS / BRAF / EGFR mutations levels to tailor a chemotherapy-free anti-EGFR rechallenge with panitumumab (ClinicalTrials.gov: NCT03227926 ; EudraCT 2016-002597-12). The primary endpoint was objective response rate. Secondary endpoints were progression-free survival, overall survival, safety and tolerability of this strategy. In CHRONOS, patients with tissue- RAS WT tumors after a previous treatment with anti-EGFR-based regimens underwent an interventional ctDNA-based screening. Of 52 patients, 16 (31%) carried at least one mutation conferring resistance to anti-EGFR therapy and were excluded. The primary endpoint of the trial was met; and, of 27 enrolled patients, eight (30%) achieved partial response and 17 (63%) disease control, including two unconfirmed responses. These clinical results favorably compare with standard third-line treatments and show that interventional liquid biopsies can be effectively and safely exploited in a timely manner to guide anti-EGFR rechallenge therapy with panitumumab in patients with mCRC. Further larger and randomized trials are warranted to formally compare panitumumab rechallenge with standard-of-care therapies in this patient setting. In a phase 2 trial, monitoring tumor resistance mutations in blood using liquid biopsies allowed rationally guided subsequent therapy with anti-EGFR antibodies in patients with colorectal cancer.

Ceratitis capitata, is one of the most considerable invasive pests affecting fruit production worldwide. Conventional pesticides are generally formulated using organic solvents and emulsifiers that, in turn, are flammable and toxic. Thanks to their small size and biocompatibility, liposome-like formulations may significantly improve the efficacy and safety of conventional pesticides. This study aims to develop an alternative and innovative etofenprox formulation based on phospholipid vesicles (ethosomes) and evaluate its possible application for agricultural pest control. Ethosomes and geraniol-ethosomes were prepared by the one-step sonication method, achieving vesicles with small sizes (around 267 nm) and low polydispersity index (around 0.04). These vesicles were stable over 90 days of storage at room temperature and could slow the release of etofenprox (57 ± 4% released), in comparison with a commercial formulation (85 ± 5% released) after 24 h. Ethosomes and geraniol-ethosomes showed similar retention properties on lemon leaves (13.3 ± 1.0 to 14.4 ± 1.2 mg/cm 2 ) under laboratory condition. After open-field application, geraniol-ethosomes left the highest etofenprox residues on lemon leaves (14.3 ± 1.0 mg/kg), whereas the commercial formulation on the flavedo (4.1 ± 0.5 mg/kg). This result highlighted the possibility of reducing the application dose of etofenprox loaded in geraniol-ethosomes especially during the BBCH stage before fruiting. Both formulations displayed good biocompatibility with no significant cytotoxic effects on human keratinocytes (HaCat cells) across different etofenprox concentrations. Furthermore, laboratory bioassays revealed that geraniol-ethosomes exhibited a prolonged toxicity when sprayed against Ceratitis capitata adults, attributed to sustained release kinetics, underscoring their potential in environmentally sustainable agricultural pest management.

Population genetic studies provide accurate information on population structure, connectivity, and hybridization. These are key elements to identify units for conservation and define wildlife management strategies aimed to maintain and restore biodiversity. The Mediterranean island of Sardinia hosts one of the last autochthonous mouflon populations, descending from the wild Neolithic ancestor. The first mouflon arrived in Sardinia ~ 7000 years ago and thrived across the island until the twentieth century, when anthropogenic factors led to population fragmentation. We analysed the three main allopatric Sardinian mouflon sub-populations, namely: the native sub-populations of Montes Forest and Mount Tonneri, and the reintroduced sub-population of Mount Lerno. We investigated the spatial genetic structure of the Sardinian mouflon based on the parallel analysis of 14 highly polymorphic microsatellite loci and mitochondrial D-loop sequences. The Montes Forest sub-population was found to harbour the ancestral haplotype in the phylogeny of European mouflon. We detected high levels of relatedness in all the sub-populations and a mitochondrial signature of hybridization between the Mount Lerno sub-population and domestic sheep. Our findings provide useful insights to protect such an invaluable genetic heritage from the risk of genetic depletion by promoting controlled inter-population exchange and drawing informed repopulation plans sourcing from genetically pure mouflon stocks.

IntroductionIn patients with metastatic colorectal cancer (mCRC), baseline circulating tumour DNA (ctDNA) variant allele fraction (VAF) might serve as a surrogate of disease burden and should be evaluated in comparison with CEA and RECIST-defined sum of target lesions.MethodsIn this pre-planned analysis of the VALENTINO trial, we included patients with RAS wild-type mCRC receiving upfront FOLFOX/panitumumab with available baseline liquid biopsy. CtDNA was analysed by means of a 14-gene NGS panel. For each patient, the gene with the highest VAF in ctDNA was selected.ResultsThe final cohort included 135 patients. The median VAF was 12.6% (IQR: 2.0–45.2%). Higher VAF was observed in patients with liver metastases and with synchronous metastases presentation. Patients with high VAF had poorer median OS compared to those with low VAF (21.8 vs 36.5 months; HR: 1.82, 95%CI: 1.20–2.76; p = 0.005). VAF outperformed baseline CEA and target lesion diameter in the prognostic stratification and remained significantly correlated with OS (p = 0.003) in a multivariate model. VAF was not significantly correlated with dimensional response and PFS.ConclusionCtDNA measured by VAF is prognostic in patients with RAS wild-type mCRC. Response and PFS after an anti-EGFR-based first-line strategy are independent from initial tumour burden.

In this work, thioether-amide ligands featuring a combination of hard amide groups with soft donor groups have been employed to develop new zinc catalysts for the ring-opening polymerization of cyclic esters. All complexes were prepared in high yields through alkane elimination reactions with diethyl zinc and characterized using nuclear magnetic resonance (NMR) spectroscopy. Density functional theory (DFT) characterization provided insight into the parameters that influence catalytic activity, such as steric hindrance at the metal center, Lewis acidity and electronic density of thioether-amide ligands. In the presence of one equivalent of isopropanol, all complexes were active in the ring-opening polymerization of rac-β-butyrolactone. Quantitative conversion of 100 monomer equivalents was achieved within 1 h at 80 °C in a toluene solution. Number-average molecular weights increased linearly with monomer conversion; the values were in optimal agreement with those expected, and polydispersity index values were narrow and relatively constant throughout the course of polymerization. The most active complex was also effective in the ring-opening polymerization of ε-caprolactone and L-lactide. To propose a reliable reaction path, DFT calculations were undertaken. In the first step of the reaction, the acidic proton of the alcohol is transferred to the basic nitrogen atom of the amide ligand coordinated to the zinc ion. This leads to the alcoholysis of the Zn-N bond and the formation of an alcoholate derivative that starts the polymerization. In subsequent steps, the reaction follows the classical coordination–insertion mechanism.

This work proposes a systematic methodology for designing an active leveling system (ALS) actuator for lunar landing application. The ALS actuator is integrated into an inverted tripod leg layout, exploiting a honeycomb crushable damper as a shock absorber. The proposed ALS actuator is fitted within the leg’s primary strut and features a custom permanent-magnet synchronous machine rigidly coupled with a lead screw. The actuator aims to both provide proper leg deployment functioning and compensate for the different shock absorber deformations during landing. The leg dynamic behavior is simulated through a parameterized multi-body model to investigate different landing scenarios. First, a parametric sensitivity approach is used to optimize the transmission system and the electric machine characteristics. Then, the electric motor model is numerically validated and optimized through electromagnetic finite element analysis. To validate the proposed ALS design methodology, a virtual test bench is used to assess the ALS performances under different load scenarios. It is found that the proposed methodology is able to yield a compact, well-sized actuator which is numerically validated with the EL3 platform as a case study.

In the last few years, social media systems have experienced a fast growth. The amount of content shared in these systems increases fast, leading users to face the well known “interaction overload” problem, i.e., they are overwhelmed by content, so it becomes difficult to come across interesting items. To overcome this problem, social recommender systems have been recently designed and developed in order to filter content and recommend to users only interesting items. This type of filtering is usually affected by the “over-specialization” problem, which is related to recommendations that are too similar to the items already considered by the users. This paper proposes a friend recommender system that operates in the social bookmarking application domain and is based on behavioral data mining, i.e., on the exploitation of the users activity in a social bookmarking system. Experimental results show how this type of mining is able to produce accurate friend recommendations, allowing users to get to know bookmarked resources that are both novel and serendipitous. Using this approach, the impact of the “interaction overload” and the “over-specialization” problems is strongly reduced.