Clinical Utility of the Combined Use of CA19-9 and DUPAN-2 in Pancreatic Adenocarcinoma.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) patients with normal carbohydrate antigen (CA) 19-9 levels can have early-stage cancer or advanced cancer without elevation of CA19-9 level; estimating their malignant potential is difficult. This study investigated the clinical utility of the combined use of preoperative CA 19-9 and Duke pancreatic monoclonal antigen type 2 (DUPAN-2) levels in patients with PDAC.

Methods: Patients who underwent curative-intent surgery for PDAC between November 2005 and December 2021 were investigated.

Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma.

Background: Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain.

Methods: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent.

Compositions and Microstructures of Carbonated Geopolymers with Different Precursors.

It is thought that geopolymers are easy to carbonate, especially when they are cured in ambient temperatures. Matrix gel's composition and microstructure, and new products of geopolymers (GPs) after carbonation were investigated in this study on the basis of XRD and SEM-EDS measurements and ternary diagram analysis, which were prepared from low-lime fly ash (FA) and ground granulated blast-furnace slag (GGBS) alone or a blend, as a precursor. The specimens were hardened in a 20 °C environment with alkali activator solution (S/N = 1.

Near-Infrared II Photobiomodulation Preconditioning Ameliorates Stroke Injury via Phosphorylation of eNOS.

Background: The current management of patients with stroke with intravenous thrombolysis and endovascular thrombectomy is effective only when it is timely performed on an appropriately selected but minor fraction of patients. The development of novel adjunctive therapy is highly desired to reduce morbidity and mortality with stroke. Since endothelial dysfunction is implicated in the pathogenesis of stroke and is featured with suppressed endothelial nitric oxide synthase (eNOS) with concomitant nitric oxide deficiency, restoring endothelial nitric oxide represents a promising approach to treating stroke injury.

Efficacy and safety of GH treatment in Japanese children with short stature due to deficiency: a randomized phase 3 study.

We conducted a randomized phase 3 study to investigate the efficacy and safety of GH treatment in prepubertal Japanese patients with short stature due to deficiency. The patients were randomly allocated to the GH-GH group (n = 10), in which the patients were treated with GH (0.35 mg/kg/wk) subcutaneously once daily for 24 mo, or the no-treatment (NT)-GH group (n = 9), in which the patients were untreated for the first 12 mo and then administered the same dosage of GH for the next 12 mo.

Functional insights of Tyr37 in framework region 2 directly contributing to the binding affinities and dissociation kinetics in single-domain VH antibodies.

Single-domain VH antibody is regarded as one of the promising antibody classes for therapeutic and diagnostic applications. VH antibodies have amino acids in framework region 2 that are distinct from those in conventional antibodies, such as the Val37Phe/Tyr (V37F/Y) substitution. Correlations between the residue type at position 37 and the conformation of the CDR3 in VH antigen recognition have been previously reported.

The Effect of Prior Creatine Intake for 28 Days on Accelerated Recovery from Exercise-Induced Muscle Damage: A Double-Blind, Randomized, Placebo-Controlled Trial.

Despite the known beneficial effects of creatine in treating exercise-induced muscle damage (EIMD), its effectiveness remains unclear. This study investigates the recovery effect of creatine monohydrate (CrM) on EIMD. Twenty healthy men (21-36 years) were subjected to stratified, randomized, double-blind assignments.

Artificial intelligence in medicine: mitigating risks and maximizing benefits via quality assurance, quality control, and acceptance testing.

The adoption of artificial intelligence (AI) tools in medicine poses challenges to existing clinical workflows. This commentary discusses the necessity of context-specific quality assurance (QA), emphasizing the need for robust QA measures with quality control (QC) procedures that encompass (1) acceptance testing (AT) before clinical use, (2) continuous QC monitoring, and (3) adequate user training. The discussion also covers essential components of AT and QA, illustrated with real-world examples.

Discovery of orbital ordering in BiSrCaCuO.

The primordial ingredient of cuprate superconductivity is the CuO unit cell. Theories usually concentrate on the intra-atom Coulombic interactions dominating the 3d and 3d configurations of each copper ion. However, if Coulombic interactions also occur between electrons of the 2p orbitals of each planar oxygen atom, spontaneous orbital ordering may split their energy levels.

Differential Pacing Maneuver From the Vein of Marshall.

Background: Bidirectional mitral isthmus (MI) block is conventionally verified by differential pacing from the coronary sinus (CS) and its sequence change. This study aimed to evaluate the ability of differential pacing from the vein of Marshall (VOM) to detect epicardial MI connections.

Methods: Radiofrequency and VOM ethanol MI ablation were performed with a VOM electrode catheter inserted to the septal side of the ablation line.

Multi-Ancestry Polygenic Risk Score for Coronary Heart Disease Based on an Ancestrally Diverse Genome-Wide Association Study and Population-Specific Optimization.

Background: Predictive performance of polygenic risk scores (PRS) varies across populations. To facilitate equitable clinical use, we developed PRS for coronary heart disease (CHD; PRS) for 5 genetic ancestry groups.

Methods: We derived ancestry-specific and multi-ancestry PRS based on pruning and thresholding (PRS) and ancestry-based continuous shrinkage priors (PRS) applied to summary statistics from the largest multi-ancestry genome-wide association study meta-analysis for CHD to date, including 1.

Intrinsic dynamic and static natures of Pn--X--Pn σ(3c-4e) type interactions (Pn = Pn = N, P, As and Sb; X = H, F, Cl, Br and I) in bicyclo[3.3.3] and bicyclo[4.4.4] systems and their behaviour, elucidated with QTAIM dual functional analysis.

The intrinsic dynamic and static natures of Pn--X--Pn (Pn = Pn: N, P, As and Sb; X = H, F, Cl, Br and I) in 1a-8c were elucidated with the quantum theory of atoms-in-molecules dual functional analysis (QTAIM-DFA). Species 1a-8c were formed by incorporating X between Pn and Pn of Pn(CHCHCH)Pn (1-4) and Pn(CHCHCHCH)Pn (5-8). The relative stabilities between the symmetric and nonsymmetric structures along with their transition states were investigated.

Fully gapped pairing state in spin-triplet superconductor UTe.

The recently discovered superconductor UTe is a promising candidate for spin-triplet superconductors, but the symmetry of the superconducting order parameter remains highly controversial. Here, we determine the superconducting gap structure by the thermal conductivity of ultraclean UTe single crystals. We find that the -axis thermal conductivity divided by temperature κ/ in zero-temperature limit is vanishingly small for both magnetic field ‖ and ‖ axes up to / ∼ 0.

J-domain proteins: From molecular mechanisms to diseases.

J-domain proteins (JDPs) are the largest family of chaperones in most organisms, but much of how they function within the network of other chaperones and protein quality control machineries is still an enigma. Here, we report on the latest findings related to JDP functions presented at a dedicated JDP workshop in Gdansk, Poland. The report does not include all (details) of what was shared and discussed at the meeting, because some of these original data have not yet been accepted for publication elsewhere or represented still preliminary observations at the time.

Inactivation of Malic Enzyme 1 in Endothelial Cells Alleviates Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is a progressive cardiopulmonary disease with a high mortality rate. Although growing evidence has revealed the importance of dysregulated energetic metabolism in the pathogenesis of PH, the underlying cellular and molecular mechanisms are not fully understood. In this study, we focused on ME1 (malic enzyme 1), a key enzyme linking glycolysis to the tricarboxylic acid cycle.

One-year outcome of brolucizumab for neovascular age-related macular degeneration in Japanese patients.

A new anti-vascular endothelial growth factor agent, brolucizumab, was approved by the United States Food and Drug Administration in 2019. We evaluated whether brolucizumab reduces the treatment burden of neovascular age-related macular degeneration (nAMD) after switching by examining 1-year treatment outcomes in a real-world setting. This retrospective single-institution study included 107 consecutive eyes with nAMD treated with brolucizumab.

Immunomodulatory effects and improved outcomes with cisplatin- versus carboplatin-based chemotherapy plus atezolizumab in urothelial cancer.

In metastatic urothelial cancer (mUC), cisplatin versus carboplatin leads to durable disease control in a subset of patients. The IMvigor130 trial reveals more favorable effects with atezolizumab combined with gemcitabine and cisplatin (GemCis) versus gemcitabine and carboplatin (GemCarbo). This study investigates the immunomodulatory effects of cisplatin as a potential explanation for these observations.

A meta-analysis and real-world cohort study on the sex-related differences in efficacy and safety of immunotherapy for hepatocellular carcinoma.

Background & Aims: Sex-related differences in the immune pathogenesis of hepatocellular carcinoma (HCC), particularly related to oestrogen-dependent secretion of pro-tumourigenic cytokines, are well-known. Whether sex influences the efficacy and safety of immunotherapy is not known.

Methods: We performed a restricted maximum likelihood random effects meta-analysis of five phase III trials that evaluated immune checkpoint inhibitors (ICIs) in advanced HCC and reported overall survival (OS) hazard ratios (HRs) stratified by sex to evaluate sex-related differences in OS.

A comparison of the exposure system of glycidol-related chemicals on the formation of glycidol-hemoglobin adducts.

Glycidol fatty acid esters that are present in foods are degraded in vivo to the animal carcinogen glycidol, which binds to the -terminal valine of hemoglobin (Hb) to form -(2,3-dihydroxypropyl)valine (diHOPrVal) adducts. The existence of other chemicals that are converted to glycidol is unknown. To determine the effect of different exposure conditions on the formation of diHOPrVal adducts, several glycidol-related chemicals (3-monochloropropane-1,2-diol; 3-MCPD, epichlorohydrin, glyceraldehyde, acrylic acid, and 1,2-propanediol) were evaluated using in vitro and in vivo (single/repeated dose) methods.