First application of mass measurement with the Rare-RI Ring reveals the solar r-process abundance trend at A=122 and A=123

The Rare-RI Ring (R3) is a recently commissioned cyclotron-like storage ring mass spectrometer dedicated to mass measurements of exotic nuclei far from stability at Radioactive Isotope Beam Factory (RIBF) in RIKEN. The first application of mass measurement using the R3 mass spectrometer at RIBF is reported. Rare isotopes produced at RIBF, $^{127}$Sn, $^{126}$In, $^{125}$Cd, $^{124}$Ag, $^{123}$Pd, were injected in R3. Masses of $^{126}$In, $^{125}$Cd, and $^{123}$Pd were measured whereby the mass uncertainty of $^{123}$Pd was improved. This is the first reported measurement with a new storage ring mass spectrometery technique realized at a heavy-ion cyclotron and employing individual injection of the pre-identified rare nuclei. The latter is essential for the future mass measurements of the rarest isotopes produced at RIBF. The impact of the new $^{123}$Pd result on the solar $r$-process abundances in a neutron star merger event is investigated by performing reaction network calculations of 20 trajectories with varying electron fraction $Y_e$. It is found that the neutron capture cross section on $^{123}$Pd increases by a factor of 2.2 and $\beta$-delayed neutron emission probability, $P_\mathrm{1n}$, of $^{123}$Rh increases by 14\%. The neutron capture cross section on $^{122}$Pd decreases by a factor of 2.6 leading to pileup of material at $A=122$, thus reproducing the trend of the solar $r$-process abundances. The trend of the two-neutron separation energies (S$_\mathrm{2n}$) was investigated for the Pd isotopic chain. The new mass measurement with improved uncertainty excludes large changes of the S$_\mathrm{2n}$ value at $N=77$. Such large increase of the S$_\mathrm{2n}$ values before $N=82$ was proposed as an alternative to the quenching of the $N=82$ shell gap to reproduce $r$-process abundances in the mass region of $A=112-124$

Oncolytic Adenoviruses in Gastrointestinal Cancers

Gastrointestinal malignancies are challenging cancers with considerable economic and societal impacts on health care systems worldwide. While advances in surgical approaches have provided benefits to a proportion of patients, only modest improvements have been attained in the treatment of patients with advanced disease, resulting in limited improvement in survival rates in these patients. Oncolytic adenoviruses are being developed to address gastrointestinal malignancies. Each platform has evolved to maximize tumor-cell killing potency while minimizing toxicities. Tumor-specific bioengineered adenoviruses using chimeric promoters, prodrug convertase enzymes, lethal genes, tumor suppressor genes, and pseudo-typed capsids can provide the innovations for eventual success of oncolytic virotherapy. This article will review the developments in adenoviral platforms in the context of specific gastrointestinal cancers. From the bench to the implementation of clinical trials, this review aims to highlight advances in the field from its early days to the current state of affairs as it pertains to the application of adenoviral oncolytic therapy to gastrointestinal cancers

P16 immunohistochemistry is a sensitive and specific surrogate marker for CDKN2A homozygous deletion in gliomas

Abstract Molecular characterization of gliomas has uncovered genomic signatures with significant impact on tumor diagnosis and prognostication. CDKN2A is a tumor suppressor gene involved in cell cycle control. Homozygous deletion of the CDKN2A/B locus has been implicated in both gliomagenesis and tumor progression through dysregulated cell proliferation. In histologically lower grade gliomas, CDKN2A homozygous deletion is associated with more aggressive clinical course and is a molecular marker of grade 4 status in the 2021 WHO diagnostic system. Despite its prognostic utility, molecular analysis for CDKN2A deletion remains time consuming, expensive, and is not widely available. This study assessed whether semi-quantitative immunohistochemistry for expression of p16, the protein product of CDKN2A, can serve as a sensitive and a specific marker for CDKN2A homozygous deletion in gliomas. P16 expression was quantified by immunohistochemistry in 100 gliomas, representing both IDH-wildtype and IDH-mutant tumors of all grades, using two independent pathologists’ scores and QuPath digital pathology analysis. Molecular CDKN2A status was determined using next-generation DNA sequencing, with homozygous CDKN2A deletion detected in 48% of the tumor cohort. Classifying CDKN2A status based on p16 tumor cell expression (0–100%) demonstrated robust performance over a wide range of thresholds, with receiver operating characteristic curve area of 0.993 and 0.997 (blinded and unblinded pathologist p16 scores, respectively) and 0.969 (QuPath p16 score). Importantly, in tumors with pathologist-scored p16 equal to or less than 5%, the specificity for predicting CDKN2A homozygous deletion was 100%; and in tumors with p16 greater than 20%, specificity for excluding CDKN2A homozygous deletion was also 100%. Conversely, tumors with p16 scores of 6–20% represented gray zone with imperfect correlation to CDKN2A status. The findings indicate that p16 immunohistochemistry is a reliable surrogate marker of CDKN2A homozygous deletion in gliomas, with recommended p16 cutoff scores of ≤ 5% for confirming and > 20% for excluding biallelic CDKN2A loss