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The 26Al abundance holds a special role in present-day astrophysics, since it is a probe of active nucleosynthesis in the Galaxy and a valuable constraint of Galactic core-collapse supernovae rate. It is estimated through the detection of the 1809-keV γ-line of the daughter 26Mg and from the superabundance of 26Mg in comparison with the most abundant 24Mg isotope in meteorites. Accurate knowledge of the reaction rates involving 26Al, its stable counterpart 27Al and 24Mg is then mandatory. Moreover, these nuclei enter the MgAl cycle playing an important role in the production of Al and Mg isotopes. Recently, high-resolution stellar surveys have shown that the Mg-Al anti-correlation in red giants of globular clusters may hide the existence of multiple stellar populations, and that the relative abundances of Mg isotopes may not show correlation with Al.The common thread running through these astrophysical scenarios is the 27Al(p,α)24Mg reaction, which is the main 27Al destruction channel and directly correlates its abundance with the 24Mg one. Since available reaction rates show an order of magnitude uncertainty owing to the vanishingly small cross section at astrophysical energies, we have applied the Trojan Horse Method to deduce the reaction rate with no need of extrapolation. The indirect measurement made it possible to assess the contribution of the 84-keV resonance and to lower the upper limits on the strength of nearby resonances, with potential important impact for astrophysics. In particular, modifications in the 27Al and 24Mg abundances up to ∼30% are predicted for intermediate mass stars.

Background: Epidermal growth factor receptor (EGFR) mutation testing is recommended in metastatic non-small cell lung cancer (NSCLC). The objective of this study was to assess changes in EGFR mutation testing patterns and tyrosine kinase inhibitor (TKI) use in US veterans with stage III-IV NSCLC between 2013 and 2017. Patients and Methods: Retrospective study using linked data from Department of Veterans Affairs (VA) Cancer Registry System, Corporate Data Warehouse, commercial laboratories, and clinical notes. Generalized linear mixed models accounting for clustering by VA facility were used to determine factors associated with EGFR mutation testing. Results: From 2013 to 2017, EGFR mutation testing increased from 29.5% to 38.4% among veterans with stage III-IV NSCLC and from 47.0% to 57.4% among veterans with stage IV non-squamous disease. Factors associated with increased odds of testing included being married, Medicare enrollment, and adenocarcinoma histology. Factors associated with decreased odds of testing included Medicaid eligibility, stage III disease, increasing age, being a current or former smoker, increasing Charlson-Deyo comorbidity score, and receiving cancer care in the South. Appropriate use of a TKI rose from 2013 to 2017 (17.2% to 74.1%). Conclusion: EGFR mutation testing rates increased to almost 60% in the stage IV non-squamous NSCLC population in 2017, with residual opportunity for further increase. Several sociodemographic characteristics, comorbidities, and geographic regions were associated with EGFR mutation testing suggestive of inequitable testing decisions. Appropriate use of TKI improved drastically from 2013 to 2017 demonstrating rapidly changing practice patterns through the adoption phase of new treatment options.

High energy gamma-rays from the 116Sn + 24Mg reaction at 23A MeV were measured using the MEDEA detector at LNS – INFN Catania. Combining this new data with previous measurements yields a detailed view of the quenching of the Giant Dipole Resonance as a function of excitation energy in nuclei of mass A in the range 120÷132. The transition towards the disappearance of the dipole strength, which occurs around 230 MeV excitation energy, appears to be remarkably sharp. Current phenomenological models give qualitative explanations for the quenching but cannot reproduce its detailed features. Keywords: Giant Dipole Resonance, Hot nuclei, Fusion reactions, Statistical Model

The fragmentation of quasi-projectiles from the nuclear reaction 40Ca+12C at 25 MeV per nucleon bombarding energy was used to produce α-emission sources. From a careful selection of these sources provided by a complete detection and from comparisons with models of sequential and simultaneous decays, evidence in favor of α-particle clustering from excited 16O, 20Ne and 24Mg is reported. Keywords: Heavy ion reactions, alpha-particle clustering, alpha-conjugate nuclei, Cluster models

Large-vessel vasculitides (LVV) comprise a group of chronic inflammatory diseases of the aorta and its major branches. The most common forms of LVV are giant cell arteritis (GCA) and Takayasu arteritis (TAK). Both GCA and TAK are characterized by granulomatous inflammation of the vessel wall accompanied by a maladaptive immune and vascular response that promotes vascular damage and remodeling. The inflammatory process in LVV starts in the adventitia where fibroblasts constitute the dominant cell population. Fibroblasts are traditionally recognized for synthesizing and renewing the extracellular matrix thereby being major players in maintenance of normal tissue architecture and in tissue repair. More recently, fibroblasts have emerged as a highly plastic cell population exerting various functions, including the regulation of local immune processes and organization of immune cells at the site of inflammation through production of cytokines, chemokines and growth factors as well as cell-cell interaction. In this review, we summarize and discuss the current knowledge on fibroblasts in LVV. Furthermore, we identify key questions that need to be addressed to fully understand the role of fibroblasts in the pathogenesis of LVV., Competing Interests: Declaration of competing interest Kornelis S.M. van der Geest received speaking fee from Roche, and research support from AbbVie and Siemens Healthineers. Other authors had no conflicts of interest to declare. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Kornelis S.M. van der Geest reports a relationship with Roche that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Clinical practice suggests that rheumatic heart disease (RHD) represents a significant public health challenge in the Caribbean region where advanced disease appears early often leading to surgical intervention. We aimed to determine the burden of RHD and type of procedure among patients undergoing valve surgery in the Dominican Republic (DR)., Methods: Demographic, clinical and procedural data of all subjects intervened between January 2014 and December 2018 were obtained including valve disorder, anatomic location and type of surgery. Correlation coefficients were used to assess yearly trends of RHD among the 7 cardiovascular surgical centers in the country., Results: Of 1626 valvular surgeries performed, 733 (45%) corresponded to RHD; 55% female patients, age 50 ± 11 (6-72) years; involving mitral 458 (63%); mitral + aortic 139 (19%); aortic 105 (14%); mitral + tricuspid 31 (4%); 95% prosthetic replacement and 5% mitral/tricuspid repairs. Mean proportion of RHD valve procedures per center for the study period was 53 ± 34%. Age-adjusted analysis showed an overall upwards trend in RHD valvular surgery (mean annual increment of 50 ± 40%, P = 0.01)., Conclusions: Despite inter-center variability, rates of surgical RHD in the DR increased during the last 5 years affecting a relatively young population. Mitral involvement was the predominant lesion and prosthetic replacement the leading procedure. These data may guide local and regional institutions and policy makers towards the implementation of cost-effective initiatives against RHD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A major limitation for adenoviral transduction in vivo is the profound liver tropism of adenovirus type 5 (Ad5). Recently, we demonstrated that coagulation factor X (FX) binds to Ad5-hexon protein at high affinity to mediate hepatocyte transduction after intravascular delivery. We developed novel genetically FX-binding ablated Ad5 vectors with lower liver transduction. Here, we demonstrate that FX-binding ablated Ad5 predominantly localize to the liver and spleen 1 hour after injection; however, they had highly reduced liver transduction in both control and macrophage-depleted mice compared with Ad5. At high doses in macrophage-depleted mice, FX-binding ablated vectors transduced the spleen more efficiently than Ad5. Immunohistochemical studies demonstrated transgene colocalization with CD11c(+), ER-TR7(+), and MAdCAM-1(+) cells in the splenic marginal zone. Systemic inflammatory profiles were broadly similar between FX-binding ablated Ad5 and Ad5 at low and intermediate doses, although higher levels of several inflammatory proteins were observed at the highest dose of FX-binding ablated Ad5. Subsequently, we generated a FX-binding ablated virus containing a high affinity Ad35 fiber that mediated a significant improvement in lung/liver ratio in macrophage-depleted CD46(+) mice compared with controls. Therefore, this study documents the biodistribution and reports the retargeting capacity of FX binding-ablated Ad5 vectors in vitro and in vivo.

Recent studies have demonstrated the importance of coagulation factor X (FX) in adenovirus (Ad) serotype 5-mediated liver transduction in vivo. FX binds to the adenovirus hexon hypervariable regions (HVRs). Here, we perform a systematic analysis of FX binding to Ad5 HVRs 5 and 7, identifying domains and amino acids critical for this interaction. We constructed a model of the Ad5-FX interaction using crystallographic and cryo-electron microscopic data to identify contact points. Exchanging Ad5 HVR5 or HVR7 from Ad5 to Ad26 (which does not bind FX) diminished FX binding as analyzed by surface plasmon resonance, gene delivery in vitro, and liver transduction in vivo. Exchanging Ad5-HVR5 for Ad26-HVR5 produced deficient virus maturation. Importantly, defined mutagenesis of just 2 amino acids in Ad5-HVR5 circumvented this and was sufficient to block liver gene transfer. In addition, mutation of 4 amino acids in Ad5-HVR7 or a single mutation at position 451 also blocked FX-mediated effects in vitro and in vivo. We therefore define the regions and amino acids on the Ad5 hexon that bind with high affinity to FX thereby better defining adenovirus infectivity pathways. These vectors may be useful for gene therapy applications where evasion of liver transduction is a prerequisite.

We evaluated the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in 78 Italian patients with hereditary hemochromatosis as well as the relation between HCV antibody (anti-HCV) status, hepatitis B surface antigen (HBsAg) and liver histology. None of the patients had been transfused or ever consumed more than 60 g of alcohol per day. Eighteen showed histological signs of chronic hepatitis, active cirrhosis was present in 12, chronic active hepatitis in 4 and chronic persistent hepatitis in 2. Liver fibrosis or cirrhosis without inflammatory activity was observed in 31 subjects, whereas liver histology was normal except for iron overload in 18. The prevalence of HBsAg in the whole series was 5% and of anti-HCV was 20.5%. The prevalence of HBsAg and anti-HCV was significantly higher in the chronic hepatitis group than in the fibrosis/cirrhosis (p = 0.01) and the normal groups (p < 0.01). Fourteen of 18 hereditary hemochromatosis patients with chronic hepatitis were HBsAg (4) or anti-HCV (10) positive and all the latter subgroup had HCV-RNA in their serum as shown by the polymerase chain reaction. Although most of the patients with associated chronic hepatitis had cirrhosis, their serum ferritin levels and amount of mobilizable iron were significantly lower than those of the fibrosis/cirrhosis group (p < 0.01). This indicates that hepatitis viral infection acts synergistically with iron in accelerating the development of liver damage.