VariantHunter: a method and tool for fast detection of emerging SARS-CoV-2 variants

With the progression of the COVID-19 pandemic, large datasets of SARS-CoV-2 genome sequences were collected to closely monitor the evolution of the virus and identify the novel variants/strains. By analyzing genome sequencing data, health authorities can 'hunt' novel emerging variants of SARS-CoV-2 as early as possible, and then monitor their evolution and spread. We designed VariantHunter, a highly flexible and user-friendly tool for systematically monitoring the evolution of SARS-CoV-2 at global and regional levels. In VariantHunter, amino acid changes are analyzed over an interval of 4 weeks in an arbitrary geographical area (continent, country, or region); for every week in the interval, the prevalence is computed and changes are ranked based on their increase or decrease in prevalence. VariantHunter supports two main types of analysis: lineage-independent and lineage-specific. The former considers all the available data and aims to discover new viral variants. The latter evaluates specific lineages/viral variants to identify novel candidate designations (sub-lineages and sub-variants). Both analyses use simple statistics and visual representations (diffusion charts and heatmaps) to track viral evolution. A dataset explorer allows users to visualize available data and refine their selection. VariantHunter is a web application free to all users. The two types of supported analysis (lineage-independent and lineage-specific) allow user-friendly monitoring of the viral evolution, empowering genomic surveillance without requiring any computational background. Database URL http://gmql.eu/variant_hunter/

A case of central venous catheter-related Candida parapsilosis fungemia evolved to disseminated infection in a neutropenic patient with blast crisis of chronic myeloid leukemia.

Central venous catheter-related infections are of particular importance in onco-hematological patients. Candida parapsilosis is generally reported as a mild pathogen, however it is able to effectively colonize intravascular devices and potentially give rise to sustained fungemias. Here we report a case of invasive, potentially lethal C. parapsilosis disseminated infection in a neutropenic patient affected by chronic myeloid leukemia with blast crisis. We underline the importance of removing the central venous catheter as potential source of infection as soon as possible during the course of candidemia, and not replacing it with other polyurethan intravascular devices, which pose a risk for the maintenance of the fungemia despite the administration of the best antifungal therapy available

Defective One- or Two-electron Reduction of the Anticancer Anthracycline Epirubicin in Human Heart RELATIVE IMPORTANCE OF VESICULAR SEQUESTRATION AND IMPAIRED EFFICIENCY OF ELECTRON ADDITION

One-electron quinone reduction and two-electron carbonyl reduction convert the anticancer anthracycline doxorubicin to reactive oxygen species (ROS) or a secondary alcohol metabolite that contributes to inducing a severe form of cardiotoxicity. The closely related analogue epirubicin induces less cardiotoxicity, but the determinants of its different behavior have not been elucidated. We developed a translational model of the human heart and characterized whether epirubicin exhibited a defective conversion to ROS and secondary alcohol metabolites. Small myocardial samples from cardiac surgery patients were reconstituted in plasma that contained clinically relevant concentrations of doxorubicin or epirubicin. In this model only doxorubicin formed ROS, as detected by fluorescent probes or aconitase inactivation. Experiments with cell-free systems and confocal laser scanning microscopy studies of H9c2 cardiomyocytes suggested that epirubicin could not form ROS because of its protonation-dependent sequestration in cytoplasmic acidic organelles and the consequent limited localization to mitochondrial one-electron quinone reductases. Accordingly, blocking the protonation-sequestration mechanism with the vacuolar H+-ATPase inhibitor bafilomycin A1 relocalized epirubicin to mitochondria and increased its conversion to ROS in human myocardial samples. Epirubicin also formed ∼60% less alcohol metabolites than doxorubicin, but this was caused primarily by its higher Km and lower Vmax values for two-electron carbonyl reduction by aldo/keto-reductases of human cardiac cytosol. Thus, vesicular sequestration and impaired efficiency of electron addition have separate roles in determining a defective bioactivation of epirubicin to ROS or secondary alcohol metabolites in the human heart. These results uncover the molecular determinants of the reduced cardiotoxicity of epirubicin and serve mechanism-based guidelines to improving antitumor therapies

Healthcare Service Quality Evaluation in a Community-Oriented Primary Care Center, Italy

Community-oriented primary care (COPC) is an inclusive healthcare approach that combines individual care with a population-based outlook, striving to offer effective and equitable services. This study concentrates on assessing the perceived quality of a "Casa della Comunita" (CdC) implemented by the Romagna Local Health Authority, which embraces the COPC model. Through the examination of user experiences, the study aims to comprehend the influence of the CdC's care delivery model on the community's perception of service quality. From 13-18 March 2023, paper questionnaires were distributed by trained healthcare professionals and volunteers. The cross-sectional study enrolled participants aged 18 or older, capable of understanding written Italian, and willing to take part voluntarily. A total of 741 questionnaires were collected, resulting in an overall acceptance rate of 85.6%. Among the respondents, 37.9% were female, with an average age of 55.4 & PLUSMN; 16.2 years. While the respondents generally held a positive view of the quality, the results displayed varying levels of satisfaction across the different areas. Multivariate analysis revealed significant associations between factors such as gender, employment status, financial resources, education level, and distance from the healthcare center with the perceived quality of the facility in terms of accessibility, environment, staff, continuity of care, and overall satisfaction. The study yielded valuable insights, identifying strengths and areas for improvement and underscoring the importance of ongoing monitoring studies to enhance patient satisfaction continuously

Report on the International Colloquium on Cardio-Oncology (Rome, 12–14 March 2014)

Cardio-oncology is a relatively new discipline that focuses on the cardiovascular sequelae of anti-tumour drugs. As any other young adolescent discipline, cardio-oncology struggles to define its scientific boundaries and to identify best standards of care for cancer patients or survivors at risk of cardiovascular events. The International Colloquium on Cardio-Oncology was held in Rome, Italy, 12–14 March 2014, with the aim of illuminating controversial issues and unmet needs in modern cardio-oncology. This colloquium embraced contributions from different kind of disciplines (oncology and cardiology but also paediatrics, geriatrics, genetics, and translational research); in fact, cardio-oncology goes way beyond the merging of cardiology with oncology. Moreover, the colloquium programme did not review cardiovascular toxicity from one drug or the other, rather it looked at patients as we see them in their fight against cancer and eventually returning to everyday life. This represents the melting pot in which anti-cancer therapies, genetic backgrounds, and risk factors conspire in producing cardiovascular sequelae, and this calls for screening programmes and well-designed platforms of collaboration between one key professional figure and another. The International Colloquium on Cardio-Oncology was promoted by the Menarini International Foundation and co-chaired by Giorgio Minotti (Rome), Joseph R Carver (Philadelphia, Pennsylvania, United States), and Steven E Lipshultz (Detroit, Michigan, United States). The programme was split into five sessions of broad investigational and clinical relevance (what is cardiotoxicity?, cardiotoxicity in children, adolescents, and young adults, cardiotoxicity in adults, cardiotoxicity in special populations, and the future of cardio-oncology). Here, the colloquium chairs and all the session chairs briefly summarised what was said at the colloquium. Topics and controversies were reported on behalf of all members of the working group of the International Colloquium on Cardio-Oncology

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

A modern Eden: tra città e natura

“A modern Eden” riguarda la città in relazione alla sua evoluzione storica e alla sua situazione attuale. L’approccio progettuale si rifà volutamente alle esperienze radicali degli anni Sessanta e Settanta: l’architettura perde i suoi connotati più concreti divenendo, semplicemente, veicolo di un messaggio. L’esasperazione della forma e le immagini utopiche diventano, quindi, parte integrante di questo procedimento. “A modern Eden” è un progetto che s’inserisce al centro di 16 metropoli del mondo: un grande recinto delimita un gigantesco spazio naturale nel cuore di queste città. Il recinto, alto 110 metri, è un muro abitato che perimetra un’area verde larga 770 metri e suddivisa, tramite terrazzamenti, in porzioni agricole, giardini e un bosco centrale. Questo segno, così forte, insiste principalmente su due temi: quello della natura e quello del limite. Una volta la città era confinata da mura, era riconoscibile, forniva riparo e sicurezza di fronte a un intorno disomogeneo e dominante come la natura. Oggi a essere diventata incontrollata e spaventosa è proprio la città, in particolare nella sua forma metropolitana, a sfavore, chiaramente, dell’aspetto ambientale. L’inquinamento, il consumo di suolo e di risorse sono tematiche tanto attuali quanto preoccupanti. Inserire uno spazio naturale abitabile all’interno di un recinto in mezzo a una metropoli sovverte, in qualche modo l’idea di città, portandoci a chiedere se è possibile, paradossalmente, trovare un nuovo equilibrio di vita nella natura. Allo stesso modo il tema del limite si contrappone agli sviluppi che i nostri sistemi urbani stanno raggiungendo, dimensioni che si estendono oltre i connotati contingenti coinvolgendo flussi economici, dinamiche commerciali, arrivando ai rapporti interpersonali che, ormai, hanno superato il diretto contatto fisico