Risk scoring system for evaluating pathological upstaging after radical nephroureterectomy for upper tract urothelial carcinoma: A multicenter study in Japan.

Objectives: Accurate preoperative staging of upper tract urothelial carcinoma is often difficult. Therefore, we aimed to investigate the preoperative factors associated with pathological upstaging in patients with upper tract urothelial carcinoma undergoing radical nephroureterectomy and to develop a risk-scoring system to assess pathological upstaging.

Methods: This retrospective study enrolled 386 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy at Tottori University Hospital and affiliated hospitals between January 2015 and December 2021.

Long-term in vivo performance of silicone membrane lungs coated with novel methacryloyloxyethyl phosphorylcholine polymers: A pilot study.

Background: This study was designed to evaluate the long-term durability, oxygenation, and pressure loss of newly developed, methacryloyloxyethyl phosphorylcholine (MPC)-polymer-coated, nonporous silicone hollow fiber-membrane lungs in vivo using a pulmonary artery-to-left-atrium paracorporeal configuration.

Methods: An extracorporeal circuit from the pulmonary artery (device inflow) to the left atrium (device outflow) was established using dedicated composite vascular grafts in three healthy female goats for the prototype lung testing.

Results: Duration of testing the prototype lungs was 52, 57, or 100 days.

The Benefits of Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma Require at Least Three Cycles.

Background: Upper urinary tract urothelial carcinoma (UTUC) is uncommon. In advanced cases, radical nephroureterectomy (RNU) alone is not curative, and recurrence and metastasis are likely to occur. Adjuvant chemotherapy (AC) is an evidence-based treatment.

Preoperative risk stratification models after radical cystectomy for bladder cancer: A multi-center study.

Objective: We investigated preoperative patient factors associated with prognosis in 263 bladder cancer (BC) patients undergoing radical cystectomy (RC). We also developed new risk stratification models for prognosis.

Methods: This retrospective study included patients treated at Tottori University Hospital and affiliated hospitals between January 2010 and December 2019.

Stability Enhancement by Hydrophobic Anchoring and a Cross-Linked Structure of a Phospholipid Copolymer Film for Medical Devices.

Surface modification using zwitterionic 2-methacryloyloxyethylphosphorylcholine (MPC) polymers is one of the most reasonable ways to prepare medical devices that can suppress undesired biological reactions such as blood coagulation. Usable MPC polymers are hydrophilic and water soluble, and their surface modification strategy involves exploiting the copolymer structures by adding physical or chemical bonding moieties. In this study, we developed copolymers composed of MPC, hydrophobic anchoring moiety, and chemical cross-linking unit to clarify the role of hydrophobic interactions in achieving biocompatible and long-term stable coatings.

Synthesis, activity, and their relationships of 2,4-diaminonicotinamide derivatives as EGFR inhibitors targeting C797S mutation.

The C797S mutation is one of the major factors behind resistance to the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Herein, we describe the discovery of the 2,4-diaminonicotinamide derivative 5j, which shows potent inhibitory activity against EGFR del19/T790M/C797S and L858R/T790M/C797S. We also report the structure-activity relationship of the 2,4-diaminonicotinamide derivatives and the co-crystal structure of 5j and EGFR del19/T790M/C797S.

Design of a hybrid left ventricular assist device with a new wireless charging system.

Background: The objective of this study was to design a new wireless left ventricular assist device (LVAD) that can be charged without using a conventional transcutaneous energy transfer system (TETS).

Methods: Our new wireless LVAD was a hybrid pump operating in two different modes: magnetic and electric modes. The pump was driven wirelessly by extracorporeal rotating magnets in magnetic mode, whereas it was driven by electricity provided by an intracorporeal battery in electric mode.

Cardiovascular adverse reactions associated with escitalopram in patients with underlying cardiovascular diseases: a systematic review and meta-analysis.

Background: Despite the anticipated efficacy of escitalopram in treating depression and anxiety in individuals with preexisting cardiovascular conditions, persistent concerns regarding its adverse effects have emerged. In this systematic review, we aimed to evaluate the cardiovascular safety profile of escitalopram compared with that of placebo in patients with underlying cardiovascular disease.

Methods: We used a predefined search strategy in PubMed, Cochrane Central Register of Controlled Trials, Embase, International Clinical Trials Registry Platform, and ClinicalTrials.

Rattractor-Instant guidance of a rat into a virtual cage using the deep brain stimulation.

We developed "Rattractor" (rat attractor), a system to apply electrical stimuli to the deep brain of a rat as it stays in a specified region or a virtual cage to demonstrate an instant electrophysiological feedback guidance for animals. Two wire electrodes were implanted in the brains of nine rats. The electrodes targeted the medial forebrain bundle (MFB), which is a part of the reward system in the deep brain.

Impact of Hyper- and Hypo-Uricemia on Kidney Function.

Uric acid (UA) forms monosodium urate (MSU) crystals to exert proinflammatory actions, thus causing gout arthritis, urolithiasis, kidney disease, and cardiovascular disease. UA is also one of the most potent antioxidants that suppresses oxidative stress. Hyper andhypouricemia are caused by genetic mutations or polymorphism.

Design of an Innovative Wireless Left Ventricular Assist Device Driven by either Extracorporeal Magnets or an Intracorporeal Battery Pack.

This study aimed to design a new wireless left ventricular assist device (LVAD) that solved the driveline problem of current LVADs and the heat problem of the transcutaneous energy transfer system (TETS). Our new wireless LVAD consisted of two blood pumps capable of driving using extracorporeal magnets and an intracorporeal battery pack. When one pump was driven, the other pump was stopped.

Discovery of DS-9300: A Highly Potent, Selective, and Once-Daily Oral EP300/CBP Histone Acetyltransferase Inhibitor.

Histone acetylation is a post-translational modification of histones that is catalyzed by histone acetyltransferases (HATs) and plays an essential role in cellular processes. The HAT domain of EP300/CBP has recently emerged as a potential drug target for cancer therapy. Here, we describe the identification of the novel, highly potent, and selective EP300/CBP HAT inhibitor DS-9300.

Characterization of Urate Metabolism and Complications of Patients with Renal Hypouricemia.

Objective Both renal hypouricemia (RHU) and gout are associated with renal dysfunction and urolithiasis. The difference in renal complications associated with RHU and gout, however, has not been studied. We characterized the urate metabolism and complications of patients with RHU and compared them with patients with gout.

Blind Speech Watermarking Method with Frame Self-Synchronization Based on Spread-Spectrum Using Linear Prediction Residue.

State-of-the-art speech watermarking techniques enable speech signals to be authenticated and protected against any malicious attack to ensure secure speech communication. In general, reliable speech watermarking methods must satisfy four requirements: inaudibility, robustness, blind-detectability, and confidentiality. We previously proposed a method of non-blind speech watermarking based on direct spread spectrum (DSS) using a linear prediction (LP) scheme to solve the first two issues (inaudibility and robustness) due to distortion by spread spectrum.

Discovery of EP300/CBP histone acetyltransferase inhibitors through scaffold hopping of 1,4-oxazepane ring.

EP300 and its paralog CBP play an important role in post-translational modification as histone acetyltransferases (HATs). EP300/CBP inhibition has been gaining attention as an anticancer treatment target in recent years. Herein, we describe the identification of a novel, highly selective EP300/CBP inhibitor, compound 11 (DS17701585), by scaffold hopping and structure-based optimization of a high-throughput screening hit 1.

Apathy in Alzheimer's Disease Correlates with the Dopamine Transporter Level in the Caudate Nuclei.

Introduction: Apathy is a common neuropsychiatric symptom in patients with Alzheimer's disease (AD). The striatal binding potential (BP) of I-FP-CIT (-δ-fluoropropyl-2β-carbomethoxy-3β-[4-iodophenyl]tropane) single-photon emission computed tomography (SPECT) is correlated with the degree of apathy in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). This study aimed to determine if dopaminergic activity in the basal ganglia is associated with the development of apathy in AD.

Xp11.2 translocation renal cell carcinoma with TFE3 gene fusion in the elderly: case report and literature review.

A 68-year-old man was followed up with chronic kidney disease. Follow-up CT incidentally detected a tumor at the left kidney and multiple small nodular shadows in the lungs bilaterally. The patient underwent needle biopsy and was diagnosed with Xp11.

U.S. Phase I First-in-human Study of Taletrectinib (DS-6051b/AB-106), a ROS1/TRK Inhibitor, in Patients with Advanced Solid Tumors.

Purpose: Taletrectinib (DS-6051b/AB-106) is an oral, tyrosine kinase inhibitor of ROS1 and NTRK with potent preclinical activity against G2032R solvent-front mutation among others. We report the first-in-human U.S.

Villous adenoma of the urachus obscuring urachal adenocarcinoma: A case report.

We report a case of a 78-year-old woman with a urachal tumor of the bladder wall. We performed a biopsy and revealed the tumor as a villous adenoma. We excised the tumor by partial cystectomy together with the umbilical ligament, because it was possible there was a co-existing malignancy.

Spontaneous regression of metastatic renal cell carcinoma after cytoreductive nephrectomy: A case report.

We herein report a case involving a 59-year-old man with right lung and mediastinal lymph node metastases from renal cell carcinoma. After cytoreductive nephrectomy without neoadjuvant therapy, he achieved spontaneous regression. The regression was maintained 3 years after the operation.

Quizartinib, a selective FLT3 inhibitor, maintains antileukemic activity in preclinical models of RAS-mediated midostaurin-resistant acute myeloid leukemia cells.

internal tandem duplication (ITD) mutations are associated with poor prognosis in patients with acute myeloid leukemia (AML). In this preclinical study, we characterized the binding affinity and selectivity of quizartinib, a small-molecule inhibitor of FLT3, and AC886, the active metabolite of quizartinib, compared with those of other FLT3 inhibitors. Selectivity profiling against >400 kinases showed that quizartinib and AC886 were highly selective against FLT3.

DS-1205b, a novel selective inhibitor of AXL kinase, blocks resistance to EGFR-tyrosine kinase inhibitors in a non-small cell lung cancer xenograft model.

The AXL receptor tyrosine kinase is involved in signal transduction in malignant cells. Recent studies have shown that the AXL upregulation underlies epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) resistance in EGFR-mutant non-small cell lung cancer (NSCLC). In this study, we investigated the effect of DS-1205b, a novel and selective inhibitor of AXL, on tumor growth and resistance to EGFR TKIs.

The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models.

ROS1 gene rearrangement was observed in around 1-2 % of NSCLC patients and in several other cancers such as cholangiocarcinoma, glioblastoma, or colorectal cancer. Crizotinib, an ALK/ROS1/MET inhibitor, is highly effective against ROS1-rearranged lung cancer and is used in clinic. However, crizotinib resistance is an emerging issue, and several resistance mechanisms, such as secondary kinase-domain mutations (e.