Adjuvant PD-1 and PD-L1 Inhibitors and Relapse-Free Survival in Cancer Patients: The MOUSEION-04 Study

Background: Adjuvant treatment has always been a cornerstone in the therapeutic approach of many cancers, considering its role in reducing the risk of relapse and, in some cases, increasing overall survival. Adjuvant immune checkpoint inhibitors have been tested in different malignancies. Methods: We performed a meta-analysis aimed to explore the impact of adjuvant PD-1 and PD-L1 inhibitors on relapse-free survival (RFS) in cancer patients enrolled in randomized controlled clinical trials. We retrieved all phase III trials published from 15 June 2008 to 15 May 2022, evaluating PD-1/PD-L1 inhibitors monotherapy as an adjuvant treatment by searching on EMBASE, Cochrane Library, and PubMed/ Medline, and international oncological meetings’ abstracts. The outcome of interest was RFS. We also performed subgroup analyses focused on age and gender. Results: Overall, 8 studies, involving more than 6000 patients, were included in the analysis. The pooled results highlighted that the use of adjuvant PD-1/PD-L1 inhibitors may reduce the risk of relapse compared to control treatments (hazard ratio, 0.72; 95% confidence intervals, 0.67–0.78). In addition, the subgroup analyses observed that this benefit was consistent in different patient populations, including male, female, younger, and older patients. Conclusions: Adjuvant anti-PD-1/PD-L1 treatment is associated with an increased RFS in the overall population and in subgroups divided according to age and gender

Structural, 57 Fe Mössbauer and XPS studies of mechanosynthesized nanocrystalline Nd0.33Eu0.67Fe1-xCrxO3 particles

We report on the structure and surface composition of Nd0.33Eu0.67Fe1-xCrxO3 (x = 0.0, 0.3, 0.5, 0.7, 0.9 and 1.0) nanoparticles (∼30 nm) mechanosynthesized at temperatures that are ∼ 470– 700 °C lower than those at which the pure and doped pristine materials conventionally form. XRD Rietveld and FT-IR analyses show that with increasing x the lattice parameters decrease and the bond lengths and angles vary in a way that reduces crystalline distortion. Whilst the majority of the Eu3+/Nd3+ and Fe3+/Cr3+ cations occupy the normal perovskite-related A- and B-sites, respectively, ∼ 5% of them exchange sites. 57Fe Mössbauer spectroscopy confirms the presence of these antisites and reveals a superparamagnetic behaviour at 298 K that enhances with increasing x. XPS measurement reveals a complex surface composition of the nanoparticles with traces of Eu2O3, Nd2O3, Cr2O3 and Fe2O3 as well as partial O2--deficiency

The Light Stop Scenario from Gauge Mediation

In this paper we embed the light stop scenario, a MSSM framework which explains the baryon asymmetry of the universe through a strong first order electroweak phase transition, in a top-down approach. The required low energy spectrum consists in the light SM-like Higgs, the right-handed stop, the gauginos and the Higgsinos while the remaining scalars are heavy. This spectrum is naturally driven by renormalization group evolution starting from a heavy scalar spectrum at high energies. The latter is obtained through a supersymmetry-breaking mix of gauge mediation, which provides the scalars masses by new gauge interactions, and gravity mediation, which generates gaugino and Higgsino masses. This supersymmetry breaking also explains the \mu\ and B_\mu\ parameters necessary for electroweak breaking and predicts small tri-linear mixing terms A_t in agreement with electroweak baryogenesis requirements. The minimal embedding predicts a Higgs mass around its experimental lower bound and by a small extension higher masses m_H\lesssim 127 GeV can be accommodated.Comment: 20 pages, 3 figures; v2: changes in the conventions; v3: more details on the Higgs mass prediction, version published in JHE

Lattice gauge theory with baryons at strong coupling

We study the effective Hamiltonian for strong-coupling lattice QCD in the case of non-zero baryon density. In leading order the effective Hamiltonian is a generalized antiferromagnet. For naive fermions, the symmetry is U(4N_f) and the spins belong to a representation that depends on the local baryon number. Next-nearest-neighbor (nnn) terms in the Hamiltonian break the symmetry to U(N_f) x U(N_f). We transform the quantum problem to a Euclidean sigma model which we analyze in a 1/N_c expansion. In the vacuum sector we recover spontaneous breaking of chiral symmetry for the nearest-neighbor and nnn theories. For non-zero baryon density we study the nearest-neighbor theory only, and show that the pattern of spontaneous symmetry breaking depends on the baryon density.Comment: 31 pages, 5 EPS figures. Corrected Eq. (6.1

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

High Temperature Phase Transition in Two-Scalar Theories

Two-scalar theories at high temperature exhibit a rich spectrum of possible critical behaviour, with a second or first order phase transition. In the vicinity of the critical temperature one can observe critical exponents, tricritical points and crossover behaviour. None of these phenomena are visible to high temperature perturbation theory.Comment: 39 pages, macro equation.sty included, 11 uuencoded figures

2015年にミャンマー国で発生したデング熱流行の臨床、ウイルス学、疫学解析

Hospital-based surveillance was conducted at two widely separated regions in Myanmar during the 2015 dengue epidemic. Acute phase serum samples were collected from 332 clinically diagnosed dengue patients during the peak season of dengue cases. Viremia levels were measured by quantitative real-time PCR and plaque assays using FcγRIIA-expressing and non-FcγRIIA-expressing BHK cells to specifically determine the infectious virus particles. By serology and molecular techniques, 280/332 (84・3%) were confirmed as dengue patients. All four serotypes of dengue virus (DENV) were isolated from among 104 laboratory-confirmed patients including two cases infected with two DENV serotypes. High percentage of primary infection was noted among the severe dengue patients. Patients with primary infection or DENV IgM negative demonstrated significantly higher viral loads but there was no significant difference among the severity groups. Viremia levels among dengue patients were notably high for a long period which was assumed to support the spread of the virus by the mosquito vector during epidemic. Phylogenetic analyses of the envelope gene of the epidemic strains revealed close similarity with the strains previously isolated in Myanmar and neighboring countries. DENV-1 dominated the epidemic in 2015 and the serotype (except DENV-3) and genotype distributions were similar in both study sites.長崎大学学位論文 学位記番号:博(医歯薬)甲第984号 学位授与年月日:平成29年9月20日Author: A. K. KYAW, M. M. NGWE TUN, M. L. MOI, T. NABESHIMA, K. T. SOE, S. M. THWE, A. A. MYINT, K. T. T. MAUNG, W. AUNG, D. HAYASAKA, C. C. BUERANO, K. Z. THANT and K. MORITACitation: Epidemiology & Infection, 145(9), pp.1886-1897; 2017Nagasaki University (長崎大学)課程博

Activation of Type I and III Interferon Signalling Pathways Occurs in Lung Epithelial Cells Infected with Low Pathogenic Avian Influenza Viruses

The host response to the low pathogenic avian influenza (LPAI) H5N2, H5N3 and H9N2 viruses were examined in A549, MDCK, and CEF cells using a systems-based approach. The H5N2 and H5N3 viruses replicated efficiently in A549 and MDCK cells, while the H9N2 virus replicated least efficiently in these cell types. However, all LPAI viruses exhibited similar and higher replication efficiencies in CEF cells. A comparison of the host responses of these viruses and the H1N1/WSN virus and low passage pH1N1 clinical isolates was performed in A549 cells. The H9N2 and H5N2 virus subtypes exhibited a robust induction of Type I and Type III interferon (IFN) expression, sustained STAT1 activation from between 3 and 6 hpi, which correlated with large increases in IFN-stimulated gene (ISG) expression by 10 hpi. In contrast, cells infected with the pH1N1 or H1N1/WSN virus showed only small increases in Type III IFN signalling, low levels of ISG expression, and down-regulated expression of the IFN type I receptor. JNK activation and increased expression of the pro-apoptotic XAF1 protein was observed in A549 cells infected with all viruses except the H1N1/WSN virus, while MAPK p38 activation was only observed in cells infected with the pH1N1 and the H5 virus subtypes. No IFN expression and low ISG expression levels were generally observed in CEF cells infected with either AIV, while increased IFN and ISG expression was observed in response to the H1N1/WSN infection. These data suggest differences in the replication characteristics and antivirus signalling responses both among the different LPAI viruses, and between these viruses and the H1N1 viruses examined. These virus-specific differences in host cell signalling highlight the importance of examining the host response to avian influenza viruses that have not been extensively adapted to mammalian tissue culture

Amplification of hypercharge electromagnetic fields by a cosmological pseudoscalar

If, in addition to the standard model fields, a new pseudoscalar field exists and couples to hypercharge topological number density, it can exponentially amplify hyperelectric and hypermagnetic fields in the symmetric phase of the electroweak plasma, while coherently rolling or oscillating. We present the equations describing the coupled system of a pseudoscalar field and hypercharge electromagnetic fields in the electroweak plasma at temperatures above the electroweak phase transition, discuss approximations to the equations, and their validity. We then solve the approximate equations using assorted analytical and numerical methods, and determine the parameters for which hypercharge electromagnetic fields can be exponentially amplified.Comment: 14 pages, 6 figure