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Medical residents constitute a vulnerable population susceptible to mental health disorders. In Italy, this was evident during the COVID-19 pandemic, when medical residents served on the front line and provided significant support to healthcare services. Therefore, the working group on “Public Mental Health” of the Medical Residents’ Council of the Italian Society of Hygiene, Preventive Medicine, and Public Health (S.It.I.) designed the “Residents’ mental health investigation, a dynamic longitudinal study in Italy” (ReMInDIt). This longitudinal study aims to assess the mental status of medical residents and to explore potential cause–effect relationships between risk/protective factors (identified among sociodemographic, residency program, and lifestyle characteristics) and mental health outcomes (anxiety and depressive symptoms). Data will be collected from a study population of 3615 residents enrolled in Italian residency programs in public health, occupational medicine, and forensic medicine through an online questionnaire that includes validated tools, requires 10 min for completion, and is disseminated by the residents’ Councils. It will be followed by a follow-up administration after 12 months. The ReMInDIt study will play a significant role in generating evidence crucial for enhancing mental health services and promoting protective factors for the mental well-being of this important segment of healthcare professionals.

The phenyl(piperidin-4-yl)methanone fragment (here referred to as the benzoylpiperidine fragment) is a privileged structure in the development of new drugs considering its presence in many bioactive small molecules with both therapeutic (such as anti-cancer, anti-psychotic, anti-thrombotic, anti-arrhythmic, anti-tubercular, anti-parasitic, anti-diabetic, and neuroprotective agents) and diagnostic properties. The benzoylpiperidine fragment is metabolically stable, and it is also considered a potential bioisostere of the piperazine ring, thus making it a feasible and reliable chemical frame to be exploited in drug design. Herein, we discuss the main therapeutic and diagnostic agents presenting the benzoylpiperidine motif in their structure, covering articles reported in the literature since 2000. A specific section is focused on the synthetic strategies adopted to obtain this versatile chemical portion.

Introduction. Iron deficiency is common in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Oral iron supplementation is recommended in these patients, but it is associated with a higher incidence of gastrointestinal adverse reactions. Liposomal iron therapy has been proposed as a new iron formulation, improving iron bioavailability with less side effects; however, few data are available in patients with NDD-CKD. Methods. We designed a single-arm pilot study to evaluate the efficacy of liposomal iron administered for six months in correcting iron deficiency (defined as serum ferritin < 100 ng/mL and/or transferrin saturation < 20%) in patients with NDD-CKD stages 1–5. The primary endpoints were the achievement of serum ferritin ≥ 100 ng/mL and transferrin saturation ≥ 20%. Secondary outcomes were hemoglobin (Hb) changes and the safety of liposomal iron. Results. The efficacy population included 34/38 patients, who completed at least one visit after baseline. Liposomal iron increased the achievement of transferrin saturation targets from 11.8% at baseline to 50.0% at month 6 (p = 0.002), while no significant correction of serum ferritin (p = 0.214) and Hb was found (p = 0.465). When patients were stratified by anemia (Hb < 12 g/dL in women and Hb < 13 g/dL in men), a significant improvement of transferrin saturation was observed only in anemic patients (from 13.3 ± 5.8% to 20.2 ± 8.1%, p = 0.012). Hb values slightly increased at month 6 only in anemic patients (+0.60 g/dL, 95%CI −0.27 to +1.48), but not in those without anemia (+0.08 g/dL, 95%CI −0.73 to +0.88). In patients taking at least one dose of liposomal iron (safety population, n = 38), the study drug was discontinued in eight patients due to death (n = 2), a switch to intravenous iron (n = 2), and the occurrence of side effects (n = 4). Conclusions. The use of liposomal iron in patients with NDD-CKD is associated with a partial correction of transferrin saturation, with no significant effect on iron storage and Hb levels.

Abstract Background Putative pathogenic effects mediated by human endogenous retroviruses (HERVs) in neurological and psychiatric disorders in humans have been extensively described. HERVs may alter the development of the brain by means of several mechanisms, including modulation of gene expression, alteration of DNA stability, and activation of immune system. We recently demonstrated that autistic children and their mothers share high expression levels of some HERVs and cytokines in peripheral blood mononuclear cells (PBMCs) ex vivo, suggesting a close mother–child association in Autism Spectrum Disorder (ASD). Results In the present study, PBMCs from autistic children and their parents were exposed to stimulating factors (Interleukin-2/Phytohaemagglutinin) or drugs, as Valproic acid and Efavirenz. The results show that HERVs and cytokines expression can be modulated in vitro by different stimuli in PBMCs from autistic children and their mothers, while no significant changes were found in PBMCs ASD fathers or in controls individuals. In particular, in vitro exposure to interleukin-2/Phytohaemagglutinin or valproic acid induces the expression of several HERVs and cytokines while Efavirenz inhibits them. Conclusion Herein we show that autistic children and their mothers share an intrinsic responsiveness to in vitro microenvironmental changes in expressing HERVs and pro-inflammatory cytokines. Remarkably, the antiretroviral drug Efavirenz restores the expression of specific HERV families to values similar to those of the controls, also reducing the expression of proinflammatory cytokines but keeping the regulatory ones high. Our findings open new perspectives to study the role of HERVs in the biological mechanisms underlying Autism.

Abstract Background Nephropathy in Diabetes type 2 (NID-2) study is an open-label cluster randomized clinical trial that demonstrated that multifactorial intensive treatment reduces Major Adverse Cardiac Events (MACEs) and overall mortality versus standard of care in type 2 diabetic subjects with albuminuria and no history of cardiovascular disease. Aim of the present post-hoc analysis of NID- 2 study is to evaluate whether the number of risk factors on target associates with patient outcomes. Methods Intervention phase lasted four years and subsequent follow up for survival lasted 10 years. To the aim of this post-hoc analysis, the whole population has been divided into 3 risk groups: 0–1 risk factor (absent/low); 2–3 risk factors (intermediate); 4 risk factors (high). Primary endpoint was a composite of fatal and non-fatal MACEs, the secondary endpoint was all-cause death at the end of the follow-up phase. Results Absent/low risk group included 166 patients (52.4%), intermediate risk group 128 (40.4%) and high-risk group 23 (7.3%). Cox model showed a significant higher risk of MACE and death in the high-risk group after adjustment for confounding variables, including treatment arm (HR 1.91, 95% CI 1.04–3.52, P = 0.038 and 1.96, 95%CI 1.02–3.8, P = 0,045, respectively, vs absent/low risk group). Conclusions This post-hoc analysis of the NID-2 trial indicates that the increase in the number of risk factors at target correlates with better cardiovascular-free survival in patients with type 2 diabetes at high CV risk. Clinical Trial Registration ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925

IntroductionThere is accumulating evidence that many pathological conditions affecting human balance are consequence of postural control (PC) failure or overstimulation such as in motion sickness. Our research shows the potential of using the response to a complex postural control task to assess patients with early-stage Parkinson's Disease (PD).MethodsWe developed a unique measurement model, where the PC task is triggered by a moving platform in a virtual reality environment while simultaneously recording EEG, EMG and CoP signals. This novel paradigm of assessment is called BioVRSea. We studied the interplay between biosignals and their differences in healthy subjects and with early-stage PD.ResultsDespite the limited number of subjects (29 healthy and nine PD) the results of our work show significant differences in several biosignals features, demonstrating that the combined output of posturography, muscle activation and cortical response is capable of distinguishing healthy from pathological.DiscussionThe differences measured following the end of the platform movement are remarkable, as the induced sway is different between the two groups and triggers statistically relevant cortical activities in α and θ bands. This is a first important step to develop a multi-metric signature able to quantify PC and distinguish healthy from pathological response.

Cervical cancer (CC) is one of the most frequent cancers in women worldwide. The epithelial-mesenchymal transition (EMT) and the extracellular release of TGF-β are phenomena typically associated with different tumorigenic processes, including tumour cell proliferation and metastatization. Specific human microRNAs (miRNAs; miRs) involved in these tumorigenic processes have been identified, becoming important diagnostic and prognostic markers, and even potential therapeutic targets. In parallel, different studies have also shown that plant miRNAs can mediate a cross-kingdom regulation (CKR) of mammalian genes and modulate host's gene expression under pathological conditions, restoring the regulatory activity of endogenous miRNAs lost in cancer. In our previous studies, the miRNome from Moringa oleifera Lam. (henceforth moringa or mol) has been sequenced, showing the presence of several conserved miRNAs in the plant kingdom, whose ability to differentially regulate proliferation and apoptosis in healthy and cancer cells has been demonstrated. Furthermore, the effects of mol-miR treatment on tumorigenesis and EMT have been proved in liver tumour cells. According to these premises, we here investigated the proteomic profile of CC-derived HeLa cells exposed to a mol-miRNA pool, demonstrating the down-representation of specific factors involved in tumorigenesis. The treatment with plant miRs was able to modulate proteins involved in several biological processes linked to EMT. Furthermore, it reduced the expression of TGF-β and significantly inhibited cell motility, as observed following Scratch test and cell viability measurements, with a significant increase of apoptotic events. In conclusion, our results suggest and pave the way for the development of new potential therapeutic approaches based on CKR mediated by plant miRNAs for contrasting human cervical cancer, even in the form of adjuvants to classic treatments for limiting their side effects.

In February 2019, following the annual taxon ratification vote, the order Bunyavirales was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of two species, and deletion of one species. This article presents the updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV).

IntroductionOur research group and others demonstrated the implication of the human endogenous retroviruses (HERVs) in SARS-CoV-2 infection and their association with disease progression, suggesting HERVs as contributing factors in COVID-19 immunopathology. To identify early predictive biomarkers of the COVID-19 severity, we analyzed the expression of HERVs and inflammatory mediators in SARS-CoV-2-positive and -negative nasopharyngeal/oropharyngeal swabs with respect to biochemical parameters and clinical outcome.MethodsResiduals of swab samples (20 SARS-CoV-2-negative and 43 SARS-CoV-2-positive) were collected during the first wave of the pandemic and expression levels of HERVs and inflammatory mediators were analyzed by qRT-Real time PCR.ResultsThe results obtained show that infection with SARS-CoV-2 resulted in a general increase in the expression of HERVs and mediators of the immune response. In particular, SARS-CoV-2 infection is associated with increased expression of HERV-K and HERV-W, IL-1β, IL-6, IL-17, TNF-α, MCP-1, INF-γ, TLR-3, and TLR-7, while lower levels of IL-10, IFN-α, IFN-β, and TLR-4 were found in individuals who underwent hospitalization. Moreover, higher expression of HERV-W, IL-1β, IL-6, IFN-α, and IFN-β reflected the respiratory outcome of patients during hospitalization. Interestingly, a machine learning model was able to classify hospitalized vs not hospitalized patients with good accuracy based on the expression levels of HERV-K, HERV-W, IL-6, TNF-a, TLR-3, TLR-7, and the N gene of SARS-CoV-2. These latest biomarkers also correlated with parameters of coagulation and inflammation.DiscussionOverall, the present results suggest HERVs as contributing elements in COVID-19 and early genomic biomarkers to predict COVID-19 severity and disease outcome.

Abstract The importance of cryptocurrency to the global economy is increasing steadily, which is evidenced by a total market capitalization of over $2.18T as of December 17, 2021, according to coinmarketcap.com (Coin, 2021). Cryptocurrencies are too confusing for laymen and require more investigation. In this study, we analyze the impact that the effective reproductive rate, an epidemiological indicator of the spread of COVID-19, has on both the price and trading volume of eight of the largest digital currencies—Bitcoin, Ethereum, Tether, Ripple, Litecoin, Bitcoin Cash, Cardano, and Binance. We hypothesize that as the rate of spread decreases, the trading price of the digital currency increases. Using Generalized Autoregressive Conditional Heteroskedasticity models, we find that the impact of the spread of COVID-19 on the price and trading volume of cryptocurrencies varies by currency and region. These findings offer novel insight into the cryptocurrency market and the impact that the viral spread of COVID-19 has on the value of the major cryptocurrencies.

Despite the high impact of the COVID-19 pandemic on social interactions and healthcare workers’ (HWs’) mental health, few studies have investigated the association between social network characteristics and HWs’ mental health, particularly during the pandemic. Therefore, we aimed to assess the associations between public health residents’ (PHRs’) social network characteristics and depression. We used data from the Public Health Residents’ Anonymous Survey in Italy (PHRASI), a nationwide cross-sectional study. Social network characteristics were self-reported. Depressive symptoms were assessed using the nine-item Patient Health Questionnaire. Linear and logistic models adjusted for age, sex, physical activity, and alcohol were used. A moderation analysis by sex was also performed. A total of 379 PHRs participated in the survey (58% females, median age of 30 years). More peer-to-peer (odds ratio OR = 0.62 (0.47–0.83)) and supervisor support (OR = 0.49 (0.36–0.68)), more social participation ((OR) = 0.36 95% CI (0.25–0.50)), and having a partner (OR = 0.49 (0.25–0.96)) were significantly associated with a lower risk of clinically relevant depressive symptoms. Work-to-private-life interference was significantly associated with a higher risk of clinically relevant depressive symptoms (OR = 1.77 (1.28–2.45)). Promoting a supportive work environment and social participation as well as reducing work-to-private life interference can contribute to reducing the high burden among PHRs.

Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some clinical features overlapping with Kawasaki disease (KD). Our research group and others have highlighted that the spike protein of SARS-CoV-2 can trigger the activation of human endogenous retroviruses (HERVs), which in turn induces inflammatory and immune reactions, suggesting HERVs as contributing factors in COVID-19 immunopathology. With the aim to identify new factors involved in the processes underlying KD and MIS-C, we analysed the transcriptional levels of HERVs, HERV-related genes, and immune mediators in children during the acute and subacute phases compared with COVID-19 paediatric patients and healthy controls. The results showed higher levels of HERV-W, HERV-K, Syn-1, and ASCT-1/2 in KD, MIS-C, and COV patients, while higher levels of Syn-2 and MFSD2A were found only in MIS-C patients. Moreover, KD and MIS-C shared the dysregulation of several inflammatory and regulatory cytokines. Interestingly, in MIS-C patients, negative correlations have been found between HERV-W and IL-10 and between Syn-2 and IL-10, while positive correlations have been found between HERV-K and IL-10. In addition, HERV-W expression positively correlated with the C-reactive protein. This pilot study supports the role of HERVs in inflammatory diseases, suggesting their interplay with the immune system in this setting. The elevated expression of Syn-2 and MFSD2A seems to be a distinctive trait of MIS-C patients, allowing to distinguish them from KD ones. The understanding of pathological mechanisms can lead to the best available treatment for these two diseases, limiting complications and serious outcomes.

The COVID-19 pandemic caused a reduction in vaccination coverage for all age groups, especially in non-infant age. The main objective of the present study is to evaluate the effectiveness of an online intervention conducted among adolescents during the COVID-19 pandemic in increasing knowledge and positive attitudes toward vaccinations. The study, which took place online from March to May 2021, involved 267 students from six lower secondary schools in Palermo city (Italy); they filled out the questionnaire before and after the intervention. The questionnaire was based on the protection motivation theory (PMT), which estimates the improvement in vaccination-related knowledge and attitudes. The pre- and post-intervention comparison showed a significant increase in the perception of the disease severity: strongly agree pre-intervention n = 150 (58.6%) and post-intervention n = 173 (67.6%, p < 0.001), rated on a five-point Likert scale. In a multivariate analysis, the factor associated with the improvement in the score after the intervention was the school dropout index (low vs. very high dropout index OR 4.5; p < 0.03). The educational intervention was more effective in schools with lower early school leaving rates, an indirect index of socio-economic status. The topic of vaccination has caught the adolescents’ attention, it is, therefore, important that interventions tackling teenagers are tailored to reduce their emotional tension about the perception of adverse effects and improve vaccination coverage.

In last years, coreference resolution has received a sensibly performance boost exploiting different pre-trained Neural Language Models, from BERT to SpanBERT until Longformer. This work is aimed at assessing, for the first time, the impact of ELECTRA model on this task, moved by the experimental evidence of an improved contextual representation and better performance on different downstream tasks. In particular, ELECTRA has been employed as representation layer in an assessed neural coreference architecture able to determine entity mentions among spans of text and to best cluster them. The architecture itself has been optimized: i) by simplifying the modality of representation of spans of text but still considering both the context they appear and their entire content, ii) by maximizing both the number and length of input textual segments to exploit better the improved contextual representation power of ELECTRA, iii) by maximizing the number of spans of text to be processed, since potentially representing mentions, preserving computational efficiency. Experimental results on the OntoNotes dataset have shown the effectiveness of this solution from both a quantitative and qualitative perspective, and also with respect to other state-of-the-art models, thanks to a more proficient token and span representation. The results also hint at the possible use of this solution also for low-resource languages, simply requiring a pre-trained version of ELECTRA instead of language-specific models trained to handle either spans of text or long documents.

PIN1 is considered as a therapeutic target for a wide variety of tumours. However, most of known inhibitors are devoid of cellular activity despite their good enzyme inhibitory profile. Hence, the lack of effective compounds for the clinic makes the identification of novel PIN1 inhibitors a hot topic in the medicinal chemistry field. In this work, we reported a virtual screening study for the identification of new promising PIN1 inhibitors. A receptor-based procedure was applied to screen different chemical databases of commercial compounds. Based on the whole workflow, two compounds were selected and biologically evaluated. Both ligands, compounds VS1 and VS2, showed a good enzyme inhibitory activity and VS2 also demonstrated a promising antitumoral activity in ovarian cancer cells. These results confirmed the reliability of our in silico protocol and provided a structurally novel ligand as a valuable starting point for the development of new PIN1 inhibitors.

Recently, many approaches were proposed to support human resource management in finding the best human resources for available jobs. However, existing solutions do not effectively evaluate employees’ skills, or they do only partially, neither provide mechanisms to describe subjects’ skills and desiderata. To face this issue, this paper proposes a decision model for assisting human resource management in effectively evaluating the degree of mutual satisfaction in job-employee assignments. In particular, the decision model has been devised with the following core characteristics: i) employees’ skills are modeled by combining hard skills (e.g.: academic training and competencies) and soft skills (e.g.: socio-relational experiences); ii) employees’ soft skills are self-evaluated, giving importance not so much to experiences possessed but rather how such skills have been applied over time; iii) employees and managers can self-evaluate their preferences to enable the achievement of the optimal allocation by maximizing the global mutual satisfaction iv) partial matches between characteristics and desires of both employees and jobs are measured through a set of tailored fuzzy metrics. The proposed decision model has been validated in a real case to support the allocation of newly hired employees among open job positions in a Public Administration. Results showed an adequate ability of the proposed model both to support the description of employees, skills, jobs and preferences, and to suggest the best allocation maximizing the global mutual satisfaction. Summarizing, a decision model for human resource management with innovative characteristics is proposed and used to support decisions for a real allocation problem.

Raoul Emeric Guetiya Wadoum,1 Stephen Sevalie,2 Antonella Minutolo,3 Andrew Clarke,4,5 Gianluca Russo,6 Vittorio Colizzi,7 Maurizio Mattei,8 Carla Montesano8 1Department of Public Health, Microbiology and Immunology, Ernest Bai Koroma University of Science and Technology, Makeni, Sierra Leone; 2 34th Regimental Military Hospital, The Republic of Sierra Leone Armed Forces, Freetown, Sierra Leone; 3Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy; 4Global Programs Division, Save the Children United Kingdom, London, UK; 5Division of Health Research, Lancaster University, Lancaster, UK; 6Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy; 7Department of Biomedical Sciences, Faculty of Science and Technology, Evangelical University of Cameroon, Bandjoun, Cameroon; 8Department of Biology, School of Mathematics, Physics and Natural Sciences, University of Rome Tor Vergata, Rome, ItalyCorrespondence: Raoul Emeric Guetiya Wadoum Tel +232 78425924Email ergwadoum@ebkustsl.edu.sl; raoulemeric@gmail.comAbstract: The Ebola virus disease, formerly known as Ebola hemorrhagic fever, is a severe and often fatal zoonosis in humans. The 2013– 2016 West African Ebola outbreak had distinctive characteristics, and it was the largest and most complex epidemic since the virus discovery in 1976. Although the 2018– 2020 Ebola outbreak in the Democratic Republic of the Congo had many similarities, there were additional challenges due to the presence of armed rebel groups at the epicenters of the epidemic. Despite these challenges, the extraordinary commitment of the World Health Organization (WHO) regional office for Africa, in collaboration with Africa Union (AU) member states through the Africa Centres for Disease Control and Prevention (Africa CDC), and WHO’s prompt declaration of a Public Health Emergency of International Concern (PHEIC) shepherded an effective coordinated response to contain the epidemic. Learning from previous Ebola virus epidemics and the current Coronavirus disease 2019 (COVID-19) pandemic, the AU member states should strengthen inter-state coordination towards the development and implementation of a preparedness and readiness plan which will enable the continent to build and sustain resilient capacities to prevent, detect, and respond to future outbreaks following the International Health Regulations (IHR).Keywords: United Nations, Africa Union, WHO, Africa CDC, Ebola virus disease, COVID-19

A balanced diet is critical for human health, and edible plants play an important role in providing essential micronutrients as well as specific microRNAs (miRNAs) that can regulate human gene expression. Here we present the effects of Moringa oleifera (MO) miRNAs (mol-miRs) on lipid metabolism. Through in silico studies we identified the potential genes involved in lipid metabolism targeted by mol-miRs. To this end, we tested the efficacy of an aqueous extract of MO seeds (MOES), as suggested in traditional African ethnomedicine, or its purified miRNAs. The biological properties of MO preparations were investigated using a human derived hepatoma cell line (HepG2) as a model. MOES treatment decreased intracellular lipid accumulation and induced apoptosis in HepG2. In the same cell line, transfection with mol-miRs showed similar effects to MOES. Moreover, the effect of the mol-miR pool was investigated in a pre-obese mouse model, in which treatment with mol-miRs was able to prevent dysregulation of lipid metabolism.

Hydrodynamic cavitation (HC), as an effective, efficient, and scalable extraction technique for natural products, could enable the affordable production of valuable antioxidant extracts from plant resources. For the first time, whole pomegranate (Punica granatum L.) fruits, rich in bioactive phytochemicals endowed with anti-cancer properties, were extracted in water using HC. Aqueous fractions sequentially collected during the process (M1–M5) were lyophilized (L), filtered (A), or used as such, i.e., crude (C), and analyzed for their biochemical profile and in vitro antioxidant power. The fractions M3 and M4 from the L and C series showed the highest antiradical activity and phytochemical content. While the lyophilized form is preferable for application purposes, sample L-M3, which was produced faster and with lower energy consumption than M4, was used to assess the potential antiproliferative effect on human breast cancer line (AU565-PAR) and peripheral blood mononuclear (PBMC) cells from healthy donors. In a pilot study, cell growth, death, and redox state were assessed, showing that L-M3 significantly reduced tumor cell proliferation and intracellular oxygen reactive species. No effect on PBMCs was detected. Thus, the antioxidant phytocomplex extracted from pomegranate quickly (15 min), at room temperature (30 °C), and efficiently showed potential anticancer activity without harming healthy cells.

Abstract Background Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. Methods Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure 40/50 mg/dL for men/women and

Upwelling of nutrient-rich deep waters make eastern boundary upwelling systems (EBUSs), such as the Humboldt Current system, hot spots of marine productivity. Associated settling of organic matter to depth and consecutive aerobic decomposition results in large subsurface water volumes being oxygen depleted. Under these circumstances, organic matter remineralisation can continue via denitrification, which represents a major loss pathway for bioavailable nitrogen. Additionally, anaerobic ammonium oxidation can remove significant amounts of nitrogen in these areas. Here we assess the interplay of suboxic water upwelling and nitrogen cycling in a manipulative offshore mesocosm experiment. Measured denitrification rates in incubations with water from the oxygen-depleted bottom layer of the mesocosms (via 15N label incubations) mostly ranged between 5.5 and 20 nmol N2 L−1 h−1 (interquartile range), reaching up to 80 nmol N2 L−1 h−1. However, actual in situ rates in the mesocosms, estimated via Michaelis–Menten kinetic scaling, did most likely not exceed 0.2–4.2 nmol N2 L−1 h−1 (interquartile range) due to substrate limitation. In the surrounding Pacific, measured denitrification rates were similar, although indications of substrate limitation were detected only once. In contrast, anammox (anaerobic ammonium oxidation) made only a minor contribution to the overall nitrogen loss when encountered in both the mesocosms and the Pacific Ocean. This was potentially related to organic matter C / N stoichiometry and/or process-specific oxygen and hydrogen sulfide sensitivities. Over the first 38 d of the experiment, total nitrogen loss calculated from in situ rates of denitrification and anammox was comparable to estimates from a full nitrogen budget in the mesocosms and ranged between ∼ 1 and 5.5 µmol N L−1. This represents up to ∼ 20 % of the initially bioavailable inorganic and organic nitrogen standing stocks. Interestingly, this loss is comparable to the total amount of particulate organic nitrogen that was exported into the sediment traps at the bottom of the mesocosms at about 20 m depth. Altogether, this suggests that a significant portion, if not the majority of nitrogen that could be exported to depth, is already lost, i.e. converted to N2 in a relatively shallow layer of the surface ocean, provided that there are oxygen-deficient conditions like those during coastal upwelling in our study. Published data for primary productivity and nitrogen loss in all EBUSs reinforce such conclusion.

The effect of oxidation on nascent soot particles is investigated in this work by means of Raman spectroscopy. Three different soot particle samples are produced in a lightly sooting ethylene/air laminar premixed flame and collected at different residence times. The samples are characterized by a different size of primary particles and a different degree of aging and hence graphitization, and they are representative of the early evolution of nascent soot in flames. Oxidation of particles is induced by exposing the samples to a high temperature oxidation treatment in air over a range of temperature 25–500°C. To this aim, a programmable heating microscope stage is used. Thermo-optical transmission (TOT) measurements are used to characterize the chemical composition of pristine particles in terms of organic and elemental carbon content, also providing the pyrolytic carbon fraction of the organic carbon. The TOT results show that the organic fraction is constant for the three conditions. On the other hand, the pyrolytic carbon fraction decreases and the elemental carbon increases when moving from the sample composed of just-nucleated particles to the sample mostly made of mature soot particles. Raman spectroscopy reveals that the thermal oxidation treatment performed on the sample of just-nucleated particles, with the highest organic carbon content, results in a reduction of the amorphous carbon component. Conversely, the sample of mature soot, with the highest elemental carbon content, shows an increase in the amorphous carbon phase after oxidation, which is attributed to fragmentation or the formation of point defects by O2 oxidation. Finally, the thermal oxidation procedure produces a strong reduction in the photoluminescence signal detected from Raman spectra.

Metal-derived platinum complexes are widely used to treat solid tumors. However, systemic toxicity and tumor resistance to these drugs encourage further research into similarly effective compounds. Among others, organotin compounds have been shown to inhibit cell growth and induce cell death and autophagy. Nevertheless, the impact of the ligand structure and mechanisms involved in the toxicity of organotin compounds have not been clarified. In the present study, the biological activities of commercially available bis(tributyltin) oxide and tributyltin chloride, in comparison to those of specially synthesized tributyltin trifluoroacetate (TBT-OCOCF3) and of cisplatin, were assessed using cells with different levels of tumorigenicity. The results show that tributyltins were more cytotoxic than cisplatin in all the tested cell lines. NMR revealed that this was not related to the interaction with DNA but to the inhibition of glucose uptake into the cells. Moreover, highly tumorigenic cells were less susceptible than nontumorigenic cells to the nonunique pattern of death induced by TBT-OCOCF3. Nevertheless, tumorigenic cells became sensitive when cotreated with wortmannin and TBT-OCOCF3, although no concomitant induction of autophagy by the compound was detected. Thus, TBT-OCOCF3 might be the prototype of a family of potential anticancer agents.

Malignant mesothelioma (MM) is a highly aggressive and resistant tumor. The prognostic role of key effectors of glycolytic metabolism in MM prompted our studies on the cytotoxicity of new inhibitors of glucose transporter type 1 (GLUT-1) and lactate dehydrogenase-A (LDH-A) in relation to ATP/NAD+ metabolism, glycolysis and mitochondrial respiration. The antiproliferative activity of GLUT-1 (PGL13, PGL14) and LDH-A (NHI-1, NHI-2) inhibitors, alone and in combination, were tested with the sulforhodamine-B assay in peritoneal (MESO-II, STO) and pleural (NCI-H2052 and NCI-H28) MM and non-cancerous (HMEC-1) cells. Effects on energy metabolism were measured by both analysis of nucleotides using RP-HPLC and evaluation of glycolysis and respiration parameters using a Seahorse Analyzer system. All compounds reduced the growth of MM cells in the µmolar range. Interestingly, in H2052 cells, PGL14 decreased ATP concentration from 37 to 23 and NAD+ from 6.5 to 2.3 nmol/mg protein. NHI-2 reduced the ATP/ADP ratio by 76%. The metabolic effects of the inhibitors were stronger in pleural MM and in combination, while in HMEC-1 ATP reduction was 10% lower compared to that of the H2052 cells, and we observed a minor influence on mitochondrial respiration. To conclude, both inhibitors showed cytotoxicity in MM cells, associated with a decrease in ATP and NAD+, and were synergistic in the cells with the highest metabolic modulation. This underlines cellular energy metabolism as a potential target for combined treatments in selected cases of MM.

The prevalence of recovery of kidney function (RKF) in patients under maintenance dialysis is poorly defined mainly because of different definitions of RKF. Therefore, to gain more insights into the epidemiology of RKF, we performed a systematic review and meta-analysis of studies addressing the prevalence of sustained (at least for 30 days) RKF in patients under maintenance dialysis. Acute kidney injury (AKI) and RKF in the first 90 days of dialysis were the main exclusion criteria. Overall, 7 studies (10 cohorts) including 2,444,943 chronic dialysis patients (range: 430–1,900,595 patients) were meta-analyzed. The period of observation ranged from 4 to 43 years. The prevalence of RKF was 1.49% (95% C.I.:1.05–2.11; p < 0.001] with high heterogeneity I2: 99.8%, p < 0.001. The weighted mean dialysis vintage before RKF was 294 ± 165 days; RKF persisted for a weighted mean of 27.5 months. The percentage of RKF was higher in studies from the U.S. (1.96% [95% C.I.: 1.24–3.07]) as compared to other countries (1.04% [95%C.I.: 0.66–1.62]; p = 0.049). In conclusion, sustained RKF unrelated to AKI occurs in about 1.5% of patients under maintenance dialysis. On average, RKF patients discontinue chronic dialysis about ten months after starting treatment and live free of dialysis for more than two years. The higher prevalence of RKF reported in the U.S. versus other countries suggests a major role of country-specific policies for dialysis start.

Several strategies have been attempted to target immune suppressive populations in the tumor microenvironment. Here the authors show that folate receptor β-targeted CAR-T cells eliminate immunosuppressive tumor associated macrophages, promoting endogenous antitumor immune responses and adoptive T-cell therapy in pre-clinical models.

In recent years, the impact of Neural Language Models has changed every field of Natural Language Processing. In this scenario, coreference resolution has been among the least considered task, especially in language other than English. This work proposes a coreference resolution system for Italian, based on a neural end-to-end architecture integrating ELECTRA language model and trained on OntoCorefIT, a novel Italian dataset built starting from OntoNotes. Even if some approaches for Italian have been proposed in the last decade, to the best of our knowledge, this is the first neural coreference resolver aimed specifically to Italian. The performance of the system is evaluated with respect to three different metrics and also assessed by replacing ELECTRA with the widely-used BERT language model, since its usage has proven to be effective in the coreference resolution task in English. A qualitative analysis has also been conducted, showing how different grammatical categories affect performance in an inflectional and morphological-rich language like Italian. The overall results have shown the effectiveness of the proposed solution, providing a baseline for future developments of this line of research in Italian.