A Phase 1/2 study of teclistamab, a humanized BCMA × CD3 bispecific Ab in Japanese patients with relapsed/refractory MM.

We characterized the safety and efficacy of the bispecific antibody teclistamab in Japanese patients with relapsed/refractory multiple myeloma (RRMM). Patients were pretreated with a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and anti-CD38 monoclonal antibody (mAb). The primary endpoint was frequency and type of treatment-emergent adverse events (TEAEs) in phase 1, and overall response rate (ORR; ≥ partial response [PR]) in phase 2.

Phase 1 Studies of the Anti-Tau Monoclonal Antibody JNJ-63733657 in Healthy Participants and Participants with Alzheimer's Disease.

Background: JNJ-63733657 (posdinemab) is a humanized IgG1/kappa monoclonal anti-phospho tau antibody that binds with high affinity to phosphorylated amino acid 217 (pT217) in the proline-rich domain. The parent molecule, PT3, was raised against Alzheimer's disease brain purified paired helical filament, and preclinical studies with the humanized version, JNJ-63733657, have demonstrated reductions in tau seeding. The results of the first-in-human clinical trial of JNJ-63733657 and a separate single ascending dose study in Japanese participants are presented.

Selective C-N Bond Cleavage in Unstrained Pyrrolidines Enabled by Lewis Acid and Photoredox Catalysis.

Cleavage of inert C-N bonds in unstrained azacycles such as pyrrolidine remains a formidable challenge in synthetic chemistry. To address this, we introduce an effective strategy for the reductive cleavage of the C-N bond in -benzoyl pyrrolidine, leveraging a combination of Lewis acid and photoredox catalysis. This method involves single-electron transfer to the amide, followed by site-selective cleavage at the C2-N bond.

Difference in Contractile Mechanisms between the Early and Sustained Components of Ionomycin-Induced Contraction in Rat Caudal Arterial Smooth Muscle.

We previously reported that the sustained component of contraction induced by depolarizing stimulation by high K concentration in rat caudal arterial smooth muscle involves a Ca-induced Ca sensitization mechanism whereby Ca entry through voltage-gated Ca channels activates proline-rich tyrosine kinase 2 (Pyk2), leading to activation of RhoA/Rho-associated kinase (ROCK). In the present study, we investigated a potential role for Pyk2-mediated RhoA/ROCK activation in contraction mediated by elevation of cytosolic free Ca concentration ([Ca]) induced by a Ca ionophore, ionomycin, rather than by depolarizing stimulation. Ionomycin (60 µM) induced slow and sustained contraction of rat caudal arterial smooth muscle due to influx of Ca.

Renal pelvic plasmacytoid subtype urothelial carcinoma accompanied with solitary mammary metastasis.

A 72-year-old female was referred to our institution for further evaluation of right renal tumor detected during work-up for macroscopic hematuria in other hospital. CT urography performed at our institution suggested renal pelvic tumor. Voiding cytology was atypical.

Right Carotid Artery Origin Compression Caused by Endovascular Repair for Kommerell Diverticulum Associated with a Right-Sided Aortic Arch.

Owing to the unique anatomical features, the endovascular repair for Kommerell diverticulum poses a surgical challenge. An 80-year-old, asymptomatic female with Kommerell diverticulum and associated right-sided aortic arch underwent an endovascular repair, consisting of an aortic arch endografting with a proximal extension, axillo-axillary crossover bypass, and right subclavian parallel endografting. An additional stent was promptly placed retrogradely at the right carotid artery origin as the completion aortography revealed an ostial occlusion.

Availability of dietary secoisolariciresinol diglucoside on borderline blood cholesterol level in men: a randomized, parallel, controlled, double-blinded clinical trial.

Borderline low-density lipoprotein cholesterol levels (120-139 mg/dl) increase the risk of cardiovascular disease. Therefore, the use of functional dietary nutrients is expected to control blood low-density lipoprotein cholesterol levels. This study aimed to evaluate the effect of dietary secoisolariciresinol diglucoside on blood cholesterol in healthy adults with borderline low-density lipoprotein cholesterol levels.

Effects of Oleanolic Acid Derived from Wine Pomace on Periodontopathic Bacterial Growth in Healthy Individuals: A Randomized Placebo-Controlled Study.

Periodontal disease is caused by oral pathogenic bacteria and is associated with systemic disease and frailty. Therefore, its prevention is crucial in extending healthy life expectancy. This study aimed to evaluate the effect of orally administered oleanolic acid, extracted from wine pomace, on periodontopathic bacterial growth in healthy individuals.

Late-stage benzenoid-to-troponoid skeletal modification of the cephalotanes exemplified by the total synthesis of harringtonolide.

Skeletal modifications enable elegant and rapid access to various derivatives of a compound that would otherwise be difficult to prepare. They are therefore a powerful tool, especially in the synthesis of natural products or drug discovery, to explore different natural products or to improve the properties of a drug candidate starting from a common intermediate. Inspired by the biosynthesis of the cephalotane natural products, we report here a single-atom insertion into the framework of the benzenoid subfamily, providing access to the troponoid congeners - representing the reverse of the proposed biosynthesis (i.

Small renal cell carcinoma accompanied by extensive inferior vena cava tumor thrombus diagnosed by percutaneous transvenous biopsy.

Introduction: Up to 10% of patients with renal cell carcinoma present with tumor thrombus in the inferior vena cava. We report that a case of small renal cell carcinoma with tumor thrombus extending above the diaphragm for which transvenous biopsy was performed for diagnosis.

Case Presentation: A 79-year-old man performed computed tomography to evaluate hepatic dysfunction, which revealed intravenous tumor extending above the diaphragm and a 15-mm-sized exophytic tumor in right kidney.

Pharmacokinetics and effect of maslinic acid with physical exercise on grip strength and trunk muscle mass in healthy Japanese individuals.

Age-related changes in physical function are closely associated with daily activity impairment among the elderly. Continuous maslinic acid intake may improve skeletal muscle mass; however, the concentration-dependent benefits of maslinic acid for physical functionality remain unclear. Therefore, we evaluated the bioavailability of maslinic acid and examined the effect of maslinic acid intake on skeletal muscle and quality of life in the healthy Japanese elderly.

Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus.

In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia (ADM), and intraepithelial neoplasia (PanIN), a precancerous lesion. The mechanisms underlying these changes remain unclear. The presence of enterovirus (EV) encoded-capsid protein 1 (VP1) and -2A protease (2A) and the innate immune responses of the pancreas were studied using immunohistochemistry and in situ hybridization in 12 SPIDDM and 19 non-diabetic control pancreases.

Synergistic antimicrobial potential of EGCG and fosfomycin against biofilms associated with endodontic infections.

Objective: This study aimed to evaluate the cytotoxicity and synergistic effect of epigallocatechin gallate (EGCG) and fosfomycin (FOSFO) on biofilms of oral bacteria associated with endodontic infections.

Methodology: This study determined minimum inhibitory and bactericidal concentration (MIC/MBC) and fractionated inhibitory concentration (FIC) of EGCG and FOSFO against Enterococcus faecalis, Actinomyces israelii, Streptococcus mutans, and Fusobacterium nucleatum. Monospecies and multispecies biofilms with those bacteria formed in polystyrene microplates and in radicular dentin blocks of bovine teeth were treated with the compounds and control chlorhexidine (CHX) and evaluated by bacterial counts and microscopy analysis.

[A Case of Rectal Cancer with Solitary Lymph Node Metastasis in the Stomach after Hepatectomy for Liver Metastasis].

A 44-year-old woman had undergone a laparoscopic low anterior resection and lymph node dissection for rectal cancer (pT4aN2aH0P0M0, pStage Ⅲc)in 20XX. Six months postoperatively, a CT scan revealed recurrent liver metastasis. She underwent surgery and adjuvant chemotherapy.

Relationship between atrial fibrillation and a liver fibrogenesis marker in patients with acute heart failure.

Background: Hemodynamic disturbance in heart failure (HF) induces extra-cardiac organ injury. Atrial fibrillation (AF) is common in patients with HF. The relationship between AF and organ injury in HF remains unclear.

Prognostic implications of post-discharge hemodynamic congestion assessed by peripheral venous pressure among patients discharged from acute heart failure.

Background: Congestion is a major cause of hospitalization for heart failure (HF). Peripheral venous pressure (PVP) strongly correlates with right atrial pressure. We recently reported that high PVP at discharge portends a poor prognosis in patients hospitalized for HF.

Cusatuzumab plus azacitidine in Japanese patients with newly diagnosed acute myeloid leukemia ineligible for intensive treatment.

We present the results of a phase 1 study that evaluated the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary disease response to cusatuzumab, a novel anti-CD70 monoclonal antibody, in combination with azacitidine, in newly diagnosed acute myeloid leukemia Japanese participants who were not candidates for intensive treatment. In this multicenter, single-arm study, six participants were enrolled and treated. Only in cycle 1, participants received cusatuzumab monotherapy on day 14.

Cloud service checklist for academic communities and customization for genome medical research.

In this paper, we present a cloud service checklist designed to help IT administrators or researchers in academic organizations select the most suitable cloud services. This checklist, which comprises items that we believe IT administrators or researchers in academic organizations should consider when they adopt cloud services, comprehensively covers the issues related to a variety of cloud services, including security, functionality, performance, and law. In response to the increasing demands for storage and computing resources in genome medical science communities, various guidelines for using resources operated by external organizations, such as cloud services, have been published by different academic funding agencies and the Japanese government.

[Early Experience with MRI-Ultrasound Fusion-Guided Prostate Biopsy in Our Institution].

A total of 100 patients were retrospectively analyzed with magnetic resonance imaging-ultrasonography (MRI-US) fusion biopsy(KOELIS, TRINITY®) at our institution between October 2019 and May 2020. The median patient age was 71 years, median prostate specific antigen (PSA) level was 7.4 ng/ml, and median PSA-density was 0.

Ciltacabtagene autoleucel in patients with relapsed/refractory multiple myeloma: CARTITUDE-1 (phase 2) Japanese cohort.

Chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen have shown positive responses in patients with multiple myeloma (MM). The phase 2 portion of the CARTITUDE-1 study of ciltacabtagene autoleucel (cilta-cel) included a cohort of Japanese patients with relapsed/refractory MM. Following a conditioning regimen of cyclophosphamide (300 mg/m ) and fludarabine (30 mg/m ), patients received a single cilta-cel infusion at a target dose of 0.

Association of peripheral venous pressure with adverse post-discharge outcomes in patients with acute heart failure: a prospective cohort study.

Aims: Congestion is the major cause of hospitalization for heart failure (HF). Traditional bedside assessment of congestion is limited by insufficient accuracy. Peripheral venous pressure (PVP) has recently been shown to accurately predict central venous congestion.