Search

Multinucleon transfer reactions for the 206Pb +118 Sn system were measured at Elab = 1200 MeV using the PRISMA large solid-angle magnetic spectrometer. The experiment was conducted at laboratory angles around the grazing angle, covering an angular range of approximately 20°. The resulting differential and total cross sections, along with Q-value distributions for various neutron and proton pick-up and stripping channels, are presented. The Q-value distributions suggest a transition from quasi-elastic to deep inelastic collision processes, particularly in channels involving nucleon transfers. The experimental results have been compared with GRAZING code calculations, showing good agreement for few-nucleon transfer channels, while channels with large nucleon transfers are underestimated, indicating the involvement of more complex processes.

In recent years, a number of both theoretical and experimental investigations have been performed focusing on the zirconium isotopic chain. In particular, state-of-the-art Monte Carlo shell-model calculations predict shape coexistence in these isotopes. In this context, the 94Zr nucleus, which is believed to possess a nearly spherical ground state, is particularly interesting since the purported deformed structure is basedon the low-lying 02+ state, making it amenable for detailed study. In order to provide definitive conclusionson the shapes of the low-lying states, two complementary experiments to study 94Zr by means of low-energy Coulomb excitation were performed. This data will allow the quadrupole moments of the 21,2+ levels to be extracted as well as for the deformation parameters of the 01,2+ states to be determined and, thus, definitive conclusions to be drawn on the role of shape coexistence in this nucleus for the first time. The first experiment was performed at the INFN Legnaro National Laboratory with the GALILEO-SPIDER setup, which, for the first time, was coupled with 6 lanthanum bromide scintillators (LaBr3:Ce) in order to maximize the γ-ray detection effciency. The second experiment was performed at the Maier-Leibnitz Laboratory (MLL) in Munich and used a Q3D magnetic spectrograph to detect the scattered 12C ions following Coulomb excitation of 94Zr targets.

A detailed comparative study of the sub-barrier fusion of the two near-by systems 36S+50Ti,51V was performed at the National Laboratories of Legnaro (INFN). Aim of the experiment was the investigation of possible effects of the non-zero spin of the ground state of the 51V nucleus on the sub-barrier excitation function, and in particular on the shape of the barrier distribution. The results sh w that the two measured excitation functions are very similar down to the level of 20 - 30 μb. The same is observed for the two barrier distributions. Coupled-channels calculations have been performed and are in good agreement with the experimental data. This result indicates that the low-lying levels in 51V can be interpreted in the weak-coupling scheme, that is, 51V(I) = 50Ti(2+)⊗ p(1 f7/2).

The presence of seniority-like isomers along the Z = 50 isotopic chain have been an experimental limitation to the investigation of the electromagnetic properties of the low-lying states in the light Sn nuclei. Combining a multi-nucleon transfer reaction with the Recoil-Distance Doppler-Shift technique, the lifetimes of the 21+ and 41+ excited states have been directly measured in the neutron-deficient 106, 108Sn isotopes for the very first time. The emitted γ rays were detected by the AGATA array, while the reactionproducts were uniquely identified by the VAMOS++ magnetic spectrometer. The control of the direct feeding of the statesby gating on the Total Kinetic Energy Loss, together with the unique capabilities of the two spectrometers, was crucial for the measurementin 108Sn.

Transfer reactions have always been of great importance for nuclear structure and reaction mechanism studies. So far, in multinucleon transfer studies, proton pickup channels have been completely identified in atomic and mass numbers at energies close to the Coulomb barrier only in few cases. We measured the multinucleon transfer reactions in the 40Ar+208Pb system near the Coulomb barrier, by employing the PRISMA magnetic spectrometer. By using the most neutron-rich stable 40Ar beam we could populate, besidesneutron pickup and proton stripping channels, also neutron stripping and proton pickup channels. Comparison ofcross sections between different systems with the 208Pb target and with projectiles going from neutron-poor to neutron-rich nuclei, as well as between the data and GRAZING calculations, was carried out.Finally, recent results concerning the measurement of the excitation function from the Coulomb barrier to far below for the 92Mo+54Fe system, where both proton stripping and pickup channels were populated with similar strength, will be discussed.

58Ni +64Ni is the first case where the influence of positive Q-value transfer channels on sub-barrier fusion was evidenced, in a very well known experiment by Beckerman et al., by comparing with the two systems 58Ni + 58Ni and 64Ni+64Ni. Subsequent measurements on 64Ni + 64Ni showed that fusion hindrance is clearly present in this case. On the other hand, no indication of hindrance can be observed for 58Ni + 64Ni down to the measured level of 0.1 mb. In the present experiment the excitation function has been extended by two orders of magnitude downward. The cross sections for 58Ni + 64Ni continue decreasing very smoothly below the barrier, down to '1 µb. The logarithmic slope of the excitation function increases slowly, showing a tendency to saturate at the lowest energies. No maximum of the astrophysical S -factor is observed. Coupled-channels (CC) calculations using a Woods-Saxon potential and includinginelastic excitations only, underestimate the sub-barrier cross sections by a large amount. Good agreement is found by adding two-neutron transfer couplings to a schematical level. This behaviour is quite different from what already observed for 64Ni+ 64Ni (no positive Q-value transfer channels available), where a clear low-energy maximum of the S -factorappears, and whose excitation function is overestimated by a standard Woods-Saxon CC calculation. No hindrance effect is observed in 58Ni+ 64Ni in the measured energy range. This trend at deep sub-barrier energies reinforces the recent suggestion that the availability of several states following transfer with Q>0, effectively counterbalances the Pauli repulsion that, in general, is predicted to reduce tunneling probability inside the Coulomb barrier.

The mercury isotopic chain is depicted as one of the best fields to observe many phenomena related to collectivity evolution as, for instance, shape transition, shape coexistence or shape staggering. In this context, the 189Hg presents several interesting aspects and is still relatively unexplored. The nucleus has been studied at the Laboratori Nazionali di Legnaro using a fusion-evaporation reaction and the γ rays emitted have been detected by the GALILEO array, coupled with Neutron Wall and the GALILEO plunger. The presorting and the preliminary results are presented.

Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) tissue pathology study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository., Methods: RECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Causal inference methods will be employed to investigate associations between risk factors and pathologic outcomes., Discussion: RECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Brendan Parent reports receiving a research gift from United Therapeutics. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Troxel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The distal radial artery has emerged as an alternative vascular-access site to conventional transfemoral and transradial approaches. The main advantage over the conventional transradial route is the reduced risk of radial artery occlusion, especially in those patients who, for various clinical reasons, have to undergo repeated endovascular procedures. This study aims to assess the efficacy and safety of distal radial access for transcatheter arterial chemoembolization of the liver., Methods: This investigation is a single-center retrospective analysis of 42 consecutive patients who had undergone, from January 2018 to December 2022, transcatheter arterial chemoembolization of the liver with distal radial access for intermediate-stage hepatocellular carcinoma. Outcome data were compared with a retrospectively constituted control group of 40 patients undergoing drug-eluting beads-transcatheter arterial chemoembolization with femoral access., Results: Technical success was achieved in all cases, with a 2.4% conversion rate for distal radial access. A superselective chemoembolization was performed in 35 (83.3%) cases of distal radial access. No episode of radial artery spasm or radial artery occlusion occurred. No significant differences in efficacy and safety were observed between the distal radial access group and the femoral access group., Conclusions: Distal radial access is effective, safe, and comparable to femoral access in patients undergoing transcatheter arterial chemoembolization of the liver.

TACE plays a pivotal role in hepatocellular carcinoma, from disease control to downstaging and bridging to liver transplant. Response to TACE is a surrogate marker of tumor aggressive biology, with manifold practical implications such as survival, the need for more aggressive treatments in the intermediate stage, the selection of patients on the transplant waiting list, the dropout rate from the transplant list and the post-transplant recurrence rate. Inflammation-based scores are biomarkers of the relationship between the tumor stromal microenvironment and the immune response. Investigating the connection among the tumor stromal microenvironment, biomarkers, and the response to TACE is crucial to recognize TACE refractoriness/failure, thus providing patients with tailored therapeutics. This review aims to provide a comprehensive overview of the prognostic roles of the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), the platelet-to-lymphocyte ratio (PLR), and the lymphocyte-to-C reactive protein ratio (LCR) in patients with HCC undergoing chemoembolization of the liver. Inflammation-based scores may be convenient, easily obtained, low-cost, and reliable biomarkers with prognostic significance for HCC undergoing TACE. Baseline cut-off values differ between various studies, thus increasing confusion about using of inflammation-based scores in clinical practice. Further investigations should be conducted to establish the optimal cut-off values for inflammation-based scores, consolidating their use in clinical practice.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy burdened by poor prognosis. While huge progress of immunotherapy has recently improved the outcome of B-cell malignancies, the lack of tumor-restricted T-cell antigens still hampers its progress in T-ALL. Therefore, innovative immunotherapeutic agents are eagerly awaited. To this end, we generated a novel asymmetric (2 + 1) bispecific T-cell engager (BTCE) targeting CD1a and CD3ε (CD1a x CD3ε) starting from the development of a novel mAb named UMG2. UMG2 mAb reacts against CD1a, a glycoprotein highly expressed by cortical T-ALL cells. Importantly, no UMG2 binding was found on normal T-cells. CD1a x CD3ε induced high T-cell mediated cytotoxicity against CD1a+ T-ALL cells in vitro, as demonstrated by the concentration-dependent increase of T-cell proliferation, degranulation, induction of cell surface activation markers, and secretion of pro-inflammatory cytokines. Most importantly, in a PBMC-reconstituted NGS mouse model bearing human T-ALL, CD1a x CD3ε significantly inhibited the growth of human T-ALL xenografts, translating into a significant survival advantage of treated animals. In conclusion, CD1a x CD3ε is a novel BTCE highly active against CD1a-expressing cortical-derived T-ALL cells suitable for clinical development as an effective therapeutic option for this rare and aggressive disease.

Background: Frontline immune checkpoint inhibitors (ICI)-based regimens in non-oncogene-addicted non-small-cell lung cancer (NSCLC) have been deeply investigated. To rank the available therapeutic options, we carried out a systematic review and Bayesian meta-analysis., Methods: A comprehensive search for randomized controlled trials (RCTs) of ICI regimens, and a pairwise and a network meta-analysis (NMA) with an all-comers and a stratified strategy were conducted. Endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (TRAEs)., Results: Nineteen RCTs involving 17 treatment regimens were included. For the all-comers population, pembrolizumab/chemotherapy (CT) and cemiplimab were most likely the best treatments. For programmed death-ligand 1 (PD-L1) <1% nivolumab/ipilimumab with/without CT, for PD-L1 >1% and 1%-49% pembrolizumab/CT and for PD-L1 >50% cemiplimab ranked first for OS. In non-squamous (NSQ), pembrolizumab with/without CT ranked first for OS; cemiplimab ranked worse than the unselected population. In squamous (SQ), pooled hazard ratio (HR) showed a better chance in improving efficacy for combination strategy, while monotherapy did not, except for cemiplimab that ranked second. Atezolizumab/CT/bevacizumab ranked first in most subgroups for PFS. Direct comparison showed a non-statistically significant benefit of ICI regimens for the liver metastases cohort in OS, with a good ranking for pembrolizumab/CT and atezolizumab/bevacizumab/CT. Regarding brain metastases, all ICI regimens demonstrated an improvement in OS and PFS compared to CT. Nivolumab/ipilimumab/CT ranked better in this subset., Conclusions: Our meta-analysis updated on the most recent findings demonstrates that different ICI treatments rank differently in specific NSCLC settings (histology, biomarker and clinical presentation) offering a novel challenging scenario for clinical decision making and research planning., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Among deregulated microRNAs (miRs) in human malignancies, miR-221 has been widely investigated for its oncogenic role and as a promising biomarker. Moreover, recent evidence suggests miR-221 as a fine-tuner of chronic liver injury and inflammation-related events. Available information also supports the potential of miR-221 silencing as promising therapeutic intervention. In this systematic review, we selected papers from the principal databases (PubMed, MedLine, Medscape, ASCO, ESMO) between January 2012 and December 2020, using the keywords "miR-221" and the specific keywords related to the most important hematologic and solid malignancies, and some non-malignant diseases, to define and characterize deregulated miR-221 as a valuable therapeutic target in the modern vision of molecular medicine. We found a major role of miR-221 in this view., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Immune checkpoint inhibitors (ICIs) represent an important advance in the adjuvant treatment of patients with high-risk melanoma. Although the safety profile of anti-programmed cell death protein-1 (PD-1) is fairly acceptable, different immune-related adverse events (irAEs) are described. Herein we report for the first time a notably multidisciplinary combined approach on a malignant melanoma (MM) patient treated with anti-PD-1 antibody in adjuvant setting. In this novel approach, corticosteroid-refractory immune-mediated colitis (IMC) was effectively treated with Vedolizumab, a selective blockade of the α4β7 integrin and corticosteroids were successfully administered for autoimmune neutropenia. Notably, our patient also express HLA-B*35, a potential biomarker for predicting a genetic basis of autoimmune susceptibility. Our experience offers a possible future perspective about the use of Vedolizumab together with immunotherapy in a strategic early approach for high-risk patients genotyped for HLA., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

In patients with early-stage hepatocellular carcinoma, awaiting liver transplantation, current guidelines by AASLD and ESMO recommend a bridging therapy with a loco-regional treatment to prevent progression outside transplantation criteria. The standard of care in delaying disease progression has been recognized to be the transarterial chemoembolization. Permanent occlusion of tumor feeding vessels has effects on tumour stromal microenvironment by inducing intra- and intercellular signaling processes counteracting hypoxia, such as the release of vascular endothelial growth factor, a promoter of neoangiogenesis, tumour proliferation and metastatic growth. Among chemoembolization interventions, TACE with degradable starch microspheres represents an alternative to conventional cTACE and DEB-TACE and it minimizes detrimental effects on tumour stromal microenvironment, guaranteeing a transient occlusion of tumour feeding arteries and avoiding VEGF overexpression.Between January 2015 and September 2020, 54 consecutive patients with early-stage hepatocellular carcinoma and Child-Pugh stage B, who had undergone DSM-TACE as a bridging therapy while awaiting liver transplantation, were eligible for the study. A total of 154 DSM-TACE was performed, with a mean number of 2.85 procedures per patient. 18 patients (33.3%) succeeded in achieving liver transplantation, with a mean waiting time-to-transplantation of 11.7 months. The cumulative rates of patients still active on the WL at 6 months were about 91 and 93% when considering overall drop-out and tumour-specific drop-out respectively. Overall survival was about 96% at 6 months and 92% at 12 months. 17 patients experienced adverse events after the chemoembolizations. For patients with HCC in the transplant waiting list and within the Child-Pugh B stage, life expectancy may be dominated by the liver dysfunction, rather than by the tumour progression itself. In this population subset, the choice of LRT is critical because LRT itself could become a dangerous tool that is likely to precipitate liver dysfunction to an extent that survival is shortened rather than prolonged. Hence, the current study demonstrates that DSM-TACE is not far from being an ideal LRT, because it has an excellent safety profile, maintaining an efficacy that guarantees a clear advantage on the dropout rate with respect to the non-operative strategy, thus justifying its use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer VB declared a past co-authorship with one of the authors MAS to the handling editor., (Copyright © 2021 Minici, Ammendola, Manti, Siciliano, Giglio, Minici, Melina, Currò and Laganà.)

According to the EASL Guidelines for the management of hepatocellular carcinoma, transcatheter arterial chemoembolization is the first-line treatment recommended for intermediate-stage HCC. Furthermore, it is widely accepted that patients beyond the Milan criteria can be considered for a liver transplant after successful downstaging to within the Milan criteria. Response to downstaging treatments significantly influences not just drop-outs, but also the rate of post-transplantation tumor recurrences. TACE with degradable starch microspheres represents an alternative to conventional TACE with lipiodol and TACE with drug-eluting beads, and it leads to transient arterial occlusion allowing lower activation of hypoxia-inducible factors and less release of vascular endothelial growth factor, a promoter of neoangiogenesis, tumor proliferation, and metastatic growth. In patients with intermediate-stage HCC and a Child-Pugh score of 8 or 9, life expectancy may be dominated by cirrhotic liver dysfunction, rather than by the tumor progression itself; hence, locoregional treatments might also be detrimental, precipitating liver dysfunction to an extent that survival is shortened rather than prolonged. Data on tolerability, toxicity, and effectiveness of DSM-TACE are limited but encouraging. Between January 2015 and October 2020, 50 consecutive patients with intermediate-stage hepatocellular carcinoma and a Child-Pugh score of 8/9, who had undergone DSM-TACE as the first-line treatment, were eligible for the study. A total of 142 DSM-TACEs were performed, with a mean number of 2.84 procedures per patient. The mean time-to-downstaging was 19.2 months, with six patients successfully downstaged. OS was about 100% at six months, 81.8% at 12 months, and 50% at 24 months. Twenty-two patients experienced adverse events after chemoembolization. The median OS and safety of DSM-TACE in this study are comparable with other published investigations in this field. Furthermore, 12% of patients were successfully downstaged. Hence, the results of the current investigation demonstrate that DSM-TACE is effective and safe in intermediate-stage HCC, achieving an interesting downstaging rate. Such data were observed in the population subset with a Child-Pugh score of 8 or 9, in which life expectancy may be determined by cirrhotic liver dysfunction, so the achievement of a balance between the safety and efficacy profile of the TACE treatment is crucial., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Minici, Ammendola, Manti, Siciliano, Minici, Komaei, Currò and Laganà.)

Background: Immune checkpoint inhibitors targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death-1 receptor (PD-1), and programmed death-1 receptor and its ligand (PD-L1) increased the survival of patients affected by metastatic malignant melanoma. Due to their mechanism of action, these drugs are associated with a unique toxicity profile. Indeed, immune-related adverse events (irAEs) present a wide clinical spectrum representing the Achilles' heel of immunotherapy. Overall, cutaneous toxicities are among the most common irAEs. Immunomodulatory drugs are used for the management of irAEs and can theoretically lead to tumor escape., Case Presentation: We report the case of a 75-year-old man with metastatic melanoma receiving the anti-PD1 Pembrolizumab therapy. After 10 treatment cycles, the patient came to our clinic with itchy psoriatic manifestations widespread >30% of the body surface [12.3 Psoriasis Area and Severity Index (PASI) score] that negatively impacted on the patient's quality of life and compliance with immunotherapy. Additionally, he had no positive personal history of psoriasis. Given the severity of the cutaneous manifestations, in a multidisciplinary approach, Apremilast (an oral small molecule PDE4 inhibitor) was started. Furthermore, Pembrolizumab was interrupted for 4 weeks until the improvement of skin lesions and the disappearance of itching. Immunosuppressive methylprednisolone therapy was initiated with a dose of 16 mg/die; then, this initial dose was progressively reduced until discontinuation. After 10 months, the patient had a good general clinical condition with psoriasis complete remission. Moreover, positron emission tomography (PET) and computed tomography (CT) scans showed complete response by immune Response Evaluation Criteria in Solid Tumors (iRECIST)., Conclusion: To the best of our knowledge, this is the first report on the safety and efficacy of Apremilast for the treatment of immunotherapy-induced psoriasis in metastatic melanoma., (Copyright © 2020 Siciliano, Dastoli, d’Apolito, Staropoli, Tassone, Tagliaferri and Barbieri.)