ABSTRACT In recent years, the increasing precision of direct cosmic rays measurements opened the door to high-sensitivity indirect searches of dark matter and to more accurate predictions for ...radiation doses received by astronauts and electronics in space. The key ingredients in the study of these phenomena are the knowledge of the local interstellar spectrum (LIS) of galactic cosmic rays and the understanding of how the solar modulation affects the LIS inside the heliosphere. Voyager 1, AMS-02, PAMELA, and BESS measurements of proton and helium fluxes provide valuable information, allowing us to shed light on the shape of the LIS and the details of the solar modulation during solar cycles 22-24. A new parametrization of the LIS is presented, based on the latest data from Voyager 1 and AMS-02. Using the framework of the force-field approximation, the solar modulation parameter is extracted from the time-dependent fluxes measured by PAMELA and BESS. A modified version of the force-field approximation with a rigidity-dependent modulation parameter is introduced, yielding better fits than the force-field approximation. The results are compared with the modulation parameter inferred by neutron monitors.
Coronavirus disease 2019 (COVID-19) has affected >210 million people worldwide. An optimal therapeutic approach for COVID-19 remains uncertain, to date. Since the history of cancer was linked to ...higher mortality rates due to COVID-19, the establishment of a safe and effective vaccine coverage is crucial in these patients. However, patients with cancer (PsC) were mostly excluded from vaccine candidates' clinical trials. This systematic review aims to investigate the current available evidence about the immunogenicity of COVID-19 vaccines in PsC.
All prospective studies that evaluated the safety and efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included, with immunogenicity after the first and the second dose as the primary endpoint, when available.
Vaccination against COVID-19 for PsC seems overall safe and immunogenic after well-conducted vaccination schedules. Yet the seroconversion rate remains lower, lagged or both compared to the general population. Patients with hematologic malignancies, especially those receiving B-cell-depleting agents in the past 12 months, are the most at risk of poor seroconversion.
A tailored approach to vaccination may be proposed to PsC, especially on the basis of the type of malignancy and of the specific oncologic treatments received.
•History of cancer is linked to higher mortality rates due to COVID-19.•Data on the immunogenicity of COVID-19 vaccines in PsC are scarce.•This review included prospective studies that evaluated immunogenicity of vaccines against COVID-19 in PsC.•Vaccination seems overall safe and immunogenic after well-conducted vaccination schedules.•Hematologic patients receiving B-cell-depleting agents in the last 12 months are the most at risk of poor seroconversion.
Cancer vaccines (CVs) represent a long-sought therapeutic and prophylactic immunotherapy strategy to obtain antigen (Ag)-specific T-cell responses and potentially achieve long-term clinical benefit. ...However, historically, most CV clinical trials have resulted in disappointing outcomes, despite promising signs of immunogenicity across most formulations. In the past decade, technological advances regarding vaccine delivery platforms, tools for immunogenomic profiling, and Ag/epitope selection have occurred. Consequently, the ability of CVs to induce tumor-specific and, in some cases, remarkable clinical responses have been observed in early-phase clinical trials. It is notable that the record-breaking speed of vaccine development in response to the coronavirus disease-2019 pandemic mainly relied on manufacturing infrastructures and technological platforms already developed for CVs. In turn, research, clinical data, and infrastructures put in place for the severe acute respiratory syndrome coronavirus 2 pandemic can further speed CV development processes. This review outlines the main technological advancements as well as major issues to tackle in the development of CVs. Possible applications for unmet clinical needs will be described, putting into perspective the future of cancer vaccinology.
•CVs have been characterized by positive safety and immunogenicity profiles but low levels of clinical efficacy.•Novel CV strategies entail personalized formulations and effective combinatorial regimens.•Positive momentum from the coronavirus disease-2019 vaccination campaign can in turn accelerate CV clinical testing.
•We explored the role of adjuvant chemotherapy in the treatment of patients with localized lobular breast cancer (ILC)?•In this systematic review of the literature and metanalysis, a role of the ...adjuvant chemotherapy in the setting of ILC was not confirmed. The analysis on 38,387 patients across 8 studies did not show an additional benefit of chemotherapy (Hazard Ratio for Overall Survival: 0.99; 95%CI 0.86–1.14). However, all the investigations were retrospective, and subgroup analyses in high-risk patients showed some signals of possible adjunctive benefits.•Prospective investigations of adjuvant therapies in high-risk patients with ILC are highly warranted. The current decision- making is largely based on evidence from non-randomized clinical investigations, prompting controlled clinical studies.
The role of adjuvant chemotherapy (aCT) for patients with localized lobular breast cancer (ILC) is still controversial. It is unclear what is the magnitude of benefit of the CT in this setting. In this systematic review of the literature and metanalysis, we aimed to estimate the benefit of aCT in addition to the standard treatments in the early ILC setting. We identified the records by searching Medline, CENTRAL, Web of Science, SCOPUS, and Google Scholar, and the meeting proceeding of the principal oncology meetings of the last 10 years, with no language or time restriction. A research strategy was developed with mapped and MeSH terms. Studies on the clinical use of aCT reporting survival outcomes in the ILC setting were double-screened and tabulated. PRISMA methodology was used for data extraction and synthesis. We extracted information on the study design and setting, eligible population and population size, histology variants, menopausal status, treatment regimens, follow-up duration. Hazard ratios (HR) and 95% confidence interval (CI) were extracted and transformed into logHR and corresponding standard error to obtain the Summary HR (SHR). Heterogeneity (I2 statistics) and publication bias (Macaskill test) were tested; a random effect models provided by SAS Proc Mixed was used for data analysis. Sensitivity analysis was conducted to examine the impact of inclusion criteria on the summary results.
Disease-free (DFS), overall (OS) and cancer-specific survival (BCSS) were the primary endpoints of the investigation. The systematic review and metanalysis included 38,387 patients across 8 clinical studies. aCT was not associated with an improvement of OS (SHR 0.99; 95%CI 0.86–1.14), with low heterogeneity (I2 = 28%) and no publication bias (p = 0.43). Sensitivity analysis resulted in unchanged conclusions. We did not perform a metanalysis of the DFS estimates, as only reported in 3 studies. The value of aCT in improving DFS was unconfirmed, consistently with the OS results. Our research did not confirm a certain role of aCT for patients with ILC. Research gaps were identified, warranting the development of prospective, controlled ad hoc investigations.
The host immune status is critical for preventing opportunistic infections with Candida albicans. Whether the natural fungal diversity that exists between C. albicans isolates also influences disease ...development remains unclear. Here, we used an experimental model of oral infection to probe the host response to diverse C. albicans isolates in vivo and found dramatic differences in their ability to persist in the oral mucosa, which inversely correlated with the degree and kinetics of immune activation in the host. Strikingly, the requirement of interleukin (IL)-17 signaling for fungal control was conserved between isolates, including isolates with delayed induction of IL-17. This underscores the relevance of IL-17 immunity in mucosal defense against C. albicans. In contrast, the accumulation of neutrophils and induction of inflammation in the infected tissue was strictly strain dependent. The dichotomy of the inflammatory neutrophil response was linked to the capacity of fungal strains to cause cellular damage and release of alarmins from the epithelium. The epithelium thus translates differences in the fungus into qualitatively distinct host responses. Altogether, this study provides a comprehensive understanding of the antifungal response in the oral mucosa and demonstrates the relevance of evaluating intraspecies differences for the outcome of fungal-host interactions in vivo.
A new era in cosmic rays physics has started thanks to the precise and continuous observations from space experiments such as PAMELA and AMS-02. Invaluable results are coming out from these new data ...that are rewriting the theory of acceleration and propagation of cosmic rays. Both at high energies, where several new behaviors have been measured, challenging the accuracy of theoretical models, and also at low energies, in the region affected by the solar modulation. Precise measurements are increasing our knowledge of the effects of solar modulation on low energy cosmic rays, allowing a detailed study of propagation and composition as it has never been done before. These measurements will serve as a high-precision baseline for continued studies of GCR composition, GCR modulation over the solar cycle, space radiation hazards, and other topics.
In this review paper, the status of the latest measurements of the cosmic rays in the context of solar modulation are presented together with the current open questions and the future prospects. How new measurements from the AMS-02 experiment will address these questions is also discussed.
Aims
This study reports the results of the application of a new agar‐gauze biogel system activated with viable bacterial cells to altered wall paintings.
Methods and Results
Biocleaning using agar ...biogel and agar‐gauze biogel systems was performed onsite by direct application to altered wall painting surfaces (25–1000 cm2). The treatments were performed for the restoration of two original Italian sites: (i) at the Vatican Museums, Cristo che salva Pietro dalle acque—La Navicella, a wall painting by Giovanni Lanfranco (1627–1628) and (ii) at Pisa Cathedral Cupola, Incarnato, a wall painting by Orazio Riminaldi (1593–1630) and his brother Girolamo Riminaldi. The novelty of this study is the use of viable Pseudomonas stutzeri A29 cells in an advanced agar‐gauze biogel system and the short bio‐application contact times of between 3 and 12 h. The historical artworks were altered by lipid and protein residues from past restoration, as confirmed by Py‐gas chromatography–mass spectrometry and FT‐IR data. The effectiveness of the biological treatment was assessed, and general considerations were discussed.
Conclusions
The short bio‐application contact time of advanced agar‐gauze gel activated with viable P. stutzeri cells makes this biotechnology promising as an alternative method to the traditional onsite cleaning techniques currently in use for altered historical wall paintings.
Significance and Impact of the Study
In this study, we report for the first time the biocleaning of altered materials located in vertical and vaulted areas using agar‐gauze biogel with short application times. These findings are of great significance for future restoration activities and are crucial for determining the best preservation strategies in this field.
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